Prognostic Value of Tumor Mutational Burden Related to Immune Infiltration in Cervical Squamous Cell Carcinoma

Abstract

Cervical squamous cell carcinoma is one of the most common causes of female cancer deaths worldwide. At present, immunotherapy using immune checkpoint blockade (ICB) has improved the prognosis of many cancer patients, and neoantigens generated by mutations may serve as potential biomarkers for predicting the outcome of ICB therapy. In this study, we identified missense mutations as the most frequent in landscapes of gene mutation in cervical squamous cell carcinoma (CESC) samples. Patients with higher tumor mutation burden (TMB) presented higher overall survival (OS). In addition, there was a significant correlation between the high TMB group and fractions of most immune cells. Univariate and multivariate Cox regression analyses identified five hub genes (IFNG, SERPINA3, CCL4L2, TNFSF15, and IL1R1) that were used to build a prognostic model. In the prognostic model, the low-risk group achieved better OS. Mutations in the five hub genes mainly affected the infiltration level of CD8+ T cells and dendritic cells. In conclusion, our study is valuable for exploring the role of TMB and its relationship with immune infiltration in CESC. Moreover, the prognosis model may help predict the sensitivity of patients to immunotherapy and provide underlying biomarkers for personalized immunotherapy.

Construction and comprehensive analysis of a curoptosis-related lncRNA signature for predicting prognosis and immune response in cervical cancer

“…Clinically, sequencing Frontiers in Genetics frontiersin.org of patients receiving immunotherapy by grouping them according to this risk score can predict the effect of immunotherapy. Mutations in cancer-causing genes are significantly associated with cancer, and CESC patients with high TMB have better survival outcomes (Wen et al, 2021), consistent with our results. Combined analysis of high-and low-risk scores and TMB in the HRG and LRG showed that patients with high TMB combined with low-risk scores had a significantly higher survival rate.…”

Increased human papillomavirus viral load is correlated to higher severity of cervical disease and poorer clinical outcome: A systematic review

“…168 Last, as a further potentially useful DNA-level measurement, tumor mutational burden (TMB) has been studied in cervical cancer. It is currently unclear which particular genes contribute most to the TMB, 169,170 as the integration site of HPV within the host genome is not universally conserved. 171 There is evidence that high TMB cervical cancer patients exhibit more severe disease, along with increased stage and lymph nodes.…”

“…173 The same has been confirmed by other groups, who found that TMB indeed not only holds prognostic value, but is also related to the infiltration level of immune cells within the tumor microenvironment, which directly links to the success of checkpoint inhibitors. 170 Furthermore, HPV-positive cervical cancers have been shown to have higher TMB, 174 leaving the question as to whether this may be linked to viral load open to further research.…”