Chemotherapy-induced increase in CD47 expression in epithelial ovarian cancer.

Gland Surg

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Published: October 2024

AI Article Synopsis

  • Epithelial ovarian cancer (EOC) is the most deadly gynecological cancer with few treatment options, and CD47 is a key factor for tumors to evade the immune system, prompting research into CD47-targeted therapies alongside chemotherapy.
  • The study analyzed CD47 expression in 78 EOC patients' tissue samples, before and after neoadjuvant chemotherapy (NACT), finding that 80.8% of cases had CD47 expression and that its levels significantly increased post-chemotherapy.
  • Results showed that while CD47 expression varied among different ovarian cancer cell lines, it did not correlate with patient prognosis or clinicopathological characteristics, indicating a potential avenue for enhancing treatment

Article Abstract

Background: Epithelial ovarian cancer (EOC) remains the most lethal gynecological malignancy with limited treatment options. CD47 is a critical immune checkpoint for tumor immune evasion and has been targeted in various clinical trials. This study aimed to assess the impact of chemotherapy on CD47 expression in EOC in order to determine the potential and optimal timing of CD47-targeted therapy in ovarian cancer. We analyzed the expression of CD47 in ovarian cancer and the effect of chemotherapy on the expression of CD47 in ovarian cancer tissues. Furthermore, we investigated the effect of chemotherapy on the expression of CD47 in ovarian cancer cells.

Methods: CD47 expression was examined using immunohistochemistry (IHC) of specimens from 78 patients with EOC who underwent neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) with paired tissue specimens obtained before and after NACT. A retrospective review of the medical records was conducted to correlate demographic and survival data. Subsequently, we employed reverse transcription quantitative polymerase chain reaction (RT-qPCR) and flow cytometry analysis to examine and compare expression across human ovarian surface epithelial cell line (HOSE), SKOV3, and ES2 cells and to characterize the changes in CD47 expression in SKOV3 and ES2 cells after cisplatin treatment.

Results: CD47 expression was observed in 63 out of 78 (80.8%) cases before NACT. The expression of CD47 was not associated with the clinicopathological characteristics or the prognosis of patients with EOC. After three cancer specimens were excluded due to the absence of cancer cells following NACT, Wilcoxon exact tests of 75 pairs of matched specimens indicated that the expression of CD47 increased after chemotherapy (P=0.006). was expressed at varying levels in HOSE ovarian epithelial cells and SKOV3 and ES2 ovarian cancer cells. Notably, the messenger RNA (mRNA) expression of HOSE cells was observed to be lower than that of the SKOV3 and ES2 ovarian cancer cells (P<0.001). Following treatment with cisplatin, RT-qPCR indicated an increase in mRNA expression in SKOV3 and ES2 cells (P<0.001). Flow cytometry revealed a notable elevation in the cell surface CD47 protein mean fluorescence intensity of cisplatin-treated SKOV3 and ES2 cells (P<0.001).

Conclusions: CD47 is highly expressed in ovarian cancer, and NACT increases the expression of CD47, which may contribute to tumor immune evasion. It is possible that platinum-based chemotherapy may result in elevated mRNA expression and cell surface CD47 protein expression.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558286PMC
http://dx.doi.org/10.21037/gs-24-400DOI Listing

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