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Selection of M7G-related lncRNAs in kidney renal clear cell carcinoma and their putative diagnostic and prognostic role

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is a common malignant tumor of the urinary system. This study aims to develop new biomarkers for KIRC and explore the impact of biomarkers on the immunotherapeutic efficacy for KIRC, providing a theoretical basis for the treatment of KIRC patients...

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Autores principales: Zhong, Shuangze, Chen, Shangjin, Lin, Hansheng, Luo, Yuancheng, He, Jingwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10652602/
https://www.ncbi.nlm.nih.gov/pubmed/37968670
http://dx.doi.org/10.1186/s12894-023-01357-9
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author Zhong, Shuangze
Chen, Shangjin
Lin, Hansheng
Luo, Yuancheng
He, Jingwei
author_facet Zhong, Shuangze
Chen, Shangjin
Lin, Hansheng
Luo, Yuancheng
He, Jingwei
author_sort Zhong, Shuangze
collection PubMed
description BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is a common malignant tumor of the urinary system. This study aims to develop new biomarkers for KIRC and explore the impact of biomarkers on the immunotherapeutic efficacy for KIRC, providing a theoretical basis for the treatment of KIRC patients. METHODS: Transcriptome data for KIRC was obtained from the The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Weighted gene co-expression network analysis identified KIRC-related modules of long noncoding RNAs (lncRNAs). Intersection analysis was performed differentially expressed lncRNAs between KIRC and normal control samples, and lncRNAs associated with N(7)-methylguanosine (m7G), resulting in differentially expressed m7G-associated lncRNAs in KIRC patients (DE-m7G-lncRNAs). Machine Learning was employed to select biomarkers for KIRC. The prognostic value of biomarkers and clinical features was evaluated using Kaplan-Meier (K-M) survival analysis, univariate and multivariate Cox regression analysis. A nomogram was constructed based on biomarkers and clinical features, and its efficacy was evaluated using calibration curves and decision curves. Functional enrichment analysis was performed to investigate the functional enrichment of biomarkers. Correlation analysis was conducted to explore the relationship between biomarkers and immune cell infiltration levels and common immune checkpoint in KIRC samples. RESULTS: By intersecting 575 KIRC-related module lncRNAs, 1773 differentially expressed lncRNAs, and 62 m7G-related lncRNAs, we identified 42 DE-m7G-lncRNAs. Using XGBoost and Boruta algorithms, 8 biomarkers for KIRC were selected. Kaplan-Meier survival analysis showed significant survival differences in KIRC patients with high and low expression of the PTCSC3 and RP11-321G12.1. Univariate and multivariate Cox regression analyses showed that AP000696.2, PTCSC3 and clinical characteristics were independent prognostic factors for patients with KIRC. A nomogram based on these prognostic factors accurately predicted the prognosis of KIRC patients. The biomarkers showed associations with clinical features of KIRC patients, mainly localized in the cytoplasm and related to cytokine-mediated immune response. Furthermore, immune feature analysis demonstrated a significant decrease in immune cell infiltration levels in KIRC samples compared to normal samples, with a negative correlation observed between the biomarkers and most differentially infiltrating immune cells and common immune checkpoints. CONCLUSION: In summary, this study discovered eight prognostic biomarkers associated with KIRC patients. These biomarkers showed significant correlations with clinical features, immune cell infiltration, and immune checkpoint expression in KIRC patients, laying a theoretical foundation for the diagnosis and treatment of KIRC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12894-023-01357-9.
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spelling pubmed-106526022023-11-15 Selection of M7G-related lncRNAs in kidney renal clear cell carcinoma and their putative diagnostic and prognostic role Zhong, Shuangze Chen, Shangjin Lin, Hansheng Luo, Yuancheng He, Jingwei BMC Urol Research BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is a common malignant tumor of the urinary system. This study aims to develop new biomarkers for KIRC and explore the impact of biomarkers on the immunotherapeutic efficacy for KIRC, providing a theoretical basis for the treatment of KIRC patients. METHODS: Transcriptome data for KIRC was obtained from the The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Weighted gene co-expression network analysis identified KIRC-related modules of long noncoding RNAs (lncRNAs). Intersection analysis was performed differentially expressed lncRNAs between KIRC and normal control samples, and lncRNAs associated with N(7)-methylguanosine (m7G), resulting in differentially expressed m7G-associated lncRNAs in KIRC patients (DE-m7G-lncRNAs). Machine Learning was employed to select biomarkers for KIRC. The prognostic value of biomarkers and clinical features was evaluated using Kaplan-Meier (K-M) survival analysis, univariate and multivariate Cox regression analysis. A nomogram was constructed based on biomarkers and clinical features, and its efficacy was evaluated using calibration curves and decision curves. Functional enrichment analysis was performed to investigate the functional enrichment of biomarkers. Correlation analysis was conducted to explore the relationship between biomarkers and immune cell infiltration levels and common immune checkpoint in KIRC samples. RESULTS: By intersecting 575 KIRC-related module lncRNAs, 1773 differentially expressed lncRNAs, and 62 m7G-related lncRNAs, we identified 42 DE-m7G-lncRNAs. Using XGBoost and Boruta algorithms, 8 biomarkers for KIRC were selected. Kaplan-Meier survival analysis showed significant survival differences in KIRC patients with high and low expression of the PTCSC3 and RP11-321G12.1. Univariate and multivariate Cox regression analyses showed that AP000696.2, PTCSC3 and clinical characteristics were independent prognostic factors for patients with KIRC. A nomogram based on these prognostic factors accurately predicted the prognosis of KIRC patients. The biomarkers showed associations with clinical features of KIRC patients, mainly localized in the cytoplasm and related to cytokine-mediated immune response. Furthermore, immune feature analysis demonstrated a significant decrease in immune cell infiltration levels in KIRC samples compared to normal samples, with a negative correlation observed between the biomarkers and most differentially infiltrating immune cells and common immune checkpoints. CONCLUSION: In summary, this study discovered eight prognostic biomarkers associated with KIRC patients. These biomarkers showed significant correlations with clinical features, immune cell infiltration, and immune checkpoint expression in KIRC patients, laying a theoretical foundation for the diagnosis and treatment of KIRC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12894-023-01357-9. BioMed Central 2023-11-15 /pmc/articles/PMC10652602/ /pubmed/37968670 http://dx.doi.org/10.1186/s12894-023-01357-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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
Zhong, Shuangze
Chen, Shangjin
Lin, Hansheng
Luo, Yuancheng
He, Jingwei
Selection of M7G-related lncRNAs in kidney renal clear cell carcinoma and their putative diagnostic and prognostic role
title Selection of M7G-related lncRNAs in kidney renal clear cell carcinoma and their putative diagnostic and prognostic role
title_full Selection of M7G-related lncRNAs in kidney renal clear cell carcinoma and their putative diagnostic and prognostic role
title_fullStr Selection of M7G-related lncRNAs in kidney renal clear cell carcinoma and their putative diagnostic and prognostic role
title_full_unstemmed Selection of M7G-related lncRNAs in kidney renal clear cell carcinoma and their putative diagnostic and prognostic role
title_short Selection of M7G-related lncRNAs in kidney renal clear cell carcinoma and their putative diagnostic and prognostic role
title_sort selection of m7g-related lncrnas in kidney renal clear cell carcinoma and their putative diagnostic and prognostic role
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10652602/
https://www.ncbi.nlm.nih.gov/pubmed/37968670
http://dx.doi.org/10.1186/s12894-023-01357-9
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