m6 A Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Infiltration Characterization in Early Cervical Cancer

Background Cervical cancer (CC) is the malignancy of female and almost cases of cervical cancer were caused by high-risk human papillomavirus (HPV) infection. Understanding the pathogenesis and characteristics of the postinfection microenvironment (PIM) in early-stage cervical cancer is needed. The mechanism of N6-methyladenosine (m6A) in the regulation of immune microenvironment in cervical cancer is unclear. Methods Messenger RNA (mRNA) expression profiles and clinical information of cervical cancer were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset GSE44001. We comprehensively evaluated the m6A modification patterns in early cervical cancer and systematically correlated these modification patterns with tumor microenvironment (TME) cell-infiltrating characteristics. Analysis of tumor mutational signatures and biological enrichment analysis were also conducted. Results LRPPRC had the highest mutation frequency. Writers METTL14 and ZC3H13, as well as reader YTHDF3, were prognostic risk-related genes. DEGs were significantly enriched in the C-type lectin receptor signaling pathway. The m6A cluster A showed a higher level of infiltration immunocytes, and the activity of most immune cells increased. The low-m6Sig score group was poor in prognosis compared with the high-m6Sig score group. Further, we found that the 23 immunocytes, excluding plasmacytoid dendritic cells, negatively correlated with the m6Sig score. Conclusions Dysregulation of m6A lays a critical foundation for understanding the regulation of early CC immunity. What’s more, evaluating the m6A modification pattern of early CC contributes to enhancing our knowledge of the characteristics of PIM and provides an important insight into the efficacy of HPV treatment.

Survival impact of additional chemotherapy after adjuvant concurrent chemoradiation in patients with early cervical cancer who underwent radical hysterectomy

Background To determine whether additional chemotherapy after concurrent chemoradiation (CCRT) improves survival outcomes in patients with early cervical cancer who undergo radical hysterectomy (RH). Methods We included high- or intermediate-risk patients from two institutions, with 2009 FIGO stage IB–IIA, who underwent primary RH and pelvic lymphadenectomy between January 2007 and June 2020, and had completed adjuvant CCRT. Survival outcomes were compared between patients who received additional chemotherapy (study group) and those who did not (control group). Results A total of 198 patients were included in this analysis. The study (n = 61) and control groups (n = 137) had similar patient age, histologic cancer type, 2009 FIGO stage, and tumor size. However, minimally invasive surgery was performed less frequently in the study group than in the control group (19.7% vs. 46.0%, P < 0.001). The presence of pathologic risk factors was similar, except for lymph node metastasis, which was more frequent in the study group (72.1% vs. 46.0%; P = 0.001). In survival analyses, no differences in the disease-free survival (DFS; P = 0.539) and overall survival (OS; P = 0.121) were observed between the groups. Multivariate analyses adjusting for surgical approach and other factors revealed that additional chemotherapy was not associated with DFS (adjusted HR, 1.149; 95% CI, 0.552–2.391; P = 0.710) and OS (adjusted HR, 1.877; 95% CI, 0.621–5.673; P = 0.264). The recurrence patterns did not differ with additional chemotherapy. Consistent results were observed in a subset of high-risk patients (n = 139). Conclusions Additional chemotherapy after CCRT might not improve survival outcomes in patients with early cervical cancer who undergo RH.