date: 2022-03-31T06:25:33Z pdf:unmappedUnicodeCharsPerPage: 17 pdf:PDFVersion: 1.7 pdf:docinfo:title: Elevated MACC1 Expression in Colorectal Cancer Is Driven by Chromosomal Instability and Is Associated with Molecular Subtype and Worse Patient Survival xmp:CreatorTool: LaTeX with hyperref Keywords: CRC; MACC1; gene copy number alteration; gene expression; survival access_permission:modify_annotations: true access_permission:can_print_degraded: true subject: 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. dc:creator: Vincent Vuaroqueaux, Alexandra Musch, Dennis Kobelt, Thomas Risch, Pia Herrmann, Susen Burock, Anne-Lise Peille, Marie-Laure Yaspo, Heinz-Herbert Fiebig and Ulrike Stein dcterms:created: 2022-03-29T16:14:59Z Last-Modified: 2022-03-31T06:25:33Z dcterms:modified: 2022-03-31T06:25:33Z dc:format: application/pdf; version=1.7 title: Elevated MACC1 Expression in Colorectal Cancer Is Driven by Chromosomal Instability and Is Associated with Molecular Subtype and Worse Patient Survival Last-Save-Date: 2022-03-31T06:25:33Z pdf:docinfo:creator_tool: LaTeX with hyperref access_permission:fill_in_form: true pdf:docinfo:keywords: CRC; MACC1; gene copy number alteration; gene expression; survival pdf:docinfo:modified: 2022-03-31T06:25:33Z meta:save-date: 2022-03-31T06:25:33Z pdf:encrypted: false dc:title: Elevated MACC1 Expression in Colorectal Cancer Is Driven by Chromosomal Instability and Is Associated with Molecular Subtype and Worse Patient Survival modified: 2022-03-31T06:25:33Z cp:subject: 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. pdf:docinfo:subject: 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. Content-Type: application/pdf pdf:docinfo:creator: Vincent Vuaroqueaux, Alexandra Musch, Dennis Kobelt, Thomas Risch, Pia Herrmann, Susen Burock, Anne-Lise Peille, Marie-Laure Yaspo, Heinz-Herbert Fiebig and Ulrike Stein X-Parsed-By: org.apache.tika.parser.DefaultParser creator: Vincent Vuaroqueaux, Alexandra Musch, Dennis Kobelt, Thomas Risch, Pia Herrmann, Susen Burock, Anne-Lise Peille, Marie-Laure Yaspo, Heinz-Herbert Fiebig and Ulrike Stein meta:author: Vincent Vuaroqueaux, Alexandra Musch, Dennis Kobelt, Thomas Risch, Pia Herrmann, Susen Burock, Anne-Lise Peille, Marie-Laure Yaspo, Heinz-Herbert Fiebig and Ulrike Stein dc:subject: CRC; MACC1; gene copy number alteration; gene expression; survival meta:creation-date: 2022-03-29T16:14:59Z created: 2022-03-29T16:14:59Z access_permission:extract_for_accessibility: true access_permission:assemble_document: true xmpTPg:NPages: 17 Creation-Date: 2022-03-29T16:14:59Z pdf:charsPerPage: 4006 access_permission:extract_content: true access_permission:can_print: true meta:keyword: CRC; MACC1; gene copy number alteration; gene expression; survival Author: Vincent Vuaroqueaux, Alexandra Musch, Dennis Kobelt, Thomas Risch, Pia Herrmann, Susen Burock, Anne-Lise Peille, Marie-Laure Yaspo, Heinz-Herbert Fiebig and Ulrike Stein producer: pdfTeX-1.40.21 access_permission:can_modify: true pdf:docinfo:producer: pdfTeX-1.40.21 pdf:docinfo:created: 2022-03-29T16:14:59Z