Masuma Khatun

Stanniocalcin Protein Expression in Female Reproductive Organs: Literature Review and Public Cancer Database Analysis

Abstract Stanniocalcin (STC) 1 and 2 serve as antihyperglycemic polypeptide hormones with critical roles in regulating calcium and phosphate homeostasis. They additionally function as paracrine and/or autocrine factors involved in numerous physiological processes, including female reproduction. STC1 and STC2 contribute to the pathophysiology of several diseases, including female infertility- and pregnancy-associated conditions, and even tumorigenesis of reproductive organs. This comprehensive review highlights the dynamic expression patterns and potential dysregulation of STC1 and STC2, restricted to female fertility, and infertility- and pregnancy-associated diseases and conditions, such as endometriosis, polycystic ovary syndrome (PCOS), abnormal uterine bleeding, uterine polyps, and pregnancy complications, like impaired decidualization, preeclampsia, and preterm labor. Furthermore, the review elucidates the role of dysregulated STC in the progression of cancers of the reproductive system, including endometrial, cervical, and ovarian cancers. Additionally, the review evaluates the expression patterns and prognostic significance of STC in gynecological cancers by utilizing existing public datasets from The Cancer Genome Atlas to help decipher the multifaceted roles of these pleiotropic hormones in disease progression. Understanding the intricate mechanisms by which STC proteins influence all these reviewed conditions could lead to the development of targeted diagnostic and therapeutic strategies in the context of female reproductive health and oncology.

PPP2R1A mutation status as a predictive and prognostic factor in molecularly characterized endometrial carcinoma: a cohort study

To evaluate associations of mutations in PPP2R1A, encoding the Aα subunit of protein phosphatase 2A (PP2A), with molecular sub-groups, clinicopathologic factors, predictive/prognostic biomarkers, and survival in endometrial carcinoma. This retrospective study used sequencing, immunohistochemistry, and dual-color chromogenic in situ hybridization to assess PPP2R1A mutations, molecular sub-groups, and PD-L1, human epidermal growth factor receptor 2 (HER2), estrogen receptor, and L1 cell adhesion molecule status. A total of 436 patients were analyzed (median follow-up: 48 months). A total of 37 tumors (8.4%) harbored PPP2R1A mutations. They were associated with stage II to IV disease (p = .010), molecular sub-group (p < .001), and histotype (p < .001). Among PPP2R1A-mutated tumors, 54.1% (n = 20) were p53-abnormal, and 40.5% (n = 15) were non-endometrioid. Mismatch repair, PD-L1, HER2, and L1 cell adhesion molecule status did not differ between the PPP2R1A-mutated and wild-type groups. Estrogen receptor expression was more common in wild-type tumors (p = .003). Of the 33 PPP2R1A-mutated tumors with known mismatch repair and PD-L1 immunohistochemistry and HER2 amplification status, 51.5% (n = 17) were negative for all signatures. When estrogen receptor was included as a predictive parameter, 13.3% (4 of 30) were negative for all 4. PPP2R1A mutations were associated with poorer progression-free (p = .001) and disease-specific survival (p < .001) but not overall survival (p = .058). After adjusting for molecular sub-groups and clinicopathological risk groups, PPP2R1A mutations were not associated with outcomes. Among PPP2R1A-mutated tumors, p53 abnormalities were associated with poorer outcomes than the p53 wild-type phenotype. Although PPP2R1A mutations are linked to aggressive clinicopathological features, they do not independently predict endometrial carcinoma survival. Given the absence of non-hormonal targets in half of PPP2R1A-mutated carcinomas, PP2A-targeted therapies are needed. Survival analysis suggests that the role of p53 in progression likely extends beyond its interaction with PP2A.