4.6 Article

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

Journal

FRONTIERS IN MEDICINE
Volume 8, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fmed.2021.755657

Keywords

tumor mutation burden; immune infiltration; prognosis; cervical squamous cell carcinoma; TCGA

Funding

  1. Pilot Gastric Cancer Project of Clinical Cooperation of Traditional Chinese and Western Medicine for Major and Difficult Diseases
  2. The Open Projects of the Discipline of Chinese Medicine of Nanjing University of Chinese Medicine by Subject of Academic Priority Discipline of Jiangsu Higher Education Institutions [ZYX03KF020]
  3. National Administration of Traditional Chinese Medicine [2019XZZX-ZL003]

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The study identified gene mutation characteristics in cervical squamous cell carcinoma and the association between tumor mutation burden (TMB) and prognosis. By establishing a prognostic model with five hub genes, the sensitivity of patients to immunotherapy can be predicted.
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.

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