29 immune-related genes pairs signature predict the prognosis of cervical cancer patients

Abstract

To screen the key immune genes in the development of cervical cancer, construct immune related gene pairs (IRGPs), and evaluate their influence on the prognosis of cervical cancer. Tumor Genome Atlas (TCGA) database and geo database were downloaded as training set and validation set respectively, and immune related gene data were downloaded from immport. IRGPs model is established by machine learning, and the model is analyzed and evaluated. Using the Uclcan to analyze the immune genes expression in cervical cancer, and to further explore the association with the expression level and the clinical stage and prognosis of cervical cancer. According to the analysis of training set, we identified 29 IRGPs as key gene pairs and constructed the model. The AUC value of the model was greater than 0.9, and the model group survival rate was conspicuous different (P < 0.001). The reliability of the model was confirmed in the validation group. Our IRGPs play an important role in the occurrence and development of cervical cancer, and can be used as a prognostic marker and potential new target of cervical cancer. Cervical cancer is one of the four most common gynecological tumors 1. Every year, at least 569,847 women in the world are diagnosed with cervical cancer, and more than 311,365 people are killed 2. In recent years, the incidence rate of cervical cancer has decreased significantly through universal screening and health knowledge. However, the incidence rate of cervical cancer is still high in developing countries 3. For women with low education in less developed areas, the coverage rate of cervical cancer screening is still very low 4. Squamous cell carcinoma is the most common type of cervical cancer, accounting for 75% of cervical cancer cases, while adenocarcinoma only accounts for about 20%. In developing countries, 70% of cervical cancer patients have local infiltration or metastasis, which has led to the high mortality of cervical cancer in developing countries. Early cervical cancer is usually treated by radical hysterectomy. When there are risk factors such as lymph node metastasis and endometriosis that may lead to recurrence, they will be treated with chemotherapy 5. The standard treatment for patients with locally advanced cervical cancer is conventional radiation therapy(CRT) 6. The five-year survival rate of patients with locally advanced cervical cancer can be as high as 75-85% after surgical resection, radiotherapy, chemotherapy, CRT, and so on 7. However, at present, all treatment methods are not effective for patients with paraaortic lymph node metastasis, and their three-year progression free survival time (PFS) and total survival time (OS) are 34% and 39% 8,9 , respectively. The five-year survival rate of cervical cancer patients with recurrence and metastasis was as low as 15%. Limited treatment is the main reason for this situation. Now, palliative chemotherapy is the most commonly used for patients with metastatic and recurrent cervical cancer 10. The median survival time of patients with metastati...

Immune-Inhibitory Gene Expression is Positively Correlated with Overall Immune Activity and Predicts Increased Survival Probability of Cervical and Head and Neck Cancer Patients

“…Others have predicted the tumor-infiltrating immune cell composition in the TCGA CESC dataset using the metagene CIBERSORT approach, and found in line with our data that an enrichment of T cells was associated with increased survival probability (Wang et al, 2019). In addition to CD8 T cells, high infiltration of resting but not activated mast cells, stationary dendritic cells, and activated CD4 T cells in CESC were also found related to better survival (Yang et al, 2019;Nie et al, 2020). Resting mast cells and naïve B cells were recently selected as prognostic signatures (Che et al, 2020), where SCC patients were stratified into low and high risk groups.…”

“…Additionally, subjects with the lowest survival probability expressed very few immune-related genes at high levels, many of which are known to promote tumor progression, including IL1A, IL1B, and TGFB, and which were also correlated with increased FIGO stage. In a previous study, using immune related gene pairs (IRGPs), 29 IRGPs (47 genes) were proposed as prognostic immune markers to stratify CESC patients into low and high risk groups, and IL1B was also correlated with CESC development in the current study (Nie et al, 2020).…”

“…The heterogeneic nature of cancers including CESC thus requires methods for tumor stratification for prognostic purposes beyond the classical Tumor/Nodes/Metastasis (TNM) staging system, including the consensus Immunoscore (Pagès et al, 2018;Angell et al, 2020). Identification of prognostic immune-related gene signatures and the "Immunophenoscore" facilitated retrospective patient stratification in CESC (Charoentong et al, 2017;Thorsson et al, 2018;Yang et al, 2019;Nie et al, 2020;Qi et al, 2020) and will potentially guide immunotherapy selection to increase survival outcomes. However, identification of co-expressed immune networks will help to identify optimal targets for therapy.…”

Transcriptomic analysis and Novel gene pair-based signatures for Hepatitis B-related hepatocellular carcinoma

“…Only the pairs whose comparison was consistent in more than 80% of the samples could be included in the variable selection [15]. 10 folds Cross validation Lasso regression was implemented on the gene pairs by glmnet package in R. The gene pairs with coe cients not equal to zero continued to have a Best subset selection regression by bestglm package to further decrease the variates [16].…”

Discovery and Verification of an Immune-Related Gene Pairs Signature for Predicting Prognosis in Head and Neck Squamous Cell Carcinoma

“…Considering that the important roles of immune-related genes, there are emerging studies that calculate the score of immune-related gene pairs (IRGPs) based on its relative raking and report a significant correlation between IRGPs and the prognosis of cancer, including hepatocellular carcinoma, colorectal cancer, gastric cancer, lung adenocarcinoma and cervical cancer ( Wu et al, 2019 ; Zhang et al, 2019 ; Nie et al, 2020 ; Sun et al, 2020 ; Zhao et al, 2021 ). To our best knowledge, no study applying IRGPs to construct the prognostic signature in HNSCC.…”