Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue

Cancers

Alba Costales-Carrera¹  Alberto Muñoz¹  Antonio Barbáchano¹  Luis del Peso¹  Asunción Fernández-Barral¹  Pilar Bustamante-Madrid¹  Ramón Cantero²  Laura Guerra-Pastrián²  Aurora Burgos³  Orlando Domínguez⁴ 

[1] Departamento de Biología del Cáncer, Instituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), 28029 Madrid, Spain;Instituto de Investigación del Hospital Universitario La Paz (IdiPAZ), 28029 Madrid, Spain;Unidad de Endoscopia, Departamento de Digestivo, Hospital Universitario La Paz, 28029 Madrid, Spain;Unidad de Genómica, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain;

关键词: colorectal cancer;    stem cells;    patient-derived organoids;    rectal tumors;    vitamin D;   

DOI  :  10.3390/cancers12082302

来源: DOAJ

【 摘 要 】

Colon and rectal tumors, often referred to as colorectal cancer, show different gene expression patterns in studies that analyze whole tissue biopsies containing a mix of tumor and non-tumor cells. To better characterize colon and rectal tumors, we investigated the gene expression profile of organoids generated from endoscopic biopsies of rectal tumors and adjacent normal colon and rectum mucosa from therapy-naive rectal cancer patients. We also studied the effect of vitamin D on these organoid types. Gene profiling was performed by RNA-sequencing. Organoids from a normal colon and rectum had a shared gene expression profile that profoundly differed from that of rectal tumor organoids. We identified a group of genes of the biosynthetic machinery as rectal tumor organoid-specific, including those encoding the RNA polymerase II subunits POLR2H and POLR2J. The active vitamin D metabolite 1α,25-dihydroxyvitamin D3/calcitriol upregulated stemness-related genes (LGR5, LRIG1, SMOC2, and MSI1) in normal rectum organoids, while it downregulated differentiation marker genes (TFF2 and MUC2). Normal colon and rectum organoids share similar gene expression patterns and respond similarly to calcitriol. Rectal tumor organoids display distinct and heterogeneous gene expression profiles, with differences with respect to those of colon tumor organoids, and respond differently to calcitriol than normal rectum organoids.

【 授权许可】

Unknown