Decreased secretoglobin family 2A member 1expression is associated with poor outcomes in endometrial cancer

Zhou,Hongyu; Zou,Xuan; Li,Haoran; Li,Tianjiao; Chen,Lihua; Cheng,Xi

doi:10.3892/ol.2020.11885

Decreased secretoglobin family 2A member 1expression is associated with poor outcomes in endometrial cancer

Authors:
- Hongyu Zhou
- Xuan Zou
- Haoran Li
- Tianjiao Li
- Lihua Chen
- Xi Cheng
View Affiliations

Affiliations: Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China
Published online on: July 16, 2020 https://doi.org/10.3892/ol.2020.11885
Article Number: 24
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Endometrial cancer is the most common malignancies in developed countries. The present study aimed to identify the role of secretoglobin family 2A member 1 (SCGB2A1) expression in uteri corpus endometrial carcinoma (UCEC) from The Cancer Genome Atlas (TCGA) database, and determine the SCGB2A1‑associated downstream signaling pathways. The clinicopathological characteristics and gene expression data were downloaded from TCGA database. The Kaplan‑Meier method and Cox multivariate model were used for survival analysis. Logistic regression was used to analyze the association between the clinicopathological features and SCGB2A1 expression. For validation, data of SCGB2A1 mRNA expression and protein expression were obtained and then survival analysis was performed for 47 patients with endometrial cancer from the Fudan University Shanghai Cancer Center (FUSCC). In TCGA dataset, SCGB2A1 expression was significantly higher in tumor tissues (n=528) compared with normal tissues (n=23, P<0.001). The decrease in SCGB2A1 expression in UCEC was significantly associated with age at diagnosis, high tumor grade, residual tumor, positive peritoneal cytology, pelvic lymph node metastasis, para‑aortic lymph node metastasis and advanced clinical stage with P<0.05. In the multivariate analysis, SCGB2A1 expression was identified as an independent prognostic factor. In the FUSCC validation set, low SCGB2A1 expression was also associated with worse survival compared with high expression in endometrial cancer (P<0.001). Gene Set Enrichment Analysis revealed that SCGB2A1 may be involved in tumor proliferation and cell cycle regulation. In conclusion, SCGB2A1 may have an important role in the prognosis of UCEC, and has value as a new target for novel therapeutic strategies.

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1	Urick ME and Bell DW: Clinical actionability of molecular targets in endometrial cancer. Nat Rev Cancer. 19:510–521. 2019. View Article : Google Scholar : PubMed/NCBI
2	Colombo N, Preti E, Landoni F, Carinelli S, Colombo A, Marini C and Sessa C; ESMO Guidelines Working Group, : Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 24 (Suppl 6):vi33–vi38. 2013. View Article : Google Scholar : PubMed/NCBI
3	Amant F, Mirza MR, Koskas M and Creutzberg CL: Cancer of the corpus uteri. Int J Gynaecol Obstet. 143 (Suppl 2):S37–S50. 2018. View Article : Google Scholar
4	Saso S, Chatterjee J, Georgiou E, Ditri AM, Smith JR and Ghaem-Maghami S: Endometrial cancer. BMJ. 343:d39542011. View Article : Google Scholar : PubMed/NCBI
5	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI
6	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
7	Tangjitgamol S, Anderson BO, See HT, Lertbutsayanukul C, Sirisabya N, Manchana T, Ilancheran A, Lee KM, Lim SE, Chia YN, et al: Management of endometrial cancer in Asia: Consensus statement from the Asian Oncology Summit 2009. Lancet Oncol. 10:1119–1127. 2009. View Article : Google Scholar : PubMed/NCBI
8	Morice P, Leary A, Creutzberg C, Abu-Rustum N and Darai E: Endometrial cancer. Lancet. 387:1094–1108. 2016. View Article : Google Scholar : PubMed/NCBI
9	Tanaka K, Kobayashi Y, Sugiyama J, Yamazaki T, Dozono K, Watanabe M, Shibuya H, Nishigaya Y, Momomura M, Matsumoto H, et al: Histologic grade and peritoneal cytology as prognostic factors in type 1 endometrial cancer. Int J Clin Oncol. 22:533–540. 2017. View Article : Google Scholar : PubMed/NCBI
10	Sorosky JI: Endometrial cancer. Obstet Gynecol. 120:383–397. 2012. View Article : Google Scholar : PubMed/NCBI
11	Odagiri T, Watari H, Kato T, Mitamura T, Hosaka M, Sudo S, Takeda M, Kobayashi N, Dong P, Todo Y, et al: Distribution of lymph node metastasis sites in endometrial cancer undergoing systematic pelvic and para-aortic lymphadenectomy: A proposal of optimal lymphadenectomy for future clinical trials. Ann Surg Oncol. 21:2755–2761. 2014. View Article : Google Scholar : PubMed/NCBI
12	Reijnen C, IntHout J, Massuger LFAG, Strobbe F, Küsters-Vandevelde HVN, Haldorsen IS, Snijders MPLM and Pijnenborg JMA: Diagnostic accuracy of clinical biomarkers for preoperative prediction of lymph node metastasis in endometrial carcinoma: A systematic review and meta-analysis. Oncologist. 24:e880–e890. 2019. View Article : Google Scholar : PubMed/NCBI
13	Arend RC, Jones BA, Martinez A and Goodfellow P: Endometrial cancer: Molecular markers and management of advanced stage disease. Gynecol Oncol. 150:569–580. 2018. View Article : Google Scholar : PubMed/NCBI
14	Le Gallo M and Bell DW: The emerging genomic landscape of endometrial cancer. Clin Chem. 60:98–110. 2014. View Article : Google Scholar : PubMed/NCBI
15	Murali R, Delair DF, Bean SM, Abu-Rustum NR and Soslow RA: Evolving roles of histologic evaluation and molecular/genomic profiling in the management of endometrial cancer. J Natl Compr Canc Netw. 16:201–209. 2018. View Article : Google Scholar : PubMed/NCBI
16	Becker RM, Darrow C, Zimonjic DB, Popescu NC, Watson MA and Fleming TP: Identification of mammaglobin B, a novel member of the uteroglobin gene family. Genomics. 54:70–78. 1998. View Article : Google Scholar : PubMed/NCBI
17	Xiao F, Mirwald A, Papaioannou M, Baniahmad A and Klug J: Secretoglobin 2A1 is under selective androgen control mediated by a peculiar binding site for Sp family transcription factors. Mol Endocrinol. 19:2964–2978. 2005. View Article : Google Scholar : PubMed/NCBI
18	Bellone S, Tassi R, Betti M, English D, Cocco E, Gasparrini S, Bortolomai I, Black JD, Todeschini P, Romani C, et al: Mammaglobin B (SCGB2A1) is a novel tumour antigen highly differentially expressed in all major histological types of ovarian cancer: Implications for ovarian cancer immunotherapy. Br J Cancer. 109:462–471. 2013. View Article : Google Scholar : PubMed/NCBI
19	Dieters-Castator DZ, Rambau PF, Kelemen LE, Siegers GM, Lajoie GA, Postovit LM and Köbel M: Proteomics-derived biomarker panel improves diagnostic precision to classify endometrioid and high-grade serous ovarian carcinoma. Clin Cancer Res. 25:4309–4319. 2019. View Article : Google Scholar : PubMed/NCBI
20	Tassi RA, Bignotti E, Rossi E, Falchetti M, Donzelli C, Calza S, Ravaggi A, Bandiera E, Pecorelli S and Santin AD: Overexpression of mammaglobin B in epithelial ovarian carcinomas. Gynecol Oncol. 105:578–585. 2007. View Article : Google Scholar : PubMed/NCBI
21	Tassi RA, Calza S, Ravaggi A, Bignotti E, Odicino FE, Tognon G, Donzelli C, Falchetti M, Rossi E, Todeschini P, et al: Mammaglobin B is an independent prognostic marker in epithelial ovarian cancer and its expression is associated with reduced risk of disease recurrence. BMC Cancer. 9:2532009. View Article : Google Scholar : PubMed/NCBI
22	Fischer K, von Brünneck AC, Hornung D, Denkert C, Ufer C, Schiebel H, Kuhn H and Borchert A: Differential expression of secretoglobins in normal ovary and in ovarian carcinoma-overexpression of mammaglobin-1 is linked to tumor progression. Arch Biochem Biophys. 547:27–36. 2014. View Article : Google Scholar : PubMed/NCBI
23	Tassi RA, Bignotti E, Falchetti M, Calza S, Ravaggi A, Rossi E, Martinelli F, Bandiera E, Pecorelli S and Santin AD: Mammaglobin B expression in human endometrial cancer. Int J Gynecol Cancer. 18:1090–1096. 2008. View Article : Google Scholar : PubMed/NCBI
24	McCluggage WG: Pathologic staging of endometrial carcinomas: Selected areas of difficulty. Adv Anat Pathol. 25:71–84. 2018. View Article : Google Scholar : PubMed/NCBI
25	Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES and Mesirov JP: Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 102:15545–15550. 2005. View Article : Google Scholar : PubMed/NCBI
26	Huang BL, Li X, Liu P, Ma L, Wu W, Zhang X, Li Z and Huang B: Transcriptomic analysis of Eruca vesicaria subs. sativa lines with contrasting tolerance to polyethylene glycol-simulated drought stress. BMC Plant Biol. 19:4192019. View Article : Google Scholar : PubMed/NCBI
27	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
28	Hua J, Shi S, Xu J, Wei M, Zhang Y, Liu J, Zhang B and Yu X: Expression patterns and prognostic value of DNA damage repair proteins in resected pancreatic neuroendocrine neoplasms. Ann Surg. Mar 20–2020.(Epub ahead of print). View Article : Google Scholar
29	Mercatali L, Valenti V, Calistri D, Calpona S, Rosti G, Folli S, Gaudio M, Frassineti GL, Amadori D and Flamini E: RT-PCR determination of maspin and mammaglobin B in peripheral blood of healthy donors and breast cancer patients. Ann Oncol. 17:424–428. 2006. View Article : Google Scholar : PubMed/NCBI
30	Aihara T, Fujiwara Y, Miyake Y, Okami J, Okada Y, Iwao K, Sugita Y, Tomita N, Sakon M, Shiozaki H and Monden M: Mammaglobin B gene as a novel marker for lymph node micrometastasis in patients with abdominal cancers. Cancer Lett. 150:79–84. 2000. View Article : Google Scholar : PubMed/NCBI
31	Bartosch C, Lopes JM and Jeronimo C: Epigenetics in endometrial carcinogenesis-part 1: DNA methylation. Epigenomics. 9:737–755. 2017. View Article : Google Scholar : PubMed/NCBI
32	Bignotti E, Tassi RA, Calza S, Ravaggi A, Rossi E, Donzelli C, Todeschini P, Romani C, Bandiera E, Zanotti L, et al: Secretoglobin expression in ovarian carcinoma: Lipophilin B gene upregulation as an independent marker of better prognosis. J Transl Med. 11:1622013. View Article : Google Scholar : PubMed/NCBI
33	Huang CY, Liao KW, Chou CH, Shrestha S, Yang CD, Chiew MY, Huang HT, Hong HC, Huang SH, Chang TH and Huang HD: Pilot study to establish a novel five-gene biomarker panel for predicting lymph node metastasis in patients with early stage endometrial cancer. Front Oncol. 9:15082019. View Article : Google Scholar : PubMed/NCBI