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pmid:35250999

Construction of a Lactate-Related Prognostic Signature for Predicting Prognosis, Tumor Microenvironment, and Immune Response in Kidney Renal Clear Cell Carcinoma.

Zhuolun Sun · Wen Tao · Xudong Guo · Changying Jing · Mingxiao Zhang · Zhenqing Wang · Feng Kong · Ning Suo · Shaobo Jiang · Hanbo Wang

Frontiers in immunology · 2022 doi:10.3389/fimmu.2022.818984

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complete

Experiment

complete

Data

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Analysis

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Execution

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title
Construction of a Lactate-Related Prognostic Signature for Predicting Prognosis, Tumor Microenvironment, and Immune Response in Kidney Renal Clear Cell Carcinoma.
doi
10.3389/fimmu.2022.818984
pmid
35250999
authors array · 10 items
[0]
Zhuolun Sun
[1]
Wen Tao
[2]
Xudong Guo
[3]
Changying Jing
[4]
Mingxiao Zhang
[5]
Zhenqing Wang
[6]
Feng Kong
[7]
Ning Suo
[8]
Shaobo Jiang
[9]
Hanbo Wang
journal
Frontiers in immunology
year
2022
abstract
Kidney renal clear cell carcinoma (KIRC) is one of the most prevalent primary malignancies with high heterogeneity in the urological system. Growing evidence implies that lactate is a significant carbon source for cell metabolism and plays a vital role in tumor development, maintenance, and therapeutic response. However, the global influence of lactate-related genes (LRGs) on prognostic significance, tumor microenvironment characteristics, and therapeutic response has not been comprehensively elucidated in patients with KIRC. In the present study, we collected RNA sequencing and clinical data of KIRC from The Cancer Genome Atlas (TCGA), E-MTAB-1980, and GSE22541 cohorts. Unsupervised clustering of 17 differentially expressed LRG profiles divided the samples into three clusters with distinct immune characteristics. Three genes (FBP1, HADH, and TYMP) were then identified to construct a lactate-related prognostic signature (LRPS) using the least absolute shrinkage and selection operator (LASSO) and Cox regression analyses. The novel signature exhibited excellent robustness and predictive ability for the overall survival of patients. In addition, the constructed nomogram based on the LRPS-based risk scores and clinical factors (age, gender, tumor grade, and stage) showed a robust predictive performance. Furthermore, patients classified by risk scores had distinguishable immune status, tumor mutation burden, response to immunotherapy, and sensitivity to drugs. In conclusion, we developed an LRPS for KIRC that was closely related to the immune landscape and therapeutic response. This LRPS may guide clinicians to make more precise and personalized treatment decisions for KIRC patients.
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Differential expression of the LRGs was analyzed between the normal and tumor groups using the “limma” package in R, with p < 0.05 and |log2 fold change (FC)| ≥ 1.50.
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Differential expression of the LRGs was analyzed between the normal and tumor groups using the “limma” package in R, with p < 0.05 and |log2 fold change (FC)| ≥ 1.50.
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Publicly available datasets were analyzed in this study. This data can be found here: https://portal.gdc.cancer.gov/, https://www.ncbi.nlm.nih.gov/, and https://www.ebi.ac.uk/.
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In conclusion, we developed an LRPS for KIRC that was closely related to the immune landscape and therapeutic response.
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Growing evidence implies that lactate is a significant carbon source for cell metabolism and plays a vital role in tumor development, maintenance, and therapeutic response. However, the global influence of lactate-related genes (LRGs) on prognostic significance, tumor microenvironment characteristics, and therapeutic response has not been comprehensively elucidated in patients with KIRC. In the present study, we collected RNA sequencing and clinical data of KIRC from The Cancer Genome Atlas (TCGA), E-MTAB-1980, and GSE22541 cohorts. Unsupervised clustering of 17 differentially expressed LRG profiles divided the samples into three clusters with distinct immune characteristics. Three genes (FBP1, HADH, and TYMP) were then identified to construct a lactate-related prognostic signature (LRPS) using the least absolute shrinkage and selection operator (LASSO) and Cox regression analyses. The novel signature exhibited excellent robustness and predictive ability for the overall survival of patients. In addition, the constructed nomogram based on the LRPS-based risk scores and clinical factors (age, gender, tumor grade, and stage) showed a robust predictive performance. Furthermore, patients classified by risk scores had distinguishable immune status, tumor mutation burden, response to immunotherapy, and sensitivity to drugs. In conclusion, we developed an LRPS for KIRC that was closely related to the immune landscape and therapeutic response. 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