Upregulation of h-TERT and Ki-67 in ectopic endometrium is associated with recurrence of endometriosis

Alnafakh RAA, Adishesh M, Button L, et al., 2019. Telomerase and telomeres in endometrial cancer. Front Oncol, 9:344. https://doi.org/10.3389/fonc.2019.00344 Bozdag G, 2015. Recurrence of endometriosis: risk factors, mechanisms and biomarkers. Women’s Health, 11(5): 693–699. https://doi.org/10.2217/whe.15.56 Bubendorf L, Sauter G, Moch H, et al., 1996. Ki67 labelling index: an independent predictor of progression in prostate cancer treated by radical prostatectomy. J Pathol, 178(4): 437–441. https://doi.org/10.1002/(SICI)1096-9896(199604)178:43.0.CO;2-4 Ceccaroni M, Bounous VE, Clarizia R, et al., 2019. Recurrent endometriosis: a battle against an unknown enemy. Eur J Contracept Reprod Health Care, 24(6):464–474. https://doi.org/10.1080/13625187.2019.1662391 Chapron C, Marcellin L, Borghese B, et al., 2019. Rethinking mechanisms, diagnosis and management of endometriosis. Nat Rev Endocrinol, 15(11):666–682. https://doi.org/10.1038/s41574-019-0245-z Chiang HJ, Lin PY, Huang FJ, et al., 2015. The impact of previous ovarian surgery on ovarian reserve in patients with endometriosis. BMC Women’ s Health, 15:74. https://doi.org/10.1186/s12905-015-0230-1 de Ziegler D, Borghese B, Chapron C, 2010. Endometriosis and infertility: pathophysiology and management. Lancet, 376(9742):730–738. https://doi.org/10.1016/S0140-6736(10)60490-4 Ding L, Zhou YX, He C, et al., 2020. Elevated CA125 levels are associated with adverse clinical outcomes in acute pancreatitis: a propensity score-matched study. Pancreatology, 20(5):789–794. https://doi.org/10.1016/j-pan.2020.06.009 Greene AD, Lang SA, Kendziorski JA, et al., 2016. Endometriosis: where are we and where are we going? Reproduction, 152(3):R63–R78. https://doi.org/10.1530/REP-16-0052 Hanege BY, Çekiç SG, Ata B, 2019. Endometrioma and ovarian reserve: effects of endometriomata per se and its surgical treatment on the ovarian reserve. Facts Views Vis Obgyn, 11(2): 151–157. Hannen R, Bartsch JW, 2018. Essential roles of telomerase reverse transcriptase hTERT in cancer stemness and metastasis. FEBS Lett, 592(12):2023–2031. https://doi.org/10.1002/1873-3468.13084 Hu CJ, Ni ZH, Li BS, et al., 2017. hTERT promotes the invasion of gastric cancer cells by enhancing FOXO3a ubiquitination and subsequent ITGB1 upregulation. Gut, 66(1): 31–42. https://doi.org/10.1136/gutjnl-2015-309322 Kajiyama H, Suzuki S, Yoshihara M, et al., 2019. Endometriosis and cancer. Free Radic Biol Med, 133:186–192. https://doi.org/10.1016/j.freeradbiomed.2018.12.015 Kalaitzopoulos DR, Mitsopoulou A, Iliopoulou SM, et al., 2020. Association between endometriosis and gynecological cancers: a critical review of the literature. Arch Gynecol Obstet, 301(2):355–367. https://doi.org/10.1007/s00404-020-05445-1 Koga K, Takamura M, Fujii T, et al., 2015. Prevention of the recurrence of symptom and lesions after conservative surgery for endometriosis. Fertil Steril, 104(4):793–801. https://doi.org/10.1016/j.fertnstert.2015.08.026 Laganà AS, Garzon S, Götte M, et al., 2019. The pathogenesis of endometriosis: molecular and cell biology insights. Int J Mol Sci, 20(22):5615. https://doi.org/10.3390/ijms20225615 Li CH, Wang CH, 2021. LG-ESSs and HG-ESSs: underlying molecular alterations and potential therapeutic strategies. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 22(8): 633–646. https://doi.org/10.1631/jzus.B2000797 Li LT, Jiang G, Chen Q, et al., 2015. Ki67 is a promising molecular target in the diagnosis of cancer (review). Mol Med Rep, 11(3):1566–1572. https://doi.org/10.3892/mmr.2014.2914 Li XY, Chao XP, Leng JH, et al., 2019. Risk factors for postoperative recurrence of ovarian endometriosis: long-term follow-up of 358 women. J Ovarian Res, 12:79. https://doi.org/10.1186/s13048-019-0552-y Li Y, Li RQ, Ouyang NY, et al., 2019. Investigating the impact of local inflammation on granulosa cells and follicular development in women with ovarian endometriosis. Fertil Steril, 112(5):882–891.e1. https://doi.org/10.1016/j.fertnstert.2019.07.007 Liu SP, Xin WJ, Tang XY, et al., 2020. LncRNA H19 over-expression in endometriosis and its utility as a novel biomarker for predicting recurrence. Reprod Sci, 27(9): 1687–1697. https://doi.org/10.1007/s43032-019-00129-x McPeak AE, Allaire C, Williams C, et al., 2018. Pain catastrophizing and pain health-related quality-of-life in endometriosis. Clin J Pain, 34(4):349–356. https://doi.org/10.1097/AJP.0000000000000539 Miller I, Min MW, Yang C, et al., 2018. Ki67 is a graded rather than a binary marker of proliferation versus quiescence. Cell Rep, 24(5):1105–1112.e5. https://doi.org/10.1016/j.celrep.2018.06.110 Park JS, Lee JH, Kim M, et al., 2009. Endometrium from women with endometriosis shows increased proliferation activity. Fertil Steril, 92(4):1246–1249. https://doi.org/10.1016/j.fertnstert.2009.04.025 Poole JC, Andrews LG, Tollefsbol TO, 2001. Activity, function, and gene regulation of the catalytic subunit of telomerase (hTERT). Gene, 269(1–2):1–12. https://doi.org/10.1016/s0378-1119(01)00440-1 Rolla E, 2019. Endometriosis: advances and controversies in classification, pathogenesis, diagnosis, and treatment. F1000Research, 8:529. https://doi.org/10.12688/f1000research.14817.1 Sakamoto Y, Harada T, Horie S, et al., 2003. Tumor necrosis factor-α-induced interleukin-8 (IL-8) expression in endometriotic stromal cells, probably through nuclear factor-κB activation: gonadotropin-releasing hormone agonist treatment reduced IL-8 expression. J Clin Endocrinol Metab, 88(2):730–735. https://doi.org/10.1210/jc.2002-020666 Socolov R, Socolov D, Sindilar A, et al., 2017. An update on the biological markers of endometriosis. Minerva Ginecol, 69(5):462–467. https://doi.org/10.23736/S0026-4784.17.04046-1 Turk DC, 2002. Clinical effectiveness and cost-effectiveness of treatments for patients with chronic pain. Clin J Pain, 18(6):355–365. https://doi.org/10.1097/00002508-200211000-00003 Vercellini P, Viganò P, Somigliana E, et al., 2014. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol, 10(5): 261–275. https://doi.org/10.1038/nrendo.2013.255 Acknowledgments This work was supported by the Natural Science Foundation of Zhejiang Province (No. LGF20H040009), China. Author information Authors and Affiliations Contributions Jie LUO, Jun LIN, and Jianhong ZHOU conceived the study, participated in its design and coordination, and helped to draft the manuscript. Zhimin SONG carried out the immunohistochemistry studies and drafted the manuscript. Tao ZHANG and Ketan CHU were involved in clinical data collection and data analysis, and Jingyi LI was involved in revising the manuscript. All authors have read and approved the final manuscript, and therefore, take responsibility for the integrity of the study. Corresponding authors Ethics declarations Jie LUO, Zhimin SONG, Tao ZHANG, Ketan CHU, Jingyi LI, Jianhong ZHOU, and Jun LIN declared that they have no conflict of interests. The study was approved by the Human Ethics Committee of Women’s Hospital, Zhejiang University School of Medicine (No. 20190014), China. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5). Informed consent was obtained from all patients for being included in the study. 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Supplementary information Rights and permissions About this article Cite this article Luo, J., Song, Z., Zhang, T. et al. Upregulation of h-TERT and Ki-67 in ectopic endometrium is associated with recurrence of endometriosis. J. Zhejiang Univ. Sci. B 23, 158–163 (2022). https://doi.org/10.1631/jzus.B2100502 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1631/jzus.B2100502