Identifying Potential Neoantigens for Cervical Cancer Immunotherapy Using Comprehensive Genomic Variation Profiling of Cervical Intraepithelial Neoplasia and Cervical Cancer

Frontiers in Oncology

Jun Luo¹  Ling Xu²  Wanqiu Huang³  Jian Huang³  Na An³  Chaohui Bao³  Hong Xie⁴  Boping Zhou⁴ 

[1] Department of Clinical Laboratory, Jiangsu Health Vocational College, Nanjing, China;Department of Obstetrics and Gynecology, Minhang Hospital, Fudan University, Shanghai, China;Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China;Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, Shenzhen, China;

关键词: cervical cancer;    cervical intraepithelial neoplasia;    genome variation;    neoantigens;    immunotherapy;   

DOI  :  10.3389/fonc.2021.672386

来源: DOAJ

【 摘 要 】

Cervical cancer (CC) is one of the most common gynecological malignant tumors. The 5-year survival rate remains poor for the advanced and metastatic cervical cancer for the lack of effective treatments. Immunotherapy plays an important role in clinical tumor therapy. Neoantigens derived from tumor-specific somatic mutations are prospective targets for immunotherapy. Hence, the identification of new targets is of great significance for the treatment of advanced and metastatic cervical cancer. In this study, we performed whole-exome sequencing in 70 samples, including 25 cervical intraepithelial neoplasia (CINs) with corresponding blood samples and 10 CCs along with paired adjacent tissues to identify genomic variations and to find the potential neoantigens for CC immunotherapy. Using systematic bioinformatics pipeline, we found that C>T transitions were in both CINs and CCs. In contrast, the number of somatic mutations in CCs was significantly higher than those in CINs (t-test, P = 6.60E-04). Meanwhile, mutational signatures analysis revealed that signature 6 was detected in CIN2, CIN3, and CC, but not in CIN1, while signature 2 was only observed in CCs. Furthermore, PIK3CA, ARHGAP5 and ADGRB1 were identified as potential driver genes in this report, of which ADGRB1 was firstly reported in CC. Based on the genomic variation profiling of CINs and CCs, we identified 2586 potential neoantigens in these patients, of which 45 neoantigens were found in three neoantigen-related databases (TSNAdb, IEDB, and CTDatabase). Our current findings lay a solid foundation for the study of the pathogenesis of CC and the development of neoantigen-targeted immunotherapeutic measures.

【 授权许可】

Unknown