Distinct profiles for mitochondrial t-RNAs and small nucleolar RNAs in locally invasive and metastatic colorectal cancer
A partir d'échantillons de tissu sain et de tissu tumoral prélevés sur 35 patients atteints d'un cancer colorectal localement invasif ou métastatique, cette étude identifie des signatures basées sur l'expression d'ARNs non codants en association avec le stade de la maladie
Purpose: To gain insight into factors involved in tumor progression and metastasis, we examined the role of non-coding RNAs (ncRNAs) in the biological characteristics of colorectal carcinoma (CRC), in paired samples of tumor together with normal mucosa from the same CRC patient. The tumor and healthy tissues samples were collected and stored under stringent conditions, thereby minimizing warm ischemic time.
Experimental Design: We focused particularly on distinctions among high stage tumors and tumors with known metastases, performing RNA-Seq analysis which quantifies transcript abundance and identifies novel transcripts.
Results: In comparing 35 CRCs, including 9 metastatic tumors (metastases to lymph nodes and lymphatic vessels (LN/LV)), to their matched healthy control mucosa, we found a distinct signature of MT-tRNAs and snoRNAs for metastatic and high stage CRC. We also found the following: 1) MT-TF (phenylalanine) and snord12B expression correlated with a substantial number of miRNAs and mRNAs in 14 CRCs examined; 2) a miRNA signature of oxidative stress, hypoxia and a shift to glycolytic metabolism in 14 CRCs, regardless of grade and stage, and 3) heterogeneous MT-tRNA/snoRNA fingerprints for 35 pairs.
Conclusions: These findings could potentially assist in more accurate and predictive staging of CRC including identification of those CRC likely to metastasize.
Clinical Cancer Research , résumé, 2015