X-box Binding Protein 1 is a Potential Immunotherapy Target in Ovarian Cancer

Yanhui Jiang; Lewei Yang; Ling Jiang; Wenyan Yu; Zhongwen Jin; Yeqing Qiu; Yifeng Liao; Jihong Liu; Hongyu Zhang

doi:10.3389/fgene.2022.818917

X-box Binding Protein 1 is a Potential Immunotherapy Target in Ovarian Cancer

Front Genet. 2022 Aug 4:13:818917. doi: 10.3389/fgene.2022.818917. eCollection 2022.

Authors

Yanhui Jiang¹, Lewei Yang¹, Ling Jiang², Wenyan Yu¹, Zhongwen Jin¹, Yeqing Qiu¹, Yifeng Liao¹, Jihong Liu^{3

4}, Hongyu Zhang¹

Affiliations

¹ Cancer Center, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China.
² Department of Pathology, Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine, Zhuhai, China.
³ Department of Gynecology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China.
⁴ Department of Gynecologic Oncology, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Abstract

The allure of potentially dramatic and durable responses to immunotherapy has driven the study of several immune checkpoint inhibitor (ICI) agents in ovarian cancer. However, the results of ICI therapy in ovarian cancer have been rather disappointing. It is important to understand the reasons for the poor efficacy of ICI in ovarian cancer and to look for new targets for immunotherapy. To solve this problem, ovarian cancer-associated datasets were individually collected from The Cancer Genome Atlas (TCGA)、International Cancer Genome Consortium (ICGC)、Genotype-Tissue Expression (GTEx), and comprehensively performed to expression, prognostic, pathological correlation, genomic and immunologic analyses of reported all immune checkpoints by Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Tumor and Immune System Interaction Database (TISIDB), cBio Cancer Genomics Portal (cBioPortal), and Kaplan-Meier Plotter. We concluded that those well-identified immune checkpoints might not be ideal targets for ovarian cancer immunotherapy. Intriguingly, the genomic alteration of X-box binding protein 1 (XBP1), the important mediator of chemotherapy-induced cancer immunogenic cell death, was found to be a potential coregulator of immune checkpoints in ovarian cancer. Importantly, XBP1 was detected to be highly expressed in ovarian cancer compared with normal ovarian tissue, and high XBP1 expression significantly benefits both overall survival (OS) and disease-free survival (DFS) of ovarian cancer patients. More importantly, XBP1 was further observed to be closely related to anti-tumor immunity in ovarian cancer, including multiple T-cell signatures and immunity-killing molecules. In conclusion, upregulating XBP1 rather than targeting immune checkpoints represents a potentially more efficient approach for ovarian cancer therapy.

Keywords: XBP1; bioinformatics analysis; genomic alteration; immune checkpoint; immunogenic cell death; ovarian cancer.