SCG2: A Prognostic Marker That Pinpoints Chemotherapy and Immunotherapy in Colorectal Cancer

BackgroundFluorouracil (FU)-based chemotherapy regimens are indispensable in the comprehensive treatment of colorectal cancer (CRC). However, the heterogeneity of treated individuals and the severe adverse effects of chemotherapy results in limited overall benefit.MethodsFirstly, Weighted gene co-ex...

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Main Authors: Siyuan Weng, Zaoqu Liu, Xiaofeng Ren, Hui Xu, Xiaoyong Ge, Yuqing Ren, Yuyuan Zhang, Qin Dang, Long Liu, Chunguang Guo, Richard Beatson, Jinhai Deng, Xinwei Han
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-07-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.873871/full
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author Siyuan Weng
Siyuan Weng
Siyuan Weng
Zaoqu Liu
Zaoqu Liu
Zaoqu Liu
Xiaofeng Ren
Hui Xu
Hui Xu
Hui Xu
Xiaoyong Ge
Xiaoyong Ge
Xiaoyong Ge
Yuqing Ren
Yuyuan Zhang
Qin Dang
Long Liu
Chunguang Guo
Richard Beatson
Jinhai Deng
Xinwei Han
Xinwei Han
Xinwei Han
author_facet Siyuan Weng
Siyuan Weng
Siyuan Weng
Zaoqu Liu
Zaoqu Liu
Zaoqu Liu
Xiaofeng Ren
Hui Xu
Hui Xu
Hui Xu
Xiaoyong Ge
Xiaoyong Ge
Xiaoyong Ge
Yuqing Ren
Yuyuan Zhang
Qin Dang
Long Liu
Chunguang Guo
Richard Beatson
Jinhai Deng
Xinwei Han
Xinwei Han
Xinwei Han
author_sort Siyuan Weng
collection DOAJ
description BackgroundFluorouracil (FU)-based chemotherapy regimens are indispensable in the comprehensive treatment of colorectal cancer (CRC). However, the heterogeneity of treated individuals and the severe adverse effects of chemotherapy results in limited overall benefit.MethodsFirstly, Weighted gene co-expression network analysis (WGCNA) identified modules tightly associated with chemotherapy response. Then, the in-house cohort and prognostic cohorts from TCGA and GEO were subjected to Cox proportional hazards model and survival analysis to ascertain the predictable function of SCG2 on the prognosis of CRC patients. Finally, we performed In vitro experiments, functional analysis, somatic mutation, and copy number variation research to explore the biological characteristics of SCG2.ResultsWe identified red and green as the modules most associated with chemotherapy response, in which SCG2 was considered a risky factor with higher expression predicting poorer prognosis. SCG2 expression in the APC non-mutation group was remarkably higher than in the mutation group. The mutation frequencies of amplified genes differed significantly between different SCG2 expression subgroups. Besides, CRC cell lines with SCG2 knockdown have reduced invasive, proliferative, and proliferative capacity. We discovered that the SCG2 high expression subgroup was the immune hot type and considered more suitable for immunotherapy.ConclusionThis study demonstrates the clinical significance and biological characteristics of SCG2, which could serve as a promising biomarker to identify patients who may benefit from chemotherapy and immunotherapy.
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spelling doaj.art-a1410210f94b4db1b2d816b70393aef92022-12-22T00:24:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.873871873871SCG2: A Prognostic Marker That Pinpoints Chemotherapy and Immunotherapy in Colorectal CancerSiyuan Weng0Siyuan Weng1Siyuan Weng2Zaoqu Liu3Zaoqu Liu4Zaoqu Liu5Xiaofeng Ren6Hui Xu7Hui Xu8Hui Xu9Xiaoyong Ge10Xiaoyong Ge11Xiaoyong Ge12Yuqing Ren13Yuyuan Zhang14Qin Dang15Long Liu16Chunguang Guo17Richard Beatson18Jinhai Deng19Xinwei Han20Xinwei Han21Xinwei Han22Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaInterventional Institute of Zhengzhou University, Zhengzhou, ChinaInterventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, ChinaDepartment of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaInterventional Institute of Zhengzhou University, Zhengzhou, ChinaInterventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, ChinaFaculty of Engineering and Information Technology University of Technology Sydney, Sydney, NSW, AustraliaDepartment of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaInterventional Institute of Zhengzhou University, Zhengzhou, ChinaInterventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, ChinaDepartment of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaInterventional Institute of Zhengzhou University, Zhengzhou, ChinaInterventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, ChinaDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaKing’s College London, School of Cancer and Pharmaceutical Sciences, Guy’s Cancer Centre, London, United Kingdom0Richard Dimbleby Laboratory of Cancer Research, School of Cancer and Pharmaceutical Sciences, King’s College London, London, United KingdomDepartment of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaInterventional Institute of Zhengzhou University, Zhengzhou, ChinaInterventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, ChinaBackgroundFluorouracil (FU)-based chemotherapy regimens are indispensable in the comprehensive treatment of colorectal cancer (CRC). However, the heterogeneity of treated individuals and the severe adverse effects of chemotherapy results in limited overall benefit.MethodsFirstly, Weighted gene co-expression network analysis (WGCNA) identified modules tightly associated with chemotherapy response. Then, the in-house cohort and prognostic cohorts from TCGA and GEO were subjected to Cox proportional hazards model and survival analysis to ascertain the predictable function of SCG2 on the prognosis of CRC patients. Finally, we performed In vitro experiments, functional analysis, somatic mutation, and copy number variation research to explore the biological characteristics of SCG2.ResultsWe identified red and green as the modules most associated with chemotherapy response, in which SCG2 was considered a risky factor with higher expression predicting poorer prognosis. SCG2 expression in the APC non-mutation group was remarkably higher than in the mutation group. The mutation frequencies of amplified genes differed significantly between different SCG2 expression subgroups. Besides, CRC cell lines with SCG2 knockdown have reduced invasive, proliferative, and proliferative capacity. We discovered that the SCG2 high expression subgroup was the immune hot type and considered more suitable for immunotherapy.ConclusionThis study demonstrates the clinical significance and biological characteristics of SCG2, which could serve as a promising biomarker to identify patients who may benefit from chemotherapy and immunotherapy.https://www.frontiersin.org/articles/10.3389/fimmu.2022.873871/fullcolorectal cancerchemotherapyprognosisimmunotherapybiomarker
spellingShingle Siyuan Weng
Siyuan Weng
Siyuan Weng
Zaoqu Liu
Zaoqu Liu
Zaoqu Liu
Xiaofeng Ren
Hui Xu
Hui Xu
Hui Xu
Xiaoyong Ge
Xiaoyong Ge
Xiaoyong Ge
Yuqing Ren
Yuyuan Zhang
Qin Dang
Long Liu
Chunguang Guo
Richard Beatson
Jinhai Deng
Xinwei Han
Xinwei Han
Xinwei Han
SCG2: A Prognostic Marker That Pinpoints Chemotherapy and Immunotherapy in Colorectal Cancer
Frontiers in Immunology
colorectal cancer
chemotherapy
prognosis
immunotherapy
biomarker
title SCG2: A Prognostic Marker That Pinpoints Chemotherapy and Immunotherapy in Colorectal Cancer
title_full SCG2: A Prognostic Marker That Pinpoints Chemotherapy and Immunotherapy in Colorectal Cancer
title_fullStr SCG2: A Prognostic Marker That Pinpoints Chemotherapy and Immunotherapy in Colorectal Cancer
title_full_unstemmed SCG2: A Prognostic Marker That Pinpoints Chemotherapy and Immunotherapy in Colorectal Cancer
title_short SCG2: A Prognostic Marker That Pinpoints Chemotherapy and Immunotherapy in Colorectal Cancer
title_sort scg2 a prognostic marker that pinpoints chemotherapy and immunotherapy in colorectal cancer
topic colorectal cancer
chemotherapy
prognosis
immunotherapy
biomarker
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.873871/full
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