Lumican is a potential predictor on the efficacy of concurrent chemoradiotherapy in cervical squamous cell carcinoma

Purpose: To identify new novel biomarkers for predicting the efficacy of concurrent chemoradiotherapy(CCRT) in cervical squamous cell carcinoma(CESC). Methods: Gene expression datasets GSE56363, GSE5787, and GSE168009 were analyzed to identify candidate genes to predict the efficacy of CCRT in CESC....

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Main Authors: Ge Hu, Ying Xiao, Chanchan Ma, Jinyun Wang, Xiaotao Qian, Xiaowei Wu, Fengqin Zhu, Shiying Sun, Junchao Qian
Format: Article
Language:English
Published: Elsevier 2023-07-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844023052192
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author Ge Hu
Ying Xiao
Chanchan Ma
Jinyun Wang
Xiaotao Qian
Xiaowei Wu
Fengqin Zhu
Shiying Sun
Junchao Qian
author_facet Ge Hu
Ying Xiao
Chanchan Ma
Jinyun Wang
Xiaotao Qian
Xiaowei Wu
Fengqin Zhu
Shiying Sun
Junchao Qian
author_sort Ge Hu
collection DOAJ
description Purpose: To identify new novel biomarkers for predicting the efficacy of concurrent chemoradiotherapy(CCRT) in cervical squamous cell carcinoma(CESC). Methods: Gene expression datasets GSE56363, GSE5787, and GSE168009 were analyzed to identify candidate genes to predict the efficacy of CCRT in CESC. Single-cell RNA sequencing (scRNA-seq) data from GSE168652 and CESC patients in The Cancer Genome Atlas(TCGA) were systematically analyzed to explore possible molecular mechanisms. Kaplan-Meier evaluated the correlation between LUM (Lumican) and prognostic significance. The expression of LUM protein in biopsy tissues before CCRT was detected by immunohistochemistry in 15 CESC patients. Results: LUM mRNA levels were significantly upregulated in nonresponders of CESC.patients receiving CCRT and positively correlated with poor therapeutic effect. Furthermore, high expression of LUM influenced the immune microenvironment in CESC patient-derived organoids treated with CCRT. LUM overexpression in CESC cells induced resistance to CCRT, potentially via immune landscape modulation. Gene Set Enrichment Analysis (GSEA) revealed that possible mechanisms underlying resistance to CCRT might involve the PARs and IL1 signaling pathway affecting the immune landscape. Conclusions: High LUM expression is correlated with poor efficacy in CESC patients receiving CCRT, possibly through the PARs and IL1 signaling pathway affecting the immune landscape.
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spelling doaj.art-1f2d115a1e214396820a0b5d0c143c412023-07-27T05:58:14ZengElsevierHeliyon2405-84402023-07-0197e18011Lumican is a potential predictor on the efficacy of concurrent chemoradiotherapy in cervical squamous cell carcinomaGe Hu0Ying Xiao1Chanchan Ma2Jinyun Wang3Xiaotao Qian4Xiaowei Wu5Fengqin Zhu6Shiying Sun7Junchao Qian8Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei,230031, PR ChinaThe Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 211100, PR ChinaDepartment of Obstetrics and Gynecology, Second Affiliated Hospital of Anhui Medical University, Hefei, 230031, PR ChinaHefei Cancer Hospital, Chinese Academy of Sciences, Hefei,230031, PR ChinaHefei Cancer Hospital, Chinese Academy of Sciences, Hefei,230031, PR ChinaHefei Cancer Hospital, Chinese Academy of Sciences, Hefei,230031, PR ChinaHefei Cancer Hospital, Chinese Academy of Sciences, Hefei,230031, PR ChinaDepartment of Obstetrics and Gynecology, Second Affiliated Hospital of Anhui Medical University, Hefei, 230031, PR China; Corresponding author.Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei,230031, PR China; Corresponding author.Purpose: To identify new novel biomarkers for predicting the efficacy of concurrent chemoradiotherapy(CCRT) in cervical squamous cell carcinoma(CESC). Methods: Gene expression datasets GSE56363, GSE5787, and GSE168009 were analyzed to identify candidate genes to predict the efficacy of CCRT in CESC. Single-cell RNA sequencing (scRNA-seq) data from GSE168652 and CESC patients in The Cancer Genome Atlas(TCGA) were systematically analyzed to explore possible molecular mechanisms. Kaplan-Meier evaluated the correlation between LUM (Lumican) and prognostic significance. The expression of LUM protein in biopsy tissues before CCRT was detected by immunohistochemistry in 15 CESC patients. Results: LUM mRNA levels were significantly upregulated in nonresponders of CESC.patients receiving CCRT and positively correlated with poor therapeutic effect. Furthermore, high expression of LUM influenced the immune microenvironment in CESC patient-derived organoids treated with CCRT. LUM overexpression in CESC cells induced resistance to CCRT, potentially via immune landscape modulation. Gene Set Enrichment Analysis (GSEA) revealed that possible mechanisms underlying resistance to CCRT might involve the PARs and IL1 signaling pathway affecting the immune landscape. Conclusions: High LUM expression is correlated with poor efficacy in CESC patients receiving CCRT, possibly through the PARs and IL1 signaling pathway affecting the immune landscape.http://www.sciencedirect.com/science/article/pii/S2405844023052192CESCLUMCCRTBiomarker
spellingShingle Ge Hu
Ying Xiao
Chanchan Ma
Jinyun Wang
Xiaotao Qian
Xiaowei Wu
Fengqin Zhu
Shiying Sun
Junchao Qian
Lumican is a potential predictor on the efficacy of concurrent chemoradiotherapy in cervical squamous cell carcinoma
Heliyon
CESC
LUM
CCRT
Biomarker
title Lumican is a potential predictor on the efficacy of concurrent chemoradiotherapy in cervical squamous cell carcinoma
title_full Lumican is a potential predictor on the efficacy of concurrent chemoradiotherapy in cervical squamous cell carcinoma
title_fullStr Lumican is a potential predictor on the efficacy of concurrent chemoradiotherapy in cervical squamous cell carcinoma
title_full_unstemmed Lumican is a potential predictor on the efficacy of concurrent chemoradiotherapy in cervical squamous cell carcinoma
title_short Lumican is a potential predictor on the efficacy of concurrent chemoradiotherapy in cervical squamous cell carcinoma
title_sort lumican is a potential predictor on the efficacy of concurrent chemoradiotherapy in cervical squamous cell carcinoma
topic CESC
LUM
CCRT
Biomarker
url http://www.sciencedirect.com/science/article/pii/S2405844023052192
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