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

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 nove...

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Autores principales: Yang, Ping, Ruan, Youqin, Yan, Zhiling, Gao, Yang, Yang, Hongying, Wang, Shaojia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597253/
https://www.ncbi.nlm.nih.gov/pubmed/34789197
http://dx.doi.org/10.1186/s12885-021-08945-8
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author Yang, Ping
Ruan, Youqin
Yan, Zhiling
Gao, Yang
Yang, Hongying
Wang, Shaojia
author_facet Yang, Ping
Ruan, Youqin
Yan, Zhiling
Gao, Yang
Yang, Hongying
Wang, Shaojia
author_sort Yang, Ping
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08945-8.
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spelling pubmed-85972532021-11-17 Comprehensive analysis of lymph nodes metastasis associated genes in cervical cancer and its significance in treatment and prognosis Yang, Ping Ruan, Youqin Yan, Zhiling Gao, Yang Yang, Hongying Wang, Shaojia BMC Cancer Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08945-8. BioMed Central 2021-11-16 /pmc/articles/PMC8597253/ /pubmed/34789197 http://dx.doi.org/10.1186/s12885-021-08945-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yang, Ping
Ruan, Youqin
Yan, Zhiling
Gao, Yang
Yang, Hongying
Wang, Shaojia
Comprehensive analysis of lymph nodes metastasis associated genes in cervical cancer and its significance in treatment and prognosis
title Comprehensive analysis of lymph nodes metastasis associated genes in cervical cancer and its significance in treatment and prognosis
title_full Comprehensive analysis of lymph nodes metastasis associated genes in cervical cancer and its significance in treatment and prognosis
title_fullStr Comprehensive analysis of lymph nodes metastasis associated genes in cervical cancer and its significance in treatment and prognosis
title_full_unstemmed Comprehensive analysis of lymph nodes metastasis associated genes in cervical cancer and its significance in treatment and prognosis
title_short Comprehensive analysis of lymph nodes metastasis associated genes in cervical cancer and its significance in treatment and prognosis
title_sort comprehensive analysis of lymph nodes metastasis associated genes in cervical cancer and its significance in treatment and prognosis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597253/
https://www.ncbi.nlm.nih.gov/pubmed/34789197
http://dx.doi.org/10.1186/s12885-021-08945-8
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