Pathological features and prognosis based on microsatellite stability status in colorectal cancer patients: a...

Colorectal cancer (CRC) is one of the most common and life-threatening intestinal tumors throughout the world. Its incidence and mortality have been going up in recent decades, and more accurate and personalized treatment for CRC are also being developed continuously. Early screening, molecular typing, and risk grouping have become critical for improving patient survival by using sensitive and special biological markers.

We analyzed the expression of four mismatch repair (MMR) genes, namely MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), and PMS1 homolog 2 (PMS2), in CRC and normal tissues using the Tumor, Normal and Metastatic (TNM plot) database. We used the Kaplan-Meier analysis for prognosis, and related pathways were annotated by the Kyoto Encyclopedia of Genes and Genomes. We conducted a retrospective study with 115 CRC patients, who were divided into microsatellite stable (MSS) and microsatellite instability (MSI) groups by immunohistochemistry (IHC). The diagnostic value of MMR markers was assessed through receiver operating characteristic (ROC) curve analysis.

Online data showed that MMR genes were more highly expressed in CRC than in the normal group (P<0.05). Low expression of these genes was linked to shorter recurrence free survival (RFS, P<0.05), and the related signaling pathways also exert an impact on cell cycle regulation. In clinical samples, loss of MLH1 expression was found in female patients, those aged ≥60 years and lymph node-negative cases (P<0.05). MSI-positive tumors were mostly located in the right-sided colon (P<0.05). The combined model of MSH6 and PMS2 had the highest area under the curve (AUC) of 0.981 (95% confidence interval (CI): 0.936-0.997, P<0.001).

Combined detection of MSH6 and PMS2 serves as a reliable biomarker for determining the microsatellite status in CRC. This study provides a basis for the precise diagnosis and targeted therapy of CRC.