Comprehensive analysis of lymph nodes metastasis associated genes in cervical cancer and its significance in treatment and prognosis

Abstract

Background Cervical carcinoma is one of the most common malignant tumors of the female reproductive system. Lymph nodes metastasis, the most common metastasis, which can be detected even in small-size tumor patients, results in worse prognosis. Therefore, it is of great significance to explore novel lymph nodes metastasis associated biomarkers, which can predict the prognosis and provide a good reference for clinical decision making in cervical carcinoma patients. However, systematic and comprehensive studies related to the key molecules in lymph node metastasis in cervical carcinoma patients are still absent. Methods Transcriptome and clinical data of 307 cervical carcinoma patients were obtained from The Cancer Genome Atlas (TCGA). Then, survival of patients with and without lymph node metastasis was analyzed by Kaplan-Meier (K-M) curves. Differential expressed genes (DEGs) were detected between tumor and control samples using limma package and defined as lymph node metastasis related genes. Univariate and multivariate Cox regression analyses were carried out to screen robust prognostic gene signature. The risk score model and nomogram for predicting survival were constructed based on prognostic gene signature. The performance of the risk score model was evaluated by operating characteristic (ROC) curves. Based on risk score, patients were divided into low- and high- risk groups. DEGs, functional enrichment analysis and tumor microenvironment (immune infiltration and expressions of immune checkpoints) were detected in low- and high-risk groups. Results A total of 103 lymph node metastasis-associated genes were identified. Univariate and multivariate Cox regression analyses identified TEKT2, LPIN2, FABP4 and CXCL2 as prognostic gene signature. The risk score model was constructed and validated in cervical carcinoma patients. 345 DEGs identified between high- and low-risk groups were significantly enriched into immune-related biological processes. Furthermore, we found that the immune infiltration and expressions of immune checkpoints were significantly different between low- and high-risk groups. Conclusion Our study revealed that lymph node metastasis played an important role in the prognosis of cervical carcinoma patients. Furthermore, we established a risk score model based on lymph node metastasis related genes, which could accurately predict the survival of cervical carcinoma patients. Besides, our findings in tumor microenvironments of low- and high-risk groups improved our understanding of the relationship between lymph node metastasis related genes and cervical carcinoma.

Identification of Immune and Hypoxia Risk Classifier to Estimate Immune Microenvironment and Prognosis in Cervical Cancer

“…Zhang et al once revealed that CXCL2 may promote tumor proliferation and metastasis induced by the overexpression of A-kinase-interacting protein 1 (AKIP1) in CC [ 40 ]. In agreement with our result, Yang et al recently indicated that the expression level CXCL2 is strongly associated with lymph node metastasis and prognosis in CC patients [ 41 ]. Four other genes including ITGA5, CCL20, TGFBI, and PLOD2 were previously studied in various malignancies, while their involvement in CC remains largely unexplored, and more basic researches are needed to reveal their biological function in CC [ 42 – 44 ].…”

Identification of Immune and Hypoxia Risk Classifier to Estimate Immune Microenvironment and Prognosis in Cervical Cancer

“…Zhang and his colleagues once revealed that CXCL2 may promote tumor proliferation and metastasis induced by the overexpression of A-kinaseinteracting protein 1 (AKIP1) in CC [36]. In agreement with our result, Yang et al recently indicated that the expression level CXCL2 is strongly associated with lymph node metastasis and prognosis in CC patients [37]. Four other genes including ITGA5, CCL20, TGFBI, and PLOD2 were previously studied in various malignancies, while their involvement in CC remains largely unexplored, and more basic researches are needed to reveal their biological function in CC [38][39][40].…”

Diagnostic, Prognostic, and Immunological Roles of FABP4 in Pancancer: A Bioinformatics Analysis

“…Meanwhile, disease-free survival (DFS) was found to be nificantly correlated with FABP4 expression in breast cancer (p = 0:049) [33]. Increased FABP4 expression is associated with worse OS and lymph node metastasis, which may be a potential and promising biomarker to assess lymph node status and survival, and may also be a new therapeutic target for patients with node-positive cervical cancer [34,35]. Similarly, high expression of FABP4 is considered to be associated with poor prognosis in breast, prostate, ovarian, and pancreatic cancers [36][37][38].…”