A coordinate deregulation of microRNAs expressed in mucosa adjacent to tumor predicts relapse after resection in localized colon cancer

Abstract

Up to 20% of colorectal cancer (CRC) node-negative patients develop loco-regional or distant recurrences within 5 years from surgery. No predictive biomarker able to identify the node-negative subjects at high risk of relapse after curative treatment is presently available.Forty-eight localized (i.e. stage I-II) colon cancer patients who underwent radical tumor resection were considered. The expression of five miRNAs, involved in CRC progression, was investigated by qRT-PCR in both tumor tissue and matched normal colon mucosa.Interestingly, we found that the coordinate deregulation of four miRNAs (i.e. miR-18a, miR-21, miR-182 and miR-183), evaluated in the normal mucosa adjacent to tumor, is predictive of relapse within 55 months from curative surgery.Our results, if confirmed in independent studies, may help to identify high-risk patients who could benefit most from adjuvant therapy. Moreover, this work highlights the importance of extending the search for tissue biomarkers also to the tumor-adjacent mucosa.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0770-8) contains supplementary material, which is available to authorized users.

Silencing of miR-182 is associated with modulation of tumorigenesis through apoptosis induction in an experimental model of colorectal cancer

“…In particular, the NABP1 gene, which is involved in the GO “DNA repair” pathway taking part in the apoptotic process, was significantly enriched in the anti-miR-182-treated tumorigenic cell line. Interestingly, a significant NABP1 expression decrease was observed in a pool of primary CRC samples, in which increased miR-182 levels were previously assessed [21], compared to matched normal colon mucosa (Fig. 4c).…”

“…This seems to indicate that the miR-182 upregulation occurs in early premalignant development and is associated with the maintenance of the malignant phenotype [19]. Furthermore, we also demonstrated that high expression levels of miR-182 do not characterize mucosa samples from patients with inflammatory bowel disease, thus suggesting that its deregulation is not a mere consequence of the chronic inflammatory process [21]. Interestingly, in a large functional miRNA screening, Cekaite et al found that miR-182 gene, a component of miRNA cluster miR-183-96-182 located in 7q32 genomic region, is amplified in 26% of primary CRC and 30% of liver metastases [25].…”

“…In reference to CRC development, we identified miR-182-5p (miR-182) as one of the most up-regulated miRNAs in primary tumors compared to normal colon mucosa, thus suggesting its potential impact on target genes de-regulated in CRC [19]. A significant miR-182 increase is observed in the early phases of tumor development and is maintained in the metastatic process [20, 21]. Plasma miR-182 concentrations were higher in CRC patients at stage IV than in controls, and significantly decreased 1 month after radical hepatic metastasectomy, indicating that evaluation of circulating miR-182 may integrate the array of non-invasive blood-based monitoring and screening biomarkers [20].…”

Emerging microRNA biomarkers for colorectal cancer diagnosis and prognosis

“…Moreover, miRNAs from tumour-adjacent mucosa have been studied for the prediction of relapse risk after curative treatment. Four miRNAs (miR-18a, miR-21, miR-182 and miR-183) were found with coordinate deregulation in the normal mucosa adjacent to the tumour, which is predictive of relapse within 55 months from curative surgery in 48 localized CRC patients who underwent radical tumour resection [66].…”

Intratumoral versus Circulating Lymphoid Cells as Predictive Biomarkers in Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: Is the Easiest Path the Best One?

“…Despite the enormous potential of immunotherapy, not all patients or all tumors respond in the same manner to treatment. There are still difficulties to know the best way to select patients that will greatly benefit from this type of therapy, and the only biomarker with clinical utility for immunotherapy, such the expression of PD-L1, which has been studied in many clinical trials [ 6 , 7 , 8 ], is not completely accurate and presents several limitations [ 9 , 10 , 11 ].…”