Integrated Profiling Identifies PLOD3 as a Potential Prognostic and Immunotherapy Relevant Biomarker in Colorectal Cancer

Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 3 (PLOD3) is related to a variety of human diseases. However, its function in Colorectal cancer (CRC) remains uncertain. PLOD3 expression was analyzed using The Cancer Genome Atlas (TCGA) pan-cancer data. DAVID was used for enrichment analysis of PLOD3...

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Main Authors: Junhong Shi, Meiyu Bao, Weifeng Wang, Xuan Wu, Yueying Li, Changdong Zhao, Weiwei Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-09-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.722807/full
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author Junhong Shi
Meiyu Bao
Weifeng Wang
Xuan Wu
Yueying Li
Changdong Zhao
Weiwei Liu
Weiwei Liu
author_facet Junhong Shi
Meiyu Bao
Weifeng Wang
Xuan Wu
Yueying Li
Changdong Zhao
Weiwei Liu
Weiwei Liu
author_sort Junhong Shi
collection DOAJ
description Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 3 (PLOD3) is related to a variety of human diseases. However, its function in Colorectal cancer (CRC) remains uncertain. PLOD3 expression was analyzed using The Cancer Genome Atlas (TCGA) pan-cancer data. DAVID was used for enrichment analysis of PLOD3-related genes. The correlation between PLOD3 expression and immune cell infiltration was evaluated. Four expression profile datasets (GSE17536, GSE39582, GSE74602, and GSE113513) from Gene Expression Omnibus, and two proteomic datasets were used as validation cohorts for assessing the diagnostic and prognostic value of PLOD3 in CRC. What’s more, we performed immunohistochemistry (IHC) staining for PLOD3 in 160 paired CRC specimens and corresponding adjacent non-tumor tissues. PLOD3 was highly expressed in many tumors including CRC. PLOD3 was upregulated in advanced stage CRCs, and high PLOD3 expression was associated with poor survival. High PLOD3 expression was associated with low levels of B cells, CD4+ T cells, M1 macrophages, CD8+ T cells, and multiple immunerelated characteristics. In addition, the high PLOD3 expression group had a higher TIDE score and a lower tumor mutation burden and microsatellite instability, indicating that patients with high PLOD3 expression may be resistant to immunotherapy. Additional datasets and IHC analysis were used to validate the diagnostic and prognostic value of PLOD3 at the mRNA and protein levels in CRC. Patients with non-response to immunotherapy showed increased PLOD3 expression in an immunotherapy treated dataset. PLOD3 is a potential biomarker for CRC diagnosis and prognosis prediction. CRCs with high PLOD3 expression may be resistant to immune checkpoint therapy.
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spelling doaj.art-5fd3f6bd0b4340d78eadfdacfb594f522022-12-21T22:53:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-09-011210.3389/fimmu.2021.722807722807Integrated Profiling Identifies PLOD3 as a Potential Prognostic and Immunotherapy Relevant Biomarker in Colorectal CancerJunhong Shi0Meiyu Bao1Weifeng Wang2Xuan Wu3Yueying Li4Changdong Zhao5Weiwei Liu6Weiwei Liu7Department of Laboratory Medicine and Central Laboratory, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Central Laboratory, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, ChinaDepartment of Central Laboratory, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, ChinaDepartment of Laboratory Medicine and Central Laboratory, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Laboratory Medicine and Central Laboratory, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Gastroenterology, Second People’s Hospital of Lianyungang City, Lianyungang, ChinaDepartment of Laboratory Medicine and Central Laboratory, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Laboratory Medicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, ChinaProcollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 3 (PLOD3) is related to a variety of human diseases. However, its function in Colorectal cancer (CRC) remains uncertain. PLOD3 expression was analyzed using The Cancer Genome Atlas (TCGA) pan-cancer data. DAVID was used for enrichment analysis of PLOD3-related genes. The correlation between PLOD3 expression and immune cell infiltration was evaluated. Four expression profile datasets (GSE17536, GSE39582, GSE74602, and GSE113513) from Gene Expression Omnibus, and two proteomic datasets were used as validation cohorts for assessing the diagnostic and prognostic value of PLOD3 in CRC. What’s more, we performed immunohistochemistry (IHC) staining for PLOD3 in 160 paired CRC specimens and corresponding adjacent non-tumor tissues. PLOD3 was highly expressed in many tumors including CRC. PLOD3 was upregulated in advanced stage CRCs, and high PLOD3 expression was associated with poor survival. High PLOD3 expression was associated with low levels of B cells, CD4+ T cells, M1 macrophages, CD8+ T cells, and multiple immunerelated characteristics. In addition, the high PLOD3 expression group had a higher TIDE score and a lower tumor mutation burden and microsatellite instability, indicating that patients with high PLOD3 expression may be resistant to immunotherapy. Additional datasets and IHC analysis were used to validate the diagnostic and prognostic value of PLOD3 at the mRNA and protein levels in CRC. Patients with non-response to immunotherapy showed increased PLOD3 expression in an immunotherapy treated dataset. PLOD3 is a potential biomarker for CRC diagnosis and prognosis prediction. CRCs with high PLOD3 expression may be resistant to immune checkpoint therapy.https://www.frontiersin.org/articles/10.3389/fimmu.2021.722807/fullColorectal cancerPLOD3biomarkerprognosisimmune therapy
spellingShingle Junhong Shi
Meiyu Bao
Weifeng Wang
Xuan Wu
Yueying Li
Changdong Zhao
Weiwei Liu
Weiwei Liu
Integrated Profiling Identifies PLOD3 as a Potential Prognostic and Immunotherapy Relevant Biomarker in Colorectal Cancer
Frontiers in Immunology
Colorectal cancer
PLOD3
biomarker
prognosis
immune therapy
title Integrated Profiling Identifies PLOD3 as a Potential Prognostic and Immunotherapy Relevant Biomarker in Colorectal Cancer
title_full Integrated Profiling Identifies PLOD3 as a Potential Prognostic and Immunotherapy Relevant Biomarker in Colorectal Cancer
title_fullStr Integrated Profiling Identifies PLOD3 as a Potential Prognostic and Immunotherapy Relevant Biomarker in Colorectal Cancer
title_full_unstemmed Integrated Profiling Identifies PLOD3 as a Potential Prognostic and Immunotherapy Relevant Biomarker in Colorectal Cancer
title_short Integrated Profiling Identifies PLOD3 as a Potential Prognostic and Immunotherapy Relevant Biomarker in Colorectal Cancer
title_sort integrated profiling identifies plod3 as a potential prognostic and immunotherapy relevant biomarker in colorectal cancer
topic Colorectal cancer
PLOD3
biomarker
prognosis
immune therapy
url https://www.frontiersin.org/articles/10.3389/fimmu.2021.722807/full
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