التفاصيل البيبلوغرافية
| العنوان: |
Evaluation of ARID1A as a Potential Biomarker for Predicting Response to Immune Checkpoint Inhibitors in Patients with Endometrial Cancer. |
| المؤلفون: |
Yamashita, Hitomi, Nakayama, Kentaro, Kanno, Kosuke, Ishibashi, Tomoka, Ishikawa, Masako, Iida, Kouji, Razia, Sultana, Kiyono, Tohru, Kyo, Satoru |
| المصدر: |
Cancers; Jun2024, Vol. 16 Issue 11, p1999, 15p |
| مصطلحات موضوعية: |
PROTEIN analysis, PREDICTIVE tests, RESEARCH funding, TUMOR markers, DESCRIPTIVE statistics, ENDOMETRIAL tumors, IMMUNE checkpoint inhibitors, GENE expression, IMMUNOHISTOCHEMISTRY, COMPARATIVE studies, GENETIC mutation |
| مستخلص: |
Simple Summary: Endometrial cancer is the most common gynecological cancer. However, advanced and recurrent cancers are less sensitive to chemotherapy and have poor prognoses. Therefore, new treatment strategies are being explored. Recently, immune checkpoint inhibitors (ICIs) have been used in treating various cancers. Although AT-rich interaction domain 1A (ARID1A) negativity has been proposed as a new biomarker for immune checkpoint inhibitors, there have been no reports on ARID1A biomarkers in endometrial cancer. Therefore, we investigated whether ARID1A negativity predicts the efficacy of ICIs in treating endometrial cancer. We assessed ARID1A expression and tumor-infiltrating lymphocytes (CD8+) and immune checkpoint molecules (PD-L1/PD-1) using immunostaining and MSI analysis. Throughout our experiment, CD8 and PD-1 expression did not differ significantly between the ARID1A-negative and ARID1A-positive groups. Our findings suggest that ARID1A negativity may not be a suitable biomarker for ICI efficacy in endometrial cancer. Background: AT-rich interaction domain 1A (ARID1A) has been proposed as a new biomarker for predicting response to immune checkpoint inhibitors (ICIs). The predictive value of ARID1A for predicting ICI effectiveness has not been reported for endometrial cancer. Therefore, we investigated whether ARID1A negativity predicts ICI effectiveness for endometrial cancer treatment. Methods: We evaluated ARID1A expression, tumor-infiltrating lymphocytes (CD8+), and immune checkpoint molecules (PD-L1/PD-1) by immunostaining endometrial samples from patients with endometrial cancer. Samples in which any of the four mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) were determined to be negative via immunostaining were excluded. In the ARID1A-negative group, microsatellite instability (MSI) status was confirmed via MSI analysis. Results: Of the 102 samples investigated, 25 (24.5%) were ARID1A-negative. CD8 and PD-1 expression did not differ significantly between the ARID1A-negative group and the ARID1A-positive group; however, the ARID1A-negative group showed significantly lower PD-L1 expression. Only three samples (14.2%) in the ARID1A-negative group showed high MSI. Sanger sequencing detected three cases of pathological mutation in the MSH2-binding regions. We also established an ARID1A-knockout human ovarian endometriotic epithelial cell line (HMOsisEC7 ARID1A KO), which remained microsatellite-stable after passage. Conclusion: ARID1A negativity is not suitable as a biomarker for ICI effectiveness in treating endometrial cancer. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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