Abstract
BackgroundHigh-grade serous carcinoma (HGSC) of the ovary is the most common subtype of epithelial ovarian cancer (EOC) and has an overall poor prognosis. There is increasing awareness of the importance of immune cell populations and tumor-infiltrating lymphocytes (TILs) in various immune pathways in the tumor microenvironment. The present study evaluated immune-related gene expressions and TIL levels, as well as associated chemotherapeutic responses, to elucidate the correlation between gene expression and TIL levels in HGSC.Materials and methodsFresh tissue samples from 12 HGSC patients were included in this study. Depending on their response to adjuvant chemotherapy, the patients were divided into two groups: chemosensitive (CS) or chemoresistant (CR). The expression levels of 770 genes were analyzed using the nCounter® PanCancer Immune Profiling Panel of the NanoString nCounter® Analysis System. Quantitative real-time polymerase chain reaction (qPCR) was performed to validate the NanoString data obtained. The TIL levels in representative sections were examined via hematoxylin and eosin staining. Gene and TIL levels were subsequently correlated with the chemotherapeutic response.ResultsSeveral genes were differentially expressed in the two study groups. Eleven representative genes were selected for further evaluation. Of those, 9 genes (IRF1, CXCL9, LTB, CCL5, IL-8, GZMA, PSMB9, CD38, and VCAM1) were significantly overexpressed in the CS group; whereas expressions of 2 genes (CD24 and CD164) were increased in the CR group. Results of qPCR were consistent with those of the NanoString nCounter® analysis. Stromal TIL levels were significantly associated with adjuvant chemotherapeutic response (p = 0.001).ConclusionsSignificant differences between the CS and CR groups were observed in the expression levels of immune-related genes. Immune-related gene expressions were significantly higher in the CS group, which also had higher levels of TILs. We, therefore, suggest that, in patients with HGSC, immune-related gene expressions and TIL levels may be associated with chemotherapeutic sensitivity.
Highlights
Epithelial ovarian cancer (EOC) is a highly malignant neoplasm having a variable response to adjuvant chemotherapy
Stromal tumor-infiltrating lymphocytes (TILs) levels were significantly associated with adjuvant chemotherapeutic response (p = 0.001)
Suggest that, in patients with High-grade serous carcinoma (HGSC), immune-related gene expressions and TIL levels may be associated with chemotherapeutic sensitivity
Summary
Epithelial ovarian cancer (EOC) is a highly malignant neoplasm having a variable response to adjuvant chemotherapy. Even though patients may initially respond to treatment, the majority of HGSC patients subsequently develop platinum-resistance with relapse, thereby demonstrating an overall poor prognosis [3]. This unmet medical need has resulted in research to develop new potential therapeutic targets for patients with resistance to platinum chemotherapy and to assess the factors responsible for conferring the disparity between platinum-sensitivity and platinum-resistance. High-grade serous carcinoma (HGSC) of the ovary is the most common subtype of epithelial ovarian cancer (EOC) and has an overall poor prognosis. The present study evaluated immune-related gene expressions and TIL levels, as well as associated chemotherapeutic responses, to elucidate the correlation between gene expression and TIL levels in HGSC
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