COL10A1 allows stratification of invasiveness of colon cancer and associates to extracellular matrix and immune cell enrichment in the tumor parenchyma
BackgroundTreatment options for metastatic colorectal cancer (CRC) are mostly ineffective. We present new evidence that tumor tissue collagen type X alpha 1 (COL10A1) is a relevant candidate biomarker to improve this dilemma.MethodsSeveral public databases had been screened to observe COL10A1 expres...
Main Authors: | , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2022-10-01
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Series: | Frontiers in Oncology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1007514/full |
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author | Ulf D. Kahlert Wenjie Shi Wenjie Shi Marco Strecker Lorenz A. Scherpinski Thomas Wartmann Maximilian Dölling Aristotelis Perrakis Borna Relja Miriam Mengoni Andreas Braun Roland S. Croner |
author_facet | Ulf D. Kahlert Wenjie Shi Wenjie Shi Marco Strecker Lorenz A. Scherpinski Thomas Wartmann Maximilian Dölling Aristotelis Perrakis Borna Relja Miriam Mengoni Andreas Braun Roland S. Croner |
author_sort | Ulf D. Kahlert |
collection | DOAJ |
description | BackgroundTreatment options for metastatic colorectal cancer (CRC) are mostly ineffective. We present new evidence that tumor tissue collagen type X alpha 1 (COL10A1) is a relevant candidate biomarker to improve this dilemma.MethodsSeveral public databases had been screened to observe COL10A1 expression in transcriptome levels with cell lines and tissues. Protein interactions and alignment to changes in clinical parameters and immune cell invasion were performed, too. We also used algorithms to build a novel COL10A1-related immunomodulator signature. Various wet-lab experiments were conducted to quantify COL10A1 protein and transcript expression levels in disease and control cell models.ResultsCOL10A1 mRNA levels in tumor material is clinical and molecular prognostic, featuring upregulation compared to non-cancer tissue, increase with histomorphological malignancy grading of the tumor, elevation in tumors that invade perineural areas, or lymph node invasion. Transcriptomic alignment noted a strong positive correlation of COL10A1 with transcriptomic signature of cancer-associated fibroblasts (CAFs) and populations of the immune compartment, namely, B cells and macrophages. We verified those findings in functional assays showing that COL10A1 are decreased in CRC cells compared to fibroblasts, with strongest signal in the cell supernatant of the cells.ConclusionCOL10A1 abundance in CRC tissue predicts metastatic and immunogenic properties of the disease. COL10A1 transcription may mediate tumor cell interaction with its stromal microenvironment. |
first_indexed | 2024-04-11T09:15:59Z |
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institution | Directory Open Access Journal |
issn | 2234-943X |
language | English |
last_indexed | 2024-04-11T09:15:59Z |
publishDate | 2022-10-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Oncology |
spelling | doaj.art-64c90254752346648c3f9a32f104014b2022-12-22T04:32:20ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-10-011210.3389/fonc.2022.10075141007514COL10A1 allows stratification of invasiveness of colon cancer and associates to extracellular matrix and immune cell enrichment in the tumor parenchymaUlf D. Kahlert0Wenjie Shi1Wenjie Shi2Marco Strecker3Lorenz A. Scherpinski4Thomas Wartmann5Maximilian Dölling6Aristotelis Perrakis7Borna Relja8Miriam Mengoni9Andreas Braun10Roland S. Croner11University Clinic for General, Visceral, Vascular and Transplantation Surgery, Faculty of Medicine, Otto-von-Guericke-University, Magdeburg, GermanyUniversity Clinic for General, Visceral, Vascular and Transplantation Surgery, Faculty of Medicine, Otto-von-Guericke-University, Magdeburg, GermanyUniversity Hospital for Gynecology, Pius-Hospital, University Medicine Oldenburg, Oldenburg, GermanyUniversity Clinic for General, Visceral, Vascular and Transplantation Surgery, Faculty of Medicine, Otto-von-Guericke-University, Magdeburg, GermanyUniversity Clinic for General, Visceral, Vascular and Transplantation Surgery, Faculty of Medicine, Otto-von-Guericke-University, Magdeburg, GermanyUniversity Clinic for General, Visceral, Vascular and Transplantation Surgery, Faculty of Medicine, Otto-von-Guericke-University, Magdeburg, GermanyUniversity Clinic for General, Visceral, Vascular and Transplantation Surgery, Faculty of Medicine, Otto-von-Guericke-University, Magdeburg, GermanyUniversity Clinic for General, Visceral, Vascular and Transplantation Surgery, Faculty of Medicine, Otto-von-Guericke-University, Magdeburg, GermanyExperimental Radiology, University Clinic of Radiology and Nuclear Medicine, Faculty of Medicine, Otto-von-Guericke-University, Magdeburg, GermanyUniversity Clinic for Dermatology, Faculty of Medicine, Otto-von-Guericke-University, Magdeburg, GermanyUniversity Clinic for Dermatology, Faculty of Medicine, Otto-von-Guericke-University, Magdeburg, GermanyUniversity Clinic for General, Visceral, Vascular and Transplantation Surgery, Faculty of Medicine, Otto-von-Guericke-University, Magdeburg, GermanyBackgroundTreatment options for metastatic colorectal cancer (CRC) are mostly ineffective. We present new evidence that tumor tissue collagen type X alpha 1 (COL10A1) is a relevant candidate biomarker to improve this dilemma.MethodsSeveral public databases had been screened to observe COL10A1 expression in transcriptome levels with cell lines and tissues. Protein interactions and alignment to changes in clinical parameters and immune cell invasion were performed, too. We also used algorithms to build a novel COL10A1-related immunomodulator signature. Various wet-lab experiments were conducted to quantify COL10A1 protein and transcript expression levels in disease and control cell models.ResultsCOL10A1 mRNA levels in tumor material is clinical and molecular prognostic, featuring upregulation compared to non-cancer tissue, increase with histomorphological malignancy grading of the tumor, elevation in tumors that invade perineural areas, or lymph node invasion. Transcriptomic alignment noted a strong positive correlation of COL10A1 with transcriptomic signature of cancer-associated fibroblasts (CAFs) and populations of the immune compartment, namely, B cells and macrophages. We verified those findings in functional assays showing that COL10A1 are decreased in CRC cells compared to fibroblasts, with strongest signal in the cell supernatant of the cells.ConclusionCOL10A1 abundance in CRC tissue predicts metastatic and immunogenic properties of the disease. COL10A1 transcription may mediate tumor cell interaction with its stromal microenvironment.https://www.frontiersin.org/articles/10.3389/fonc.2022.1007514/fullcolon cancerbiomarkertumor microenvironmentcollagen type 10prognosis |
spellingShingle | Ulf D. Kahlert Wenjie Shi Wenjie Shi Marco Strecker Lorenz A. Scherpinski Thomas Wartmann Maximilian Dölling Aristotelis Perrakis Borna Relja Miriam Mengoni Andreas Braun Roland S. Croner COL10A1 allows stratification of invasiveness of colon cancer and associates to extracellular matrix and immune cell enrichment in the tumor parenchyma Frontiers in Oncology colon cancer biomarker tumor microenvironment collagen type 10 prognosis |
title | COL10A1 allows stratification of invasiveness of colon cancer and associates to extracellular matrix and immune cell enrichment in the tumor parenchyma |
title_full | COL10A1 allows stratification of invasiveness of colon cancer and associates to extracellular matrix and immune cell enrichment in the tumor parenchyma |
title_fullStr | COL10A1 allows stratification of invasiveness of colon cancer and associates to extracellular matrix and immune cell enrichment in the tumor parenchyma |
title_full_unstemmed | COL10A1 allows stratification of invasiveness of colon cancer and associates to extracellular matrix and immune cell enrichment in the tumor parenchyma |
title_short | COL10A1 allows stratification of invasiveness of colon cancer and associates to extracellular matrix and immune cell enrichment in the tumor parenchyma |
title_sort | col10a1 allows stratification of invasiveness of colon cancer and associates to extracellular matrix and immune cell enrichment in the tumor parenchyma |
topic | colon cancer biomarker tumor microenvironment collagen type 10 prognosis |
url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1007514/full |
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