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Identification of a Six-Gene SLC Family Signature With Prognostic Value in Patients With Lung Adenocarcinoma

Given the importance of solute carrier (SLC) proteins in maintaining cellular metabolic homeostasis and that their dysregulation contributes to cancer progression, here we constructed a robust SLC family signature for lung adenocarcinoma (LUAD) patient stratification. Transcriptomic profiles and rel...

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Autores principales: Zhu, Jing, Mou, Yong, Ye, Shenglan, Hu, Hongling, Wang, Rujuan, Yang, Qing, Hu, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714960/
https://www.ncbi.nlm.nih.gov/pubmed/34977043
http://dx.doi.org/10.3389/fcell.2021.803198
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author Zhu, Jing
Mou, Yong
Ye, Shenglan
Hu, Hongling
Wang, Rujuan
Yang, Qing
Hu, Yi
author_facet Zhu, Jing
Mou, Yong
Ye, Shenglan
Hu, Hongling
Wang, Rujuan
Yang, Qing
Hu, Yi
author_sort Zhu, Jing
collection PubMed
description Given the importance of solute carrier (SLC) proteins in maintaining cellular metabolic homeostasis and that their dysregulation contributes to cancer progression, here we constructed a robust SLC family signature for lung adenocarcinoma (LUAD) patient stratification. Transcriptomic profiles and relevant clinical information of LUAD patients were downloaded from the TCGA and GEO databases. SLC family genes differentially expressed between LUAD tissues and adjacent normal tissues were identified using limma in R. Of these, prognosis-related SLC family genes were further screened out and used to construct a novel SLC family-based signature in the training cohort. The accuracy of the prognostic signature was assessed in the testing cohort, the entire cohort, and the external GSE72094 cohort. Correlations between the prognostic signature and the tumor immune microenvironment and immune cell infiltrates were further explored. We found that seventy percent of SLC family genes (279/397) were differentially expressed between LUAC tissues and adjacent normal. Twenty-six genes with p-values < 0.05 in univariate Cox regression analysis and Kaplan-Meier survival analysis were regarded as prognosis-related SLC family genes, six of which were used to construct a prognostic signature for patient classification into high- and low-risk groups. Kaplan-Meier survival analysis in all internal and external cohorts revealed a better overall survival for patients in the low-risk group than those in the high-risk group. Univariate and multivariate Cox regression analyses indicated that the derived risk score was an independent prognostic factor for LUAD patients. Moreover, a nomogram based on the six-gene signature and clinicopathological factors was developed for clinical application. High-risk patients had lower stromal, immune, and ESTIMATE scores and higher tumor purities than those in the low-risk group. The proportions of infiltrating naive CD4 T cells, activated memory CD4 T cells, M0 macrophages, resting dendritic cells, resting mast cells, activated mast cells, and eosinophils were significantly different between the high- and low-risk prognostic groups. In all, the six-gene SLC family signature is of satisfactory accuracy and generalizability for predicting overall survival in patients with LUAD. Furthermore, this prognostics signature is related to tumor immune status and distinct immune cell infiltrates in the tumor microenvironment.
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spelling pubmed-87149602021-12-30 Identification of a Six-Gene SLC Family Signature With Prognostic Value in Patients With Lung Adenocarcinoma Zhu, Jing Mou, Yong Ye, Shenglan Hu, Hongling Wang, Rujuan Yang, Qing Hu, Yi Front Cell Dev Biol Cell and Developmental Biology Given the importance of solute carrier (SLC) proteins in maintaining cellular metabolic homeostasis and that their dysregulation contributes to cancer progression, here we constructed a robust SLC family signature for lung adenocarcinoma (LUAD) patient stratification. Transcriptomic profiles and relevant clinical information of LUAD patients were downloaded from the TCGA and GEO databases. SLC family genes differentially expressed between LUAD tissues and adjacent normal tissues were identified using limma in R. Of these, prognosis-related SLC family genes were further screened out and used to construct a novel SLC family-based signature in the training cohort. The accuracy of the prognostic signature was assessed in the testing cohort, the entire cohort, and the external GSE72094 cohort. Correlations between the prognostic signature and the tumor immune microenvironment and immune cell infiltrates were further explored. We found that seventy percent of SLC family genes (279/397) were differentially expressed between LUAC tissues and adjacent normal. Twenty-six genes with p-values < 0.05 in univariate Cox regression analysis and Kaplan-Meier survival analysis were regarded as prognosis-related SLC family genes, six of which were used to construct a prognostic signature for patient classification into high- and low-risk groups. Kaplan-Meier survival analysis in all internal and external cohorts revealed a better overall survival for patients in the low-risk group than those in the high-risk group. Univariate and multivariate Cox regression analyses indicated that the derived risk score was an independent prognostic factor for LUAD patients. Moreover, a nomogram based on the six-gene signature and clinicopathological factors was developed for clinical application. High-risk patients had lower stromal, immune, and ESTIMATE scores and higher tumor purities than those in the low-risk group. The proportions of infiltrating naive CD4 T cells, activated memory CD4 T cells, M0 macrophages, resting dendritic cells, resting mast cells, activated mast cells, and eosinophils were significantly different between the high- and low-risk prognostic groups. In all, the six-gene SLC family signature is of satisfactory accuracy and generalizability for predicting overall survival in patients with LUAD. Furthermore, this prognostics signature is related to tumor immune status and distinct immune cell infiltrates in the tumor microenvironment. Frontiers Media S.A. 2021-12-15 /pmc/articles/PMC8714960/ /pubmed/34977043 http://dx.doi.org/10.3389/fcell.2021.803198 Text en Copyright © 2021 Zhu, Mou, Ye, Hu, Wang, Yang and Hu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Zhu, Jing
Mou, Yong
Ye, Shenglan
Hu, Hongling
Wang, Rujuan
Yang, Qing
Hu, Yi
Identification of a Six-Gene SLC Family Signature With Prognostic Value in Patients With Lung Adenocarcinoma
title Identification of a Six-Gene SLC Family Signature With Prognostic Value in Patients With Lung Adenocarcinoma
title_full Identification of a Six-Gene SLC Family Signature With Prognostic Value in Patients With Lung Adenocarcinoma
title_fullStr Identification of a Six-Gene SLC Family Signature With Prognostic Value in Patients With Lung Adenocarcinoma
title_full_unstemmed Identification of a Six-Gene SLC Family Signature With Prognostic Value in Patients With Lung Adenocarcinoma
title_short Identification of a Six-Gene SLC Family Signature With Prognostic Value in Patients With Lung Adenocarcinoma
title_sort identification of a six-gene slc family signature with prognostic value in patients with lung adenocarcinoma
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714960/
https://www.ncbi.nlm.nih.gov/pubmed/34977043
http://dx.doi.org/10.3389/fcell.2021.803198
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