The present study was aimed at identifying novel proteins in endometrial cancer (EC), employing proteomic analysis of tissues obtained after surgery. A differential MS-based proteomic analysis was conducted from whole tissues dissected from biopsies from post-menopausal women, histologically confirmed as endometrial cancer (two endometrioid and two serous; n = 4) or normal atrophic endometrium (n = 4), providing 888 differentially expressed proteins with 246 of these previously documented elsewhere as expressed in EC and 372 proteins not previously demonstrated to be expressed in EC but associated with other types of cancer. Additionally, 33 proteins not recorded previously in PubMed as being expressed in any forms of cancer were also identified, with only 26 of these proteins having a publication associated with their expression patterns or putative functions. The putative functions of the 26 proteins (GRN, APP, HEXA, CST3, CAD, QARS, SIAE, WARS, MYH8, CLTB, GOLIM4, SCARB2, BOD1L1, C14orf142, C9orf142, CCDC13, CNPY4, FAM169A, HN1L, PIGT, PLCL1, PMFBP1, SARS2, SCPEP1, SLC25A24 and ZC3H4) in other tissues point towards and provide a basis for further investigation of these previously unrecognised novel EC proteins. The developmental biology, disease, extracellular matrix, homeostatic, immune, metabolic (both RNA and protein), programmed cell death, signal transduction, molecular transport, transcriptional networks and as yet uncharacterised pathways indicate that these proteins are potentially involved in endometrial carcinogenesis and thus may be important in EC diagnosis, prognostication and treatment and thus are worthy of further investigation.

1. Coll-de la Rubia, E., Martinez-Garcia, E., Dittmar, G., Gil-Moreno, A., Cabrera, S., & Colas, E. (2020). Prognostic biomarkers in endometrial cancer: A systematic review and meta-analysis. Journal of Clinical Medicine, 9(6), Article 1900. https://doi.org/10.3390/jcm9061900
2. Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., Murray, T., & Thun, M. J. (2008). Cancer statistics, 2008. CA: A Cancer Journal for Clinicians, 58(2), 71–96. https://doi.org/10.3322/CA.2007.0010
3. Ricceri, F., Giraudo, M. T., Fasanelli, F., Milanese, D., Sciannameo, V., Fiorini, L., & Sacerdote, C. (2017). Diet and endometrial cancer: A focus on the role of fruit and vegetable intake, Mediterranean diet and dietary inflammatory index in the endometrial cancer risk. BMC Cancer, 17(1), Article 757. https://doi.org/10.1186/s12885-017-3754-y
4. Fiorelli, J. L., Herzog, T. J., Wright, J. D. (2008). Current treatment strategies for endometrial cancer. Expert Review of Anticancer Therapy, 8(7), 1149–1157. https://doi.org/10.1586/14737140.8.7.1149
5. Clarke, M. A., Long, B. J., Del Mar Morillo, A., Arbyn, M., Bakkum-Gamez, J. N., & Wentzensen, N. (2018). Association of endometrial cancer risk with postmenopausal bleeding in women: A systematic review and meta-analysis. JAMA Internal Medicine, 178(9), 1210–1222. https://doi.org/10.1001/jamainternmed.2018.3459
6. Faber, M. T., Frederiksen, K., Jensen, A., Aarslev, P. B., & Kjaer, S. K. (2017). Time trends in the incidence of hysterectomy-corrected overall, type 1 and type 2 endometrial cancer in Denmark 1978–2014. Gynecologic Oncology, 146(2), 359–367. https://doi.org/10.1016/j.ygyno.2017.05.021
7. Onstad, M. A., Schmandt, R. E., & Lu, K. H. (2016). Addressing the role of obesity in endometrial cancer risk, prevention, and treatment. Journal of Clinical Oncology, 34(35), 4225–4230. https://doi.org/10.1212/JCO.2016.69.4638
8. von Gruenigen, V. E., Gil, K. M., Frasure, H. E., Jenison, E. L., & Hopkins, M. P. (2005). The impact of obesity and age on quality of life in gynecologic surgery. American Journal of Obstetrics and Gynecology, 193(4), 1369–1375. https://doi.org/10.1016/j.ajog.2005.03.060
9. Aune, D., Navarro Rosenblatt, D. A., Chan, D. S., Vingeliene, S., Abar, L., Vieira, A. R., Greenwood, D. C., Bandera, E. V., & Norat, T. (2015). Anthropometric factors and endometrial cancer risk: A systematic review and dose-response meta-analysis of prospective studies. Annals of Oncology, 26(8), 1635–1648. https://doi.org/10.1093/annonc/mdv142
10. Sorosky, J. I. (2012). Endometrial cancer. Obstetrics & Gynecology, 120(2), 383–397. https://doi.org/10.1097/AOG.0b013e3182605b14
11. Urick, M. E., & Bell, D. W. (2019). Clinical actionability of molecular targets in endometrial cancer. Nature Reviews Cancer, 19(9), 510–521. https://doi.org/10.1038/s41568-019-0165-4
12. Blair, A. R., & Casas, C. M. (2009). Gynecologic cancers. Primary Care: Clinics in Office Practice, 36(1), 115–130. https://doi.org/10.1016/j.pop.2008.10.003
13. Ayakannu, T., Taylor, A. H., Marczylo, T. H., Maccarrone, M., & Konje, J. C. (2019). Identification of novel predictive biomarkers for endometrial malignancies: N-acylethanolamines. Frontiers in Oncology, 9, Article 430. https://doi.org/10.3389/fonc.2019.00430
14. Travaglino, A., Raffone, A., Saccone, G., Insabato, L., Mollo, A., De Placido, G., & Zullo, F. (2019). Immunohistochemical predictive markers of response to conservative treatment of endometrial hyperplasia and early endometrial cancer: A systematic review. Acta Obstetricia et Gynecologica Scandinavica, 98(9), 1086–1099. https://doi.org/10.1111/aogs.13591
15. Lacey, J. V., Jr., & Chia, V. M. (2009). Endometrial hyperplasia and the risk of progression to carcinoma. Maturitas, 63(1), 39–44. https://doi.org/10.1016/j.maturitas.2009.02.005
16. Alkhas, A., Hood, B. L., Oliver, K., Teng, P. N., Oliver, J., Mitchell, D., Hamilton, C. A., Maxwell, G. L., & Conrads, T. P. (2011). Standardization of a sample preparation and analytical workflow for proteomics of archival endometrial cancer tissue. Journal of Proteome Research, 10(11), 5264–5271. https://doi.org/10.1021/pr200676a
17. Attarha, S., Mints, M., Andersson, S., & Souchelnytskyi, S. (2011). Endometrial cancer and application of proteomics. Experimental Oncology, 33(3), 174–177.
18. Baak, J. P., Path, F. R., Hermsen, M. A., Meijer, G., Schmidt, J., & Janssen, E. A. (2003). Genomics and proteomics in cancer. European Journal of Cancer, 39(9), 1199–1215. https://doi.org/10.1016/S0959-8049(03)00216-7
19. Dube, V., Grigull, J., DeSouza, L. V., Ghanny, S., Colgan, T. J., Romaschin, A. D., & Siu, K. W. (2007). Verification of endometrial tissue biomarkers previously discovered using mass spectrometry-based proteomics by means of immunohistochemistry in a tissue microarray format. Journal of Proteome Research, 6(7), 2648–2655. https://doi.org/10.1021/pr070044o
20. Kacerovsky, M., & Tosner, J. (2009). Proteomics and biomarkers for detection of endometrial carcinoma. Ceska Gynekologie, 74(4), 274–278.
21. Li, Z., Min, W., Huang, C., Bai, S., Tang, M., & Zhao, X. (2010). Proteomics-based approach identified differentially expressed proteins with potential roles in endometrial carcinoma. International Journal of Gynecological Cancer, 20(1), 9–15. https://doi.org/10.1111/IGC.0b013e3181c4a034
22. Martinez-Garcia, E., Lesur, A., Devis, L., Cabrera, S., Matias-Guiu, X., Hirschfeld, M., Asberger, J., van Oostrum, J., Casares de Cal, M. L. A., Gomez-Tato, A., ... & Colas, E. (2017). Targeted proteomics identifies proteomic signatures in liquid biopsies of the endometrium to diagnose endometrial cancer and assist in the prediction of the optimal surgical treatment. Clinical Cancer Research, 23(21), 6458–6467. https://doi.org/10.1158/1078-0432.CCR-17-0474
23. Mittal, P., Klingler-Hoffmann, M., Arentz, G., Zhang, C., Kaur, G., Oehler, M. K., & Hoffmann, P. (2016). Proteomics of endometrial cancer diagnosis, treatment, and prognosis. Proteomics – Clinical Applications, 10(3), 217–229. https://doi.org/10.1002/prca.201500057
24. Van Gorp, T., Cadron, I., & Vergote, I. (2011). The utility of proteomics in gynecologic cancers. Current Opinion in Obstetrics and Gynecology, 23(1), 3–7. https://doi.org/10.1097/GCO.0b013e3283413ef5
25. Yi, Z., Jingting, C., & Yu, Z. (2009). Proteomics reveals protein profile changes in cyclooxygenase-2 inhibitor-treated endometrial cancer cells. International Journal of Gynecological Cancer, 19(3), 326–333. https://doi.org/10.1111/IGC.0b013e31819c5c76
26. Kandoth, C., Schultz, N., Cherniack, A. D., Akbani, R., Liu, Y., Shen, H., Robertson, A. G., Pashtan, I., Shen, R., Benz, C. C., ... & Cancer Genome Atlas Research Network. (2013). Integrated genomic characterization of endometrial carcinoma. Nature, 497(7447), 67–73. https://doi.org/10.1038/nature12113
27. Dalman, M. R., Deeter, A., Nimishakavi, G., & Duan, Z. H. (2012). Fold change and p-value cutoffs significantly alter microarray interpretations. BMC Bioinformatics, 13(Suppl 2), S11. https://doi.org/10.1186/1471-2105-13-S2-S11
28. Ayakannu, T., Taylor, A. H., Bari, M., Mastrangelo, N., Maccarrone, M., & Konje, J. C. (2019). Expression and function of the endocannabinoid modulating enzymes Fatty Acid Amide Hydrolase and N-Acylphosphatidylethanolamine-Specific Phospholipase D in endometrial carcinoma. Frontiers in Oncology, 9, Article 1363. https://doi.org/10.3389/fonc.2019.01363
29. Turapov, O. A., Mukamolova, G. V., Bottrill, A. R., & Pangburn, M. K. (2008). Digestion of native proteins for proteomics using a thermocycler. Analytical Chemistry, 80(15), 6093–6099. https://doi.org/10.1021/ac800569p
30. Speicher, K. D., Kolbas, O., Harper, S., & Speicher, D. W. (2000). Systematic analysis of peptide recoveries from in-gel digestions for protein identifications in proteome studies. Journal of Biomolecular Techniques, 11(2), 74–86.
31. Moiseeva, T. N., Bottrill, A., Melino, G., & Barlev, N. A. (2013). DNA damage-induced ubiquitylation of proteasome controls its proteolytic activity. Oncotarget, 4(8), 1338–1348. https://doi.org/10.18632/oncotarget.1218
32. Keller, A., Nesvizhskii, A. I., Kolker, E., & Aebersold, R. (2002). Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search. Analytical Chemistry, 74(20), 5383–5392. https://doi.org/10.1021/ac0201833
33. Jassal, B., Matthews, L., Viteri, G., Gong, C., Lorente, P., Fabregat, A., Sidiropoulos, K., Cook, J., Gillespie, M., Haw, R., ... & D'Eustachio, P. (2020). The reactome pathway knowledgebase. Nucleic Acids Research, 48(D1), D498–D503. https://doi.org/10.1093/nar/gkz1031
34. Zaino, R. J., Kurman, R. J., Diana, K. L., & Morrow, C. P. (1995). The utility of the revised International Federation of Gynecology and Obstetrics histologic grading of endometrial adenocarcinoma using a defined nuclear grading system: A Gynecologic Oncology Group study. Cancer, 75(1), 81–86. https://doi.org/10.1002/1097-0142(19950101)75:1<81::AID-CNCR2820750114>3.0.CO;2-G
35. Dou, Y., Kawaler, E. A., Cui Zhou, D., Gritsenko, M. A., Huang, C., Blumenberg, L., Karpova, A., Petyuk, V. A., Savage, S. R., Satpathy, S., ... & Zhang, B. (2020). Proteogenomic characterization of endometrial carcinoma. Cell, 180(4), 729–748.e26. https://doi.org/10.1016/j.cell.2020.01.026
36. Deb, B., Sengupta, P., Sambath, J., & Kumar, P. (2020). Bioinformatics analysis of global proteomic and phosphoproteomic data sets revealed activation of NEK2 and AURKA in cancers. Biomolecules, 10(2), Article 237. https://doi.org/10.3390/biom10020237
37. Ceylan, Y., Akpinar, G., Doger, E., Kasap, M., Guzel, N., Karaosmanoglu, K., Kopuk, S. Y., & Yucesoy, I. (2020). Proteomic analysis in endometrial cancer and endometrial hyperplasia tissues by 2D-DIGE technique. Journal of Gynecology Obstetrics and Human Reproduction, 49(2), Article 101652. https://doi.org/10.1016/j.jogoh.2019.101652
38. Acland, M., Arentz, G., Mussared, M., Whitehead, F., Hoffmann, P., Klingler-Hoffmann, M., & Oehler, M. K. (2020). Proteomic analysis of pre-invasive serous lesions of the endometrium and fallopian tube reveals their metastatic potential. Frontiers in Oncology, 10, Article 523989. https://doi.org/10.3389/fonc.2020.523989
39. Njoku, K., Chiasserini, D., Whetton, A.D., & Crosbie, E. J. (2019). Proteomic biomarkers for the detection of endometrial cancer. Cancers, 11(10), Article 1572. https://doi.org/10.3390/cancers11101572
40. Liu, J., Mei, J., Li, S., Wu, Z., & Zhang, Y. (2020). Establishment of a novel cell cycle-related prognostic signature predicting prognosis in patients with endometrial cancer. Cancer Cell International, 20(1), Article 329. https://doi.org/10.1186/s12935-020-01428-1
41. Degez, M., Caillon, H., Chauvire-Drouard, A., Leroy, M., Lair, D., Winer, N., & Thubert, T. (2020). Endometrial cancer: A systematic review of HE4, REM and REM-B. Clinica Chimica Acta, 515, 27–36. https://doi.org/10.1016/j.cca.2020.12.025
42. Gasiorowska, E., Magnowska, M., Izycka, N., Warchol, W., & Nowak-Markwitz, E. (2016). The role of HE4 in differentiating benign and malignant endometrial pathology. Ginekologia Polska, 87(4), 260–264. https://doi.org/10.17772/gp/62208
43. Galgano, M. T., Hampton, G. M., & Frierson, H. F., Jr. (2006). Comprehensive analysis of HE4 expression in normal and malignant human tissues. Modern Pathology, 19(6), 847–853. https://doi.org/10.1038/modpathol.3800596
44. Ponnambalam, S., Jackson, A. P., LeBeau, M. M., Pravtcheva, D., Ruddle, F. H., Alibert, C., & Parham, P. (1994). Chromosomal location and some structural features of human clathrin light-chain genes (CLTA and CLTB). Genomics, 24(3), 440–444. https://doi.org/10.1006/geno.1994.1651
45. Holzer, I., Machado Weber, A., Marshall, A., Freis, A., Jauckus, J., Strowitzki, T., & Germeyer, A. (2020). GRN, NOTCH3, FN1, and PINK1 expression in eutopic endometrium-potential biomarkers in the detection of endometriosis—A pilot study. Journal of Assisted Reproduction and Genetics, 37(11), 2723–2732. https://doi.org/10.1007/s10815-020-01934-7
46. Sosa, L. J., Cáceres, A., Dupraz, S., Oksdath, M., Quiroga, S., & Lorenzo, A. (2017). The physiological role of the amyloid precursor protein as an adhesion molecule in the developing nervous system. Journal of Neurochemistry, 143(1), 11–29. https://doi.org/10.1111/jnc.14122
47. Iuvone, T., De Filippis, D., Di Spiezio Sardo, A., D’Amico, A., Simonetti, S., Sparice, S., Esposito, G., Bifulco, G., Insabato, L., Nappi, C., ... & Petrosino, S. (2008). Selective CB2 up-regulation in women affected by endometrial inflammation. Journal of Cellular and Molecular Medicine, 12(2), 661–670. https://doi.org/10.1111/j.1582-4934.2007.00100.x
48. Erikson, D. W., Barragan, F., Piltonen, T. T., Chen, J. C., Balayan, S., Irwin, J. C., & Giudice, L. C. (2017). Stromal fibroblasts from perimenopausal endometrium exhibit a different transcriptome than those from the premenopausal endometrium. Biology of Reproduction, 97(3), 387–399. https://doi.org/10.1093/biolre/iox090
49. Lindsey-Boltz, L. A., Wauson, E. M., Graves, L. M., & Sancar, A. (2004). The human Rad9 checkpoint protein stimulates the carbamoyl phosphate synthetase activity of the multifunctional protein CAD. Nucleic Acids Research, 32(15), 4524–4530. https://doi.org/10.1093/nar/gkh782
50. Davis, A. M., Mao, J., Naz, B., Kohl, J. A., & Rosenfeld, C. S. (2008). Comparative effects of estradiol, methyl-piperidino-pyrazole, raloxifene, and ICI 182 780 on gene expression in the murine uterus. Journal of Molecular Endocrinology, 41(4), 205–217. https://doi.org/10.1677/JME-08-0050
51. Herndon, C. N., Aghajanova, L., Balayan, S., Erikson, D., Barragan, F., Goldfien, G., Vo, K. C., Hawkins, S., & Giudice, L. C. (2016). Global transcriptome abnormalities of the eutopic endometrium from women with adenomyosis. Reproductive Sciences, 23(10), 1289–1303. https://doi.org/10.1177/1933719116654999
52. Nguyen, T. T. T., Yoon, H. K., Kim, Y. T., Choi, Y. H., Lee, W. K., & Jin, M. (2020). Tryptophanyl-tRNA Synthetase 1 signals activate TREM-1 via TLR2 and TLR4. Biomolecules, 10(9), Article 1283. https://doi.org/10.3390/biom10091283
53. Houshdaran, S., Oke, A. B., Fung, J. C., Vo, K. C., Nezhat, C., & Giudice, L. C. (2020). Steroid hormones regulate genome-wide epigenetic programming and gene transcription in human endometrial cells with marked aberrancies in endometriosis. PLoS Genetics, 16(6), Article e1008601. https://doi.org/10.1371/journal.pgen.1008601
54. Tapia-Pizarro, A., Figueroa, P., Brito, J., Marín, J. C., Munroe, D. J., & Croxatto, H. B. (2014). Endometrial gene expression reveals compromised progesterone signaling in women refractory to embryo implantation. Reproductive Biology and Endocrinology, 12, Article 92. https://doi.org/10.1186/1477-7827-12-92
55. Guo, H., Zhang, J., Zhang, X., Wang, Y., Yu, H., Yin, X., Li, J., Du, P., Plumas, J., Chaperot, L., ... & Cao, W. (2015). SCARB2/LIMP-2 regulates IFN production of plasmacytoid dendritic cells by mediating endosomal translocation of TLR9 and nuclear translocation of IRF7. The Journal of Immunology, 194(10), 4737–4749. https://doi.org/10.4049/jimmunol.1402321
56. García, P., Rosa, L., Vargas, S., Weber, H., Espinoza, J. A., Suárez, F., Romero-Calvo, I., Elgueta, N., Rivera, V., Nervi, B., ... & Roa, J. C. (2020). Hippo-YAP1 is a prognosis marker and potentially targetable pathway in advanced gallbladder cancer. Cancers, 12(4), Article 778. https://doi.org/10.3390/cancers12040778
57. Wan, L. C., Maisonneuve, P., Szilard, R. K., Lambert, J. P., Ng, T. F., Manczyk, N., Huang, H., Laister, R., Caudy, A. A., Gingras, A. C., ... & Durocher, D. (2017). Proteomic analysis of the human KEOPS complex identifies C14ORF142 as a core subunit homologous to yeast Gon7. Nucleic Acids Research, 45(2), 805–817. https://doi.org/10.1093/nar/gkw1181
58. Kaplan, A. R., & Glazer, P. M. (2020). Pharmacological methods to transcriptionally modulate double-strand break DNA repair. International Review of Cell and Molecular Biology, 354, 187–213. https://doi.org/10.1016/bs.ircmb.2020.02.004
59. Staples, C. J., Myers, K. N., Beveridge, R. D., Patil, A. A., Howard, A. E., Barone, G., Lee, A. J., Swanton, C., Howell, M., Maslen, S., ... & Collis, S. J. (2014). Ccdc13 is a novel human centriolar satellite protein required for ciliogenesis and genome stability. Journal of Cell Science, 127(13), 2910–2919. https://doi.org/10.1242/jcs.147710
60. Hodge, J. C., Park, P. J., Dreyfuss, J. M., Assil-Kishawi, I., Somasundaram, P., Semere, L. G., Quade, B. J., Lynch, A. M., Stewart, E. A., & Morton, C. C. (2009). Identifying the molecular signature of the interstitial deletion 7q subgroup of uterine leiomyomata using a paired analysis. Genes, Chromosomes and Cancer, 48(10), 865–885. https://doi.org/10.1002/gcc.20691
61. Yerushalmi, G. M., Salmon-Divon, M., Ophir, L., Yung, Y., Baum, M., Coticchio, G., Fadini, R., Mignini-Renzini, M., Dal Canto, M., Machtinger, R., ... & Hourvitz, A. (2018). Characterization of the miRNA regulators of the human ovulatory cascade. Scientific Reports, 8, Article 15605. https://doi.org/10.1038/s41598-018-33827-0
62. Shen, H. R., Qiu, L. H., Zhang, Z.Q., Qin, Y.Y., Cao, C., & Di, W. (2013). Genome-wide methylated DNA immunoprecipitation analysis of patients with polycystic ovary syndrome. PLoS ONE, 8(5), Article e64801. https://doi.org/10.1371/journal.pone.0064801
63. Muter, J., Brighton, P. J., Lucas, E. S., Lacey, L., Shmygol, A., Quenby, S., Blanks, A. M., & Brosens, J. J. (2016). Progesterone-dependent induction of Phospholipase C-Related Catalytically Inactive Protein 1 (PRIP-1) in decidualizing human endometrial stromal cells. Endocrinology, 157(7), 2883–2893. https://doi.org/10.1210/en.2016-1070
64. Lu, Z., Hardt, J., & Kim, J. J. (2008). Global analysis of genes regulated by HOXA10 in decidualization reveals a role in cell proliferation. Molecular Human Reproduction, 14(6), 357–366. https://doi.org/10.1093/molehr/ga_n025
65. Kumar, P., Tathe, P., Chaudhary, N., & Maddika, S. (2019). PPM1G forms a PPP-type phosphatase holoenzyme with B56δ that maintains adherens junction integrity. EMBO Reports, 20(5), Article e46965. https://doi.org/10.15252/embr.201846965
66. Bresch, A. M., Yerich, N., Wang, R., & Sperry, A. O. (2020). The PP1 regulator PPP1R2 coordinately regulates AURKA and PP1 to control centrosome phosphorylation and maintain central spindle architecture. BMC Molecular and Cell Biology, 21, Article 84. https://doi.org/10.1186/s12860-020-00330-y
67. Holman, K. M., Puppala, A. K., Lee, J. W., & Lee, H., & Simonović, M. (2017). Insights into substrate promiscuity of human seryl-tRNA synthetase. RNA, 23(11), 1685–1699. https://doi.org/10.1261/rna.062257.117
68. Lübke, T., Lobel, P., & Sleat, D. E. (2009). Proteomics of the lysosome. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1793(4), 625–635. https://doi.org/10.1016/j.bbamcr.2008.10.001
69. Cai, H., Zhu, X. X., Li, Z. F., Zhu, Y. P., & Lang, J. H. (2018). MicroRNA dysregulation and steroid hormone receptor expression in uterine tissues of rats with endometriosis during the implantation window. Chinese Medical Journal, 131(18), 2193–2204. https://doi.org/10.4103/0366-6999.240861
70. Zhou, D., Wu, Y., Wang, S., Li, J., & Luan, J. (2020). Harnessing noncoding RNA-based macrophage polarization: Emerging therapeutic opportunities for fibrosis. Immunity, Inflammation and Disease, 8(4), 793–806. https://doi.org/10.1002/iid3.348
71. Hung, K. E., & Yu, K. H. (2010). Proteomic approaches to cancer biomarkers. Gastroenterology, 138(1), 46–51.e41. https://doi.org/10.1053/j.gastro.2009.11.028
72. Makawita, S., & Diamandis, E. P. (2010). The bottleneck in the cancer biomarker pipeline and protein quantification through mass spectrometry-based approaches: Current strategies for candidate verification. Clinical Chemistry, 56(2), 212–222. https://doi.org/10.1373/clinchem.2009.127068
73. Negishi, A., Ono, M., Handa, Y., Kato, H., Yamashita, K., Honda, K., Shitashige, M., Satow, R., Sakuma, T., Kuwabara, H., ... & Hirohashi, S. (2009). Large-scale quantitative clinical proteomics by label-free liquid chromatography and mass spectrometry. Cancer Science, 100(3), 514–519. https://doi.org/10.1111/j.1349-7006.2008.01064.x
74. Scherl, A., Francois, P., Converset, V., Bento, M., Burgess, J. A., Sanchez, J. C., Hochstrasser, D. F., Schrenzel, J., & Corthals, G. L. (2004). Nonredundant mass spectrometry: A strategy to integrate mass spectrometry acquisition and analysis. Proteomics, 4(4), 917–927. https://doi.org/10.1002/pmic.200300646
75. Street, J. M., & Dear, J. W. (2010). The application of mass-spectrometry-based protein biomarker discovery to theragnostics. British Journal of Clinical Pharmacology, 69(4), 367–378. https://doi.org/10.1111/j.1365-2125.2010.03612.x
76. Uyar, D. S., Huang, Y. W., Chesnik, M. A., Doan, N. B., & Mirza, S. P. (2021). Comprehensive serum proteomic analysis in early endometrial cancer. Journal of Proteomics, 234, Article 104099. https://doi.org/10.1016/j.jprot.2020.104099
77. Song, Y., Wang, M., Tong, H., Tan, Y., Hu, X., Wang, K., & Wan, X. (2021). Plasma exosomes from endometrial cancer patients contain LGALS3BP to promote endometrial cancer progression. Oncogene, 40(3), 633–646. https://doi.org/10.1038/s41388-020-01554-y
78. Lei, D., Hong, T., Li, L., Chen, L., Luo, X., Wu, Q., & Liu, Z. (2021). Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncology Letters, 21(2), Article 101. https://doi.org/10.3892/ol.2020.12362
79. Njoku, K., Sutton, C. J., Whetton, A. D., & Crosbie, E. J. (2020). Metabolomic biomarkers for detection, prognosis and identifying recurrence in endometrial cancer. Metabolites, 10(8), Article 314. https://doi.org/10.3390/metabo10080314
80. Njoku, K., Chiasserini, D., Jones, E. R., Barr, C. E., O’Flynn, H., Whetton, A. D., & Crosbie, E. J. (2020). Urinary biomarkers and their potential for the non-invasive detection of endometrial cancer. Frontiers in Oncology, 10, Article 559016. https://doi.org/10.3389/fonc.2020.559016
81. Liu, Z., Hong, Z., & Qu, P. (2020). Proteomic analysis of human endometrial tissues reveals the roles of PI3K/AKT/mTOR pathway and tumor angiogenesis molecules in the pathogenesis of endometrial cancer. Biomed Research International, 2020, Article 5273969. https://doi.org/10.1155/2020/5273969
82. Song, Y., Chen, Q. T., & He, Q. Q. (2019). Identification of key transcription factors in endometrial cancer by systems bioinformatics analysis. Journal of Cellular Biochemistry, 120(9), 15443–15454. https://doi.org/10.1002/jcb.28811
83. Kacirova, M., Bober, P., Alexovic, M., Tomkova, Z., Tkacikova, S., Talian, I., Mederova, L., Beresova, D., Toth, R., Andrasina, I., ... & Sabol, F. (2019). Differential urinary proteomic analysis of endometrial cancer. Physiological Research, 68(Suppl 4), S483–S490. https://doi.org/10.33549/physiolres.934372
84. Muinelo-Romay, L., Casas-Arozamena, C., & Abal, M. (2018). Liquid biopsy in endometrial cancer: New opportunities for personalized oncology. International Journal of Molecular Sciences, 19(8), Article 2311. https://doi.org/10.3390/ijms19082311
85. Ura, B., Monasta, L., Arrigoni, G., Franchin, C., Radillo, O., Peterlunger, I., Ricci, G., & Scrimin, F. (2017). A proteomic approach for the identification of biomarkers in endometrial cancer uterine aspirate. Oncotarget, 8(65), 109536–109545. https://doi.org/10.18632/oncotarget.22723
86. Alonso-Alconada, L., Santacana, M., Garcia-Sanz, P., Muinelo-Romay, L., Colas, E., Mirantes, C., Monge, M., Cueva, J., Oliva, E., Soslow, R. A., ... & Abal, M. (2015). Annexin-A2 as predictor biomarker of recurrent disease in endometrial cancer. International Journal of Cancer, 136(8), 1863–1873. https://doi.org/10.1002/ijc.29241
87. Tarney, C. M., Wang, G., Bateman, N. W., Conrads, K. A., Zhou, M., Hood, B. L., Loffredo, J., Tian, C., Darcy, K. M., Hamilton, C. A., ... & Maxwell, G. L. (2019). Biomarker panel for early detection of endometrial cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial. American Journal of Obstetrics and Gynecology, 221(5), 472.e1–472.e10. https://doi.org/10.1016/j.ajog.2019.05.045
88. Li, Z., Huang, C., Bai, S., Pan, X., Zhou, R., Wei, Y., & Zhao, X. (2008). Prognostic evaluation of epidermal fatty acid-binding protein and calcyphosine, two proteins implicated in endometrial cancer using a proteomic approach. International Journal of Cancer, 123(10), 2377–2383. https://doi.org/10.1002/ijc.23807
89. Wang, N., & Li, L. (2008). Exploring the precursor ion exclusion feature of liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry for improving protein identification in shotgun proteome analysis. Analytical Chemistry, 80(12), 4696–4710. https://doi.org/10.1021/ac800262x
90. Chen, H. S., Rejtar, T., Andreev, V., Moskovets, E., & Karger, B. L. (2005). Enhanced characterization of complex proteomic samples using LC-MALDI MS/MS: Exclusion of redundant peptides from MS/MS analysis in replicate runs. Analytical Chemistry, 77(23), 7816–7825. https://doi.org/10.1021/ac0511874
91. DeSouza, L. V., Grigull, J., Ghanny, S., Dube, V., Romaschin, A. D., Colgan, T. J., & Siu, K. W. (2007). Endometrial carcinoma biomarker discovery and verification using differentially tagged clinical samples with multidimensional liquid chromatography and tandem mass spectrometry. Molecular & Cellular Proteomics, 6(7), 1170–1182. https://doi.org/10.1074/mcp.M600465-MCP200
92. Byrjalsen, I., Mose Larsen, P., Fey, S. J., Nilas, L., Larsen, M. R., & Christiansen, C. (1999). Two-dimensional gel analysis of human endometrial proteins: Characterization of proteins with increased expression in hyperplasia and adenocarcinoma. Molecular Human Reproduction, 5(8), 748–756. https://doi.org/10.1093/molehr/5.8.748
93. Maxwell, G. L., Hood, B. L., Day, R., Chandran, U., Kirchner, D., Kolli, V. S., Bateman, N. W., Allard, J., Miller, C., Sun, M., ... & Conrads, T. P. (2011). Proteomic analysis of stage I endometrial cancer tissue: Identification of proteins associated with oxidative processes and inflammation. Gynecologic Oncology, 121(3), 586–594. https://doi.org/10.1016/j.ygyno.2011.01.033
94. Belkina, A. C., & Denis, G. V. (2012). BET domain co-regulators in obesity, inflammation and cancer. Nature Reviews Cancer, 12(7), 465–477. https://doi.org/10.1038/nrc3256
95. Bjune, J. I., Haugen, C., Gudbrandsen, O., Nordbø, O. P., Nielsen, H. J., Våge, V., Njølstad, P. R., Sagen, J. V., Dankel, S. N., & Mellgren, G. (2019). IRX5 regulates adipocyte amyloid precursor protein and mitochondrial respiration in obesity. International Journal of Obesity, 43(11), 2151–2162. https://doi.org/10.1038/s41366-019-0359-5
96. Cornelis, M. C., Rimm, E. B., Curhan, G. C., Kraft, P., Hunter, D. J., Hu, F. B., & van Dam, R. M. (2014). Obesity susceptibility loci and uncontrolled eating, emotional eating and cognitive restraint behaviors in men and women. Obesity, 22(5), E135–E141. https://doi.org/10.1002/oby.20696
97. Deng, Y., Wang, Z. V., Gordillo, R., Zhu, Y., Ali, A., Zhang, C., Wang, X., Shao, M., Zhang, Z., Iyengar, P., ... & Scherer, P. E. (2018). Adipocyte Xbp1s overexpression drives uridine production and reduces obesity. Molecular Metabolism, 11, 1–17. https://doi.org/10.1016/j.molmet.2018.02.013
98. Hooton, H., Dubern, B., Henegar, C., Paternoster, L., Nohr, E. A., Alili, R., Rousseau, F., Pelloux, V., Galan, P., Hercberg, S., ... & Clément, K. (2011). Association between CST3 rs2424577 polymorphism and corpulence related phenotypes during lifetime in populations of European ancestry. Obesity Facts, 4(2), 131–144. https://doi.org/10.1159/000327732
99. Steinberg, G. R. (2007). Inflammation in obesity is the common link between defects in fatty acid metabolism and insulin resistance. Cell Cycle, 6(8), 888–894. https://doi.org/10.4161/cc.6.8.4143
100. Zanardini, R., Benussi, L., Fostinelli, S., Saraceno, C., Ciani, M., Borroni, B., Padovani, A., Binetti, G., & Ghidoni, R. (2018). Serum C-Peptide, visfatin, resistin, and ghrelin are altered in sporadic and GRN-associated frontotemporal lobar degeneration. Journal of Alzheimer's Disease, 61(3), 1053–1060. https://doi.org/10.3233/JAD-170799
101. Urano, T., Shiraki, M., Sasaki, N., Ouchi, Y., & Inoue, S. (2015). SLC25A24 as a novel susceptibility gene for low fat mass in humans and mice. The Journal of Clinical Endocrinology & Metabolism, 100(4), E655–E663. https://doi.org/10.1210/jc.2014-3677
102. Yasin, H. K., Taylor, A. H., & Ayakannu, T. (2021). A narrative review of the role of diet and lifestyle factors in the development and prevention of endometrial cancer. Cancers, 13(9), Article 2149. https://doi.org/10.3390/cancers13092149
103. Boroń, D., Zmarzły, N., Wierzbik-Strońska, M., Rosińczuk, J., Mieszczański, P., & Grabarek, B. O. (2022). Recent multiomics approaches in endometrial cancer. International Journal of Molecular Sciences, 23(3), Article 1237. https://doi.org/10.3390/ijms23031237
104. Henry, J. L., Coggin, D. L., & King, C. R. (1993). High-level expression of the ribosomal protein L19 in human breast tumors that overexpress erbB-2. Cancer Research, 53(6), 1403–1408.
105. Barnard, G. F., Staniunas, R. J., Mori, M., Puder, M., Jessup, M. J., Steele, G. D., Jr., & Chen, L. B. (1993). Gastric and hepatocellular carcinomas do not overexpress the same ribosomal protein messenger RNAs as colonic carcinoma. Cancer Research, 53(17), 4048–4052.
106. Wang, H., Zhao, L. N., Li, K. Z., Ling, R., Li, X. J., & Wang, L. (2006). Overexpression of ribosomal protein L15 is associated with cell proliferation in gastric cancer. BMC Cancer, 6, Article 91. https://doi.org/10.1186/1471-2407-6-91
107. Kasai, H., Nadano, D., Hidaka, E., Higuchi, K., Kawakubo, M., & Sato, T. A. (2003). Differential expression of ribosomal proteins in human normal and neoplastic colorectum. Journal of Histochemistry & Cytochemistry, 51(5), 567–574. https://doi.org/10.1177/002215540305100502
108. El Khoury, W., & Nasr, Z. (2021). Deregulation of ribosomal proteins in human cancers. Bioscience Reports, 41(12), Article BSR20211577. https://doi.org/10.1042/BSR20211577
109. Vaarala, M. H., Porvari, K. S., Kyllonen, A. P., Mustonen, M. V., Lukkarinen, O., & Vihko, P. T. (1998). Several genes encoding ribosomal proteins are over-expressed in prostate-cancer cell lines: Confirmation of L7a and L37 over-expression in prostate-cancer tissue samples. International Journal of Cancer, 78(1), 27–32. https://doi.org/10.1002/(SICI)1097-0215(19981005)78:1<27::AID-IJC6>3.0.CO;2-I
110. Al-Juboori, A. A. A., Ghosh, A., Jamaluddin, M. F. B., Kumar, M., Sahoo, S. S., Syed, S. M., Nahar, P., & Tanwar, P. S. (2019). Proteomic analysis of stromal and epithelial cell communications in human endometrial cancer using a unique 3D co-culture model. Proteomics, 19(18), Article e1800448. https://doi.org/10.1002/pmic.201800448
111. Ayakannu, T., Taylor, A. H., & Konje, J. C. (2018). Cannabinoid receptor expression in estrogen-dependent and estrogen-independent endometrial cancer. Journal of Receptors and Signal Transduction, 38(5-6), 385–392. https://doi.org/10.1080/10799893.2018.1531885
112. Guida, M., Ligresti, A., De Filippis, D., D’Amico, A., Petrosino, S., Cipriano, M., Bifulco, G., Simonetti, S., Orlando, P., Insabato, L., ... & Di Marzo, V. (2010). The levels of the endocannabinoid receptor CB2 and its ligand 2-arachidonoylglycerol are elevated in endometrial carcinoma. Endocrinology, 151(3), 921–928. https://doi.org/10.1210/en.2009-0861
113. Ayakannu, T., Taylor, A. H., & Konje, J. C. (2021). Expression of the putative cannabinoid receptor GPR55 is increased in endometrial carcinoma. Histochemistry and Cell Biology, 156(5), 449–460. https://doi.org/10.1007/s00418-021-02021-8
114. Markowska, A., Pawałowska, M., Lubin, J., & Markowska, J. (2014). Signalling pathways in endometrial cancer. Contemporary Oncology, 18(3), 143–148. https://doi.org/10.5114/wo.2014.40504
115. Moukarzel, L. A., Ferrando, L., Stylianou, A., Lobaugh, S., Wu, M., Nobre, S. P., Iasonos, A., Zoppoli, G., Giri, D. D., Abu-Rustum, N. R., ... & Makker, V. (2022). Impact of obesity and white adipose tissue inflammation on the omental microenvironment in endometrial cancer. Cancer, 128(17), 3297–3309. https://doi.org/10.1002/cncr.34354
116. Yu, Z., Zhang, J., Zhang, Q., Wei, S., Shi, R., Zhao, R., An, L., Grose, R., Feng, D., & Wang, H. (2022). Single-cell sequencing reveals the heterogeneity and intratumoral crosstalk in human endometrial cancer. Cell Proliferation, 55(7), Article e13249. https://doi.org/10.1111/cpr.13249
117. Lu, K. H., & Broaddus, R. R. (2020). Endometrial cancer. New England Journal of Medicine, 383(21), 2053–2064. https://doi.org/10.1056/NEJMra1514010
118. Wu, C. H., & Chen, C. (2011). Bioinformatics for comparative proteomics. Humana Press. https://doi.org/10.1007/978-1-61779-182-6
119. Zervou, S., Yin, X., Nabeebaccus, A. A., O’Brien, B. A., Cross, R. L., McAndrew, D. J., Atkinson, R. A., Eykyn, T. R., Mayr, M., Neubauer, S., ... & Lygate, C. A. (2016). Proteomic and metabolomic changes driven by elevating myocardial creatine suggest novel metabolic feedback mechanisms. Amino Acids, 48(8), 1969–1981. https://doi.org/10.1007/s00726-016-2244-x