Genomic profiles and their relationships with clinical characteristics and immune features in cervical cancer.

ABSTRACT

OBJECTIVE: This study aimed to investigate the genomic alteration profiles of cervical cancer patients, examine the correlation between mutation patterns and clinical and immune attributes, and discover novel targets for treatment of individuals with cervical cancer. METHODS: We performed targeted next-generation sequencing of tumor tissues and blood samples obtained from 45 cervical cancer patients to analyze somatic alterations, mutation patterns, and HLA alleles comprehensively. Additionally, we used flow cytometry to assess expression levels of immune checkpoint genes. RESULTS: Notably, genes such as AR (78%), KMT2D (76%), and NOTCH1 (62%) exhibited higher mutation frequencies. Moreover, the tumor mutation burden (TMB) was significantly greater in HPV-positive cervical cancer patients than in HPV-negative patients (P=0.029). BMI (P=0.047) and mutations in BARD1 (P=0.034), CEP290 (P=4E-04), and SLX4 (P=0.0128) were identified as predictors of shorter overall survival in cervical cancer patients. Furthermore, the present study revealed significant upregulation of PD-1 (P=0.027) and Tim-3 (P=0.048) in the high mutant-allele tumor heterogeneity (MATH) cohort. In the elderly cervical cancer patient population, HLA-A0301 emerged as a high-risk allele (OR=3.2, P<0.0001); HLA-C0702 (OR=0.073, P=0.02) and HLA-B*0702 (OR=0.257, P=0.037) were associated with a reduced risk among patients with low TMB. CONCLUSIONS: This study offers insights into the mutation characteristics of cervical cancer patients and identifies potential therapeutic.