WITHDRAWN: Multimodal genetic features correlate with poor response to neoadjuvant chemoradiotherapy and high recurrence risk in Chinese patients with stage IB-IIA cervical cancer

Abstract

Background Response of cervical cancer patients to neoadjuvant therapy differs from person to person. It remains unclear whether genetic alterations can predict response to neoadjuvant therapy and disease-free survival in cervical cancer.Methods 62 Chinese patients with stage IB-IIA cervical cancer were included in this study. Pre-treatment tumor tissues were profiled using a targeted next-generation sequencing assay. Genetic alterations were compared with those identified in the Western populations using the TCGA database. Pathological response and disease-free survival (DFS) were evaluated and their correlations with genetic alterations were analyzed.Results Genetic alterations in PIK3CA were prevalent in both Chinese and Caucasian populations. The mutation frequencies of TERT, POLD1, NOS2, and FGFR3 were significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were frequently mutated in Caucasian patients. Germline mutations were identified in 13 out of 62 Chinese patients and 57% of them occurred in DNA repair genes, such as BRCA1/2, TP53 and PALB2. High tumor mutation burden (TMB), TP53 polymorphism (rs1042522) and KEAP1 mutations were found to be associated with poor response to neoadjuvant therapy. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC amplification and TYMS polymorphism were associated with higher relapse rates of cervical cancer.Conclusion The similarity and difference of mutation landscape of Chinese and Caucasian patients suggested genetic background played a role in shaping the architecture of cervical cancer mutations. The associations of mutation feature of cervical cancer with patient response and tumor recurrence risk provided rationale to further validate and explore potential biomarkers for cervical cancer patients.