Multi-Omics Data Analyses Construct a Six Immune-Related Genes Prognostic Model for Cervical Cancer in Tumor Microenvironment

Abstract

The cross-talk between tumor cells and the tumor microenvironment (TME) is an important factor in determining the tumorigenesis and progression of cervical cancer (CC). However, clarifying the potential mechanisms which trigger the above biological processes remains a challenge. The present study focused on immune-relevant differences at the transcriptome and somatic mutation levels through an integrative multi-omics analysis based on The Cancer Genome Atlas database. The objective of the study was to recognize the specific immune-related prognostic factors predicting the survival and response to immunotherapy of patients with CC. Firstly, eight hub immune-related prognostic genes were ultimately identified through construction of a protein–protein interaction network and Cox regression analysis. Secondly, 32 differentially mutated genes were simultaneously identified based on the different levels of immune infiltration. As a result, an immune gene-related prognostic model (IGRPM), including six factors (chemokine receptor 7 [CCR7], CD3d molecule [CD3D], CD3e molecule [CD3E], and integrin subunit beta 2 [ITGB2], family with sequence similarity 133 member A [FAM133A], and tumor protein p53 [TP53]), was finally constructed to forecast clinical outcomes of CC. Its predictive capability was further assessed and validated using the Gene Expression Omnibus validation set. In conclusion, IGRPM may be a promising prognostic signature to predict the prognoses and responses to immunotherapy of patients with CC. Moreover, the multi-omics study showed that IGRPM could be a novel therapeutic target for CC, which is a promising biomarker for indicating the immune-dominant status of the TME and revealing the potential mechanisms responsible for the tumorigenesis and progression of CC.

Identification of A Six Immune-Related Genes Prognostic Signature and Exploration of Individual Therapies in Young Women with Cervical Cancer

“…This unexpected result also suggested that low-risk patients possessed both immune activation and immunosuppression characteristics. This interesting phenomenon was previously reported by other authors 32,33 . We think this seemingly contradictory result also illustrates the complexity of tumor immunity in young CC patients, the potential mechanism is worth exploring further.…”

CD3D Is an Independent Prognostic Factor and Correlates With Immune Infiltration in Gastric Cancer

“…Some studies have shown that CD3D is involved in regulating the tumor immune microenvironment in cervical cancer, liver cancer, breast cancer and other tumors ( 12 – 14 ). Therefore, we further detected the expression of CD3, CD4, CD8 and PD-L1 in the tumor tissues of the included gastric cancer patients and evaluated their relationship with CD3D to explore the regulatory role of CD3D in the immune microenvironment of gastric cancer.…”

Recurrence- and Malignant Progression-Associated Biomarkers in Low-Grade Gliomas and Their Roles in Immunotherapy

“…FAM133A is a type of Cancer-Testis Antigen (CTA), a class of proteins that is highly expressed in immune privilege sites such as the brain and testis ( 57 ). High expression of FAM133A in cervical cancer and pancreatic cancer has been reported to be associated with the malignant degree of tumors ( 58 , 59 ). While in glioma, FAM133A is the downstream target of miR-155.…”