MicroRNA-203 predicts human survival after resection of colorectal liver metastasis

Abstract

BackgroundResection of colorectal liver metastasis (CRLM) can be curative. Predicting which patients may benefit from resection, however, remains challenging. Some microRNAs (miRNAs) become deregulated in cancers and contribute to cancer progression. We hypothesized that miRNA expression can serve as a prognostic marker of survival after CRLM resection.ResultsMiR-203 was significantly overexpressed in tumors of short-term survivors compared to long-term survivors. R1/R2 margin status and high clinical risk score (CRS) were also significantly associated with short-term survival (both p = 0.001). After adjusting for these variables, higher miR-203 expression remained an independent predictor of shorter survival (p = 0.010). In the serum cohort, high CRS and KRAS mutation were significantly associated with short-term survival (p = 0.005 and p = 0.026, respectively). After adjusting for CRS and KRAS status, short-term survivors were found to have significantly higher miR-203 levels (p = 0.016 and p = 0.033, respectively).Materials and MethodsWe employed next-generation sequencing of small-RNAs to profile miRNAs in solid tumors obtained from 38 patients who underwent hepatectomy for CRLM. To validate, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed on 91 tumor samples and 46 preoperative serum samples.ConclusionsAfter CRLM resection, short-term survivors exhibited significantly higher miR-203 levels relative to long-term survivors. MiR-203 may serve as a prognostic biomarker and its prognostic capacity warrants further investigation.

Molecular and Immunohistochemical Markers with Prognostic and Predictive Significance in Liver Metastases from Colorectal Carcinoma

“…Affymetrix microarrays involving 1036 miRNAs were performed in a large study including two pairs of primary CRCs and their matched liver metastases; results were validated using quantitative real-time polymerase chain reaction assay. In particular, 13 miRNAs were deregulated in primary CRCs compared to their matched liver metastases, with a significantly reduced expression of miR-99b-5p, miR-377, and miR-200c, and increased expression of miR-196b-5p in the liver metastasis [ 47 , 49 , 50 ]. In addition, miR-200c and miR-196b-5p were positively correlated with shorter overall survival in patients with liver metastasis [ 51 ].…”

The Contemporary Role of Resection and Ablation in Colorectal Cancer Liver Metastases

“…113,114 Differentially expressed micro-RNAs are also under investigation as potential biomarkers. 115 The examination of systemic therapies such as immune checkpoint inhibitors and regional therapies such as hepatic arterial infusion may lead to improvements in both survival and quality of life. 116,117 The KEYNOTE-177 trial, which is currently active, compares progression-free survival and overall survival in stage IV colorectal cancer patients with either microsatellite instability -high (MSI-H) or mismatch repair deficient (dMMR) tumors receiving pembrolizumab versus standard of care chemotherapy.…”

Thermal Ablation of Metastatic Colon Cancer to the Liver

“…Genetic factors associated with resistance to thermal injury might explain early LTP after CLM ablation and offer a valuable stratification tool to customize treatment. 45,46 Molecular and proliferation markers (Ki67, thymidylate synthase, p53, KRAS, BRAF) improved the ability to predict outcomes after CLM resection [122][123][124][125] and image-guided ablation. 45,46,48 The Ki67 proliferation marker expression has been associated with survival and disease progression after treatment of CLM.…”