The phosphatase PTPN1/PTP1B is a candidate marker of better chemotherapy response in metastatic high‐grade serous carcinoma

ObjectiveThe Chemotherapy Response Scoring (CRS) system was developed to enable reproducible reporting of histologic tumor response in interval debulking specimens following neoadjuvant chemotherapy in advanced stage tubo-ovarian high-grade serous carcinoma. This prognostic biomarker has been included in ovarian cancer pathology reporting guidelines (International Collaboration on Cancer Reporting, College of American Pathologists) and in the upcoming European Society for Medical Oncology-European Society of Gynaecological Oncology (ESMO-ESGO) guidelines for ovarian cancer management. We present follow-up data on the CRS validation initiatives and suggest research with novel therapeutic agents incorporating this biomarker.MethodsThe cohort on whom CRS was originally developed was analyzed after an extended follow-up of an additional 36 months. The CRS histopathologic scoring system was applied to omental sections obtained at interval surgery from all 80 patients. Progression-free and overall survival were re-calculated.ResultsAfter a median follow-up of 4.3 years the CRS score predicted progression-free survival with an HR of 0.39 (95% CI 0.21 to 0.70), p = 0.002 adjusted for age, stage, and debulking status (median 1.08 vs 2.27 years for CRS1/2 vs CRS3). CRS was also predictive of overall survival with an HR of 0.17 (95% CI 0.07 to 0.44), p = 0.0002 adjusted for age, stage, and debulking status (median 2.55 vs 5.47 years for CRS1/2 vs CRS3).ConclusionCRS3 is a reproducible prognostic biomarker for improved progression-free and overall survival in stage 3C or 4 tubo-ovarian high-grade serous carcinoma after neoadjuvant chemotherapy. The score, obtained at interval debulking surgery, can help facilitate research and biomarker driven first-line treatment of patients with advanced ovarian cancer.

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MicroRNA-625-3p improved proliferation and involved chemotherapy resistance via targeting PTEN in high grade ovarian serous carcinoma

Journal of Ovarian Research ◽

10.1186/s13048-021-00939-1 ◽

2022 ◽

Vol 15 (1) ◽

Author(s):

Lili Zhong ◽

Xiumin Liu ◽

Lixing Wang ◽

Yu Liu ◽

Duohan Zhang ◽

...

Keyword(s):

Clinical Stage ◽

Chemotherapy Resistance ◽

Luciferase Reporter ◽

Serous Carcinoma ◽

Migration And Invasion ◽

Chemotherapy Response ◽

High Grade ◽

Aberrant Expression ◽

Potential Biomarker ◽

Induced Apoptosis

Abstract Objective High-grade serous ovarian cancer (HGSOC) is an aggressive gynaecological malignancy and associated with poor prognosis. Here we examined the effects of miR-625-3p on proliferation, treatment, migration and invasion in HGSOC. Methods The proliferation of HGSOC cells was evaluated by MTT assay. Transwell assay was performed to examine migration and matrigel assay were used to assess invasion. The effect of miR-625-3p on cisplatin-induced apoptosis was investigated by Caspase-Glo3/7 assay. The dual-luciferase reporter assay was carried out to confirm the potential binding site. Results Overexpression of miR-625-3p promoted proliferation, and increased migration and invasion in HGSOC cells. MiR-625-3p significantly inhibited cisplatin sensitivity in HGSOC cells. Meanwhile, miR-625-3p decreased cisplatin-induced apoptosis by regulation of BAX and Bcl-2 expression. Furthermore, aberrant expression of miR-625-3p changed PTEN expression by directly binding to 3’UTR of PTEN. Further study showed miR-625-3p expression was higher in human HGSOC tissue than normal ovarian tissues and associated with higher clinical stage. Conclusions miR-625-3p promotes HGSOC growth, involves chemotherapy resistance and might serve as a potential biomarker to predict chemotherapy response and prognosis in HGSOC.

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