Pyroptosis-related lncRNAs: A novel prognosis signature of colorectal cancer

Pyroptosis is a newly discovered programmed cell death mechanism involved in tumorigenesis. Long non-coding RNAs (lncRNAs) have been implicated in colorectal cancer (CRC). However, the potential role of pyroptosis-related lncRNAs (PRLs) in CRC remains unelucidated. Therefore, we retrieved transcript...

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Main Authors: Xing Cai, Xiaoqing Liang, Kun Wang, Yin Liu, Mengdi Hao, Huimin Li, Xiaofang Dai, Lei Ding
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.983895/full
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author Xing Cai
Xiaoqing Liang
Kun Wang
Yin Liu
Mengdi Hao
Huimin Li
Xiaofang Dai
Lei Ding
author_facet Xing Cai
Xiaoqing Liang
Kun Wang
Yin Liu
Mengdi Hao
Huimin Li
Xiaofang Dai
Lei Ding
author_sort Xing Cai
collection DOAJ
description Pyroptosis is a newly discovered programmed cell death mechanism involved in tumorigenesis. Long non-coding RNAs (lncRNAs) have been implicated in colorectal cancer (CRC). However, the potential role of pyroptosis-related lncRNAs (PRLs) in CRC remains unelucidated. Therefore, we retrieved transcriptomic data of CRC patients from The Cancer Genome Atlas (TCGA). With the use of univariate and multivariate Cox proportional hazards regression models and the random forest algorithm, a new risk model was constructed based on eight PRLs: Z99289.2, FENDRR, CCDC144NL-ASL, TEX41, MNX1-AS1, NKILA, LINC02798, and LINC02381. Then, according to the Kaplan–Meier plots, the relationship of PRLs with the survival of CRC patients was explored and validated with our risk model in external datasets (Gene Expression Omnibus (GEO) databases; GEO17536, n = 177, and GSE161158, n = 250). To improve its clinical utility, a nomogram combining PRLs that could predict the clinical outcome of CRC patients was established. A full-spectrum immune landscape of CRC patients mediated by PRLs could be described. The PRLs were stratified into two molecular subtypes involved in immune modulators, immune infiltration of tumor immune microenvironment, and inflammatory pathways. Afterward, Tumor Immune Dysfunction and Exclusion (TIDE) and microsatellite instability (MSI) scores were analyzed. Three independent methods were applied to predict PRL-related sensitivity to chemotherapeutic drugs. Our comprehensive analysis of PRLs in CRC patients demonstrates a potential role of PRLs in predicting response to treatment and prognosis of CRC patients, which may provide a better understanding of molecular mechanisms underlying CRC pathogenesis and facilitate the development of effective immunotherapy.
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spelling doaj.art-f5ddcd9023ca4f1e8a9e6ae6c455cced2022-12-22T04:36:48ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-11-011210.3389/fonc.2022.983895983895Pyroptosis-related lncRNAs: A novel prognosis signature of colorectal cancerXing Cai0Xiaoqing Liang1Kun Wang2Yin Liu3Mengdi Hao4Huimin Li5Xiaofang Dai6Lei Ding7Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaDepartment of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaDepartment of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaDepartment of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaDepartment of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaPyroptosis is a newly discovered programmed cell death mechanism involved in tumorigenesis. Long non-coding RNAs (lncRNAs) have been implicated in colorectal cancer (CRC). However, the potential role of pyroptosis-related lncRNAs (PRLs) in CRC remains unelucidated. Therefore, we retrieved transcriptomic data of CRC patients from The Cancer Genome Atlas (TCGA). With the use of univariate and multivariate Cox proportional hazards regression models and the random forest algorithm, a new risk model was constructed based on eight PRLs: Z99289.2, FENDRR, CCDC144NL-ASL, TEX41, MNX1-AS1, NKILA, LINC02798, and LINC02381. Then, according to the Kaplan–Meier plots, the relationship of PRLs with the survival of CRC patients was explored and validated with our risk model in external datasets (Gene Expression Omnibus (GEO) databases; GEO17536, n = 177, and GSE161158, n = 250). To improve its clinical utility, a nomogram combining PRLs that could predict the clinical outcome of CRC patients was established. A full-spectrum immune landscape of CRC patients mediated by PRLs could be described. The PRLs were stratified into two molecular subtypes involved in immune modulators, immune infiltration of tumor immune microenvironment, and inflammatory pathways. Afterward, Tumor Immune Dysfunction and Exclusion (TIDE) and microsatellite instability (MSI) scores were analyzed. Three independent methods were applied to predict PRL-related sensitivity to chemotherapeutic drugs. Our comprehensive analysis of PRLs in CRC patients demonstrates a potential role of PRLs in predicting response to treatment and prognosis of CRC patients, which may provide a better understanding of molecular mechanisms underlying CRC pathogenesis and facilitate the development of effective immunotherapy.https://www.frontiersin.org/articles/10.3389/fonc.2022.983895/fullpyroptosislong non coding RNAcolorectal cancerprognosisTCGA
spellingShingle Xing Cai
Xiaoqing Liang
Kun Wang
Yin Liu
Mengdi Hao
Huimin Li
Xiaofang Dai
Lei Ding
Pyroptosis-related lncRNAs: A novel prognosis signature of colorectal cancer
Frontiers in Oncology
pyroptosis
long non coding RNA
colorectal cancer
prognosis
TCGA
title Pyroptosis-related lncRNAs: A novel prognosis signature of colorectal cancer
title_full Pyroptosis-related lncRNAs: A novel prognosis signature of colorectal cancer
title_fullStr Pyroptosis-related lncRNAs: A novel prognosis signature of colorectal cancer
title_full_unstemmed Pyroptosis-related lncRNAs: A novel prognosis signature of colorectal cancer
title_short Pyroptosis-related lncRNAs: A novel prognosis signature of colorectal cancer
title_sort pyroptosis related lncrnas a novel prognosis signature of colorectal cancer
topic pyroptosis
long non coding RNA
colorectal cancer
prognosis
TCGA
url https://www.frontiersin.org/articles/10.3389/fonc.2022.983895/full
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