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Article

Elevated MACC1 Expression in Colorectal Cancer Is Driven by Chromosomal Instability and Is Associated with Molecular Subtype and Worse Patient Survival

1
4HF Biotec GmbH, Am Flughafen 14, 79108 Freiburg, Germany
2
Experimental and Clinical Research Center, Charité–Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany
3
German Cancer Consortium (DKTK), 69120 Heidelberg, Germany
4
Otto Warburg Laboratory “Gene Regulation and Systems Biology of Cancer”, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany
5
Charité Comprehensive Cancer Center, 10117 Berlin, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Jesús García-Foncillas
Cancers 2022, 14(7), 1749; https://doi.org/10.3390/cancers14071749
Received: 21 February 2022 / Revised: 21 March 2022 / Accepted: 28 March 2022 / Published: 29 March 2022
(This article belongs to the Special Issue Biomarker in Metastatic Colorectal Cancer)
Elevated expression of Metastasis-Associated in Colon Cancer 1 (MACC1) has been identified as a strong prognostic marker of adverse outcomes for human colorectal (CRC) and other solid cancers. The biological basis of high MACC1 expression and the context of its occurrence are still poorly understood. This study investigated whether chromosomal instability and somatic copy number alterations (SCNA) frequently occurring in CRC contribute to MACC1 dysregulation, with prognostic and predictive impact.
Metastasis-Associated in Colon Cancer 1 (MACC1) is a strong prognostic biomarker inducing proliferation, migration, invasiveness, and metastasis of cancer cells. The context of MACC1 dysregulation in cancers is, however, still poorly understood. Here, we investigated whether chromosomal instability and somatic copy number alterations (SCNA) frequently occurring in CRC contribute to MACC1 dysregulation, with prognostic and predictive impacts. Using the Oncotrack and Charité CRC cohorts of CRC patients, we showed that elevated MACC1 mRNA expression was tightly dependent on increased MACC1 gene SCNA and was associated with metastasis and shorter metastasis free survival. Deep analysis of the COAD-READ TCGA cohort revealed elevated MACC1 expression due to SCNA for advanced tumors exhibiting high chromosomal instability (CIN), and predominantly classified as CMS2 and CMS4 transcriptomic subtypes. For that cohort, we validated that elevated MACC1 mRNA expression correlated with reduced disease-free and overall survival. In conclusion, this study gives insights into the context of MACC1 expression in CRC. Increased MACC1 expression is largely driven by CIN, SCNA gains, and molecular subtypes, potentially determining the molecular risk for metastasis that might serve as a basis for patient-tailored treatment decisions. View Full-Text
Keywords: CRC; MACC1; gene copy number alteration; gene expression; survival CRC; MACC1; gene copy number alteration; gene expression; survival
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MDPI and ACS Style

Vuaroqueaux, V.; Musch, A.; Kobelt, D.; Risch, T.; Herrmann, P.; Burock, S.; Peille, A.-L.; Yaspo, M.-L.; Fiebig, H.-H.; Stein, U. Elevated MACC1 Expression in Colorectal Cancer Is Driven by Chromosomal Instability and Is Associated with Molecular Subtype and Worse Patient Survival. Cancers 2022, 14, 1749. https://doi.org/10.3390/cancers14071749

AMA Style

Vuaroqueaux V, Musch A, Kobelt D, Risch T, Herrmann P, Burock S, Peille A-L, Yaspo M-L, Fiebig H-H, Stein U. Elevated MACC1 Expression in Colorectal Cancer Is Driven by Chromosomal Instability and Is Associated with Molecular Subtype and Worse Patient Survival. Cancers. 2022; 14(7):1749. https://doi.org/10.3390/cancers14071749

Chicago/Turabian Style

Vuaroqueaux, Vincent, Alexandra Musch, Dennis Kobelt, Thomas Risch, Pia Herrmann, Susen Burock, Anne-Lise Peille, Marie-Laure Yaspo, Heinz-Herbert Fiebig, and Ulrike Stein. 2022. "Elevated MACC1 Expression in Colorectal Cancer Is Driven by Chromosomal Instability and Is Associated with Molecular Subtype and Worse Patient Survival" Cancers 14, no. 7: 1749. https://doi.org/10.3390/cancers14071749

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