Sarkar Moumita, Sharma Harsh, Singh Parminder, Ranu Ranbala, Sharma Ravi Datta, Agrawal Usha, Pal Rahul
Immunoendocrinology Lab, National Institute of Immunology, New Delhi, Delhi 110067, India.
Amity Institute of Integrative Sciences and Health, Amity University, Gurugram, Haryana 122413, India.
iScience. 2022 Jun 3;25(7):104527. doi: 10.1016/j.isci.2022.104527. eCollection 2022 Jul 15.
The post-menopausal state in women is associated with increased cancer incidence, the reasons for which remain obscure. Curiously, increased circulating levels of beta-hCG (human chorionic gonadotropin) (a hormonal subunit linked with tumors of several lineages) are also often observed post-menopause. This study describes a previously unidentified interplay between beta-hCG and progesterone in tumorigenesis. Progesterone mediated apoptosis in beta-hCG responsive tumor cells via non-nuclear receptors. The transgenic expression of beta-hCG, particularly in the absence of the ovaries (a mimic of the post-menopausal state) constituted a potent pro-tumorigenic signal. Significantly, the administration of progesterone had significant anti-tumor effects. RNA-seq profiling identified molecular signatures associated with these processes. TCGA analysis revealed correlates between the expression of several newly identified genes and poor prognosis in post-menopausal patients of lung adenocarcinoma, colon adenocarcinoma, and glioblastoma. Specifically in these women, the detection of intra-tumoral/extra-tumoral beta-hCG may serve as a useful prognostic indicator, and treatment with progesterone on its detection may prove beneficial.
女性绝经后状态与癌症发病率增加有关，其原因尚不清楚。奇怪的是，绝经后也经常观察到循环中β-人绒毛膜促性腺激素（β-hCG，一种与多种谱系肿瘤相关的激素亚基）水平升高。本研究描述了β-hCG与孕酮在肿瘤发生过程中一种以前未被识别的相互作用。孕酮通过非核受体介导β-hCG反应性肿瘤细胞的凋亡。β-hCG的转基因表达，特别是在没有卵巢的情况下（模拟绝经后状态）构成了一种强大的促肿瘤信号。值得注意的是，给予孕酮具有显著的抗肿瘤作用。RNA测序分析确定了与这些过程相关的分子特征。TCGA分析揭示了几种新发现基因的表达与绝经后肺腺癌、结肠腺癌和胶质母细胞瘤患者预后不良之间的相关性。特别是在这些女性中，检测肿瘤内/肿瘤外β-hCG可能是一个有用的预后指标，检测到后用孕酮治疗可能证明是有益的。
