COL10A1 allows stratification of invasiveness of colon cancer and associates to extracellular matrix and immune cell enrichment in the tumor parenchyma.

Kahlert, Ulf D.; Shi, Wenjie; Strecker, Marco; Scherpinski, Lorenz A.; Wartmann, Thomas; Dölling, Maximilian; Perrakis, Aristotelis; Relja, Borna; Mengoni, Miriam; Braun, Andreas; Croner, Roland S.

doi:10.3389/fonc.2022.1007514

by Ulf D. Kahlert, Wenjie Shi, Marco Strecker, Lorenz A. Scherpinski, Thomas Wartmann, Maximilian Dölling, Aristotelis Perrakis, Borna Relja, Miriam Mengoni, Andreas Braun, Roland S. Croner

Abstract:

BACKGROUND: Treatment 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. METHODS: Several 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. RESULTS: COL10A1 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. CONCLUSION: COL10A1 abundance in CRC tissue predicts metastatic and immunogenic properties of the disease. COL10A1 transcription may mediate tumor cell interaction with its stromal microenvironment.

Reference:

COL10A1 allows stratification of invasiveness of colon cancer and associates to extracellular matrix and immune cell enrichment in the tumor parenchyma. (Ulf D. Kahlert, Wenjie Shi, Marco Strecker, Lorenz A. Scherpinski, Thomas Wartmann, Maximilian Dölling, Aristotelis Perrakis, Borna Relja, Miriam Mengoni, Andreas Braun, Roland S. Croner), In Frontiers in oncology, volume 12, 2022.

Bibtex Entry:

@article{kahlert_col10a1_2022,
	title = {{COL}10A1 allows stratification of invasiveness of colon cancer and associates to  extracellular matrix and immune cell enrichment in the tumor parenchyma.},
	volume = {12},
	copyright = {Copyright © 2022 Kahlert, Shi, Strecker, Scherpinski, Wartmann, Dölling,  Perrakis, Relja, Mengoni, Braun and Croner.},
	issn = {2234-943X 2234-943X 2234-943X},
	doi = {10.3389/fonc.2022.1007514},
	abstract = {BACKGROUND: Treatment 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. METHODS:  Several 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. RESULTS: COL10A1 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. CONCLUSION: COL10A1  abundance in CRC tissue predicts metastatic and immunogenic properties of the  disease. COL10A1 transcription may mediate tumor cell interaction with its  stromal microenvironment.},
	language = {eng},
	journal = {Frontiers in oncology},
	author = {Kahlert, Ulf D. and Shi, Wenjie and Strecker, Marco and Scherpinski, Lorenz A. and Wartmann, Thomas and Dölling, Maximilian and Perrakis, Aristotelis and Relja, Borna and Mengoni, Miriam and Braun, Andreas and Croner, Roland S.},
	year = {2022},
	pmid = {36267978},
	pmcid = {PMC9577326},
	keywords = {biomarker, collagen type 10, colon cancer, Prognosis, Tumor Microenvironment},
	pages = {1007514}
}