Published online Nov 14, 2019. doi: 10.3748/wjg.v25.i42.6322
Peer-review started: September 3, 2019
First decision: October 14, 2019
Revised: October 29, 2019
Accepted: November 7, 2019
Article in press: November 7, 2019
Published online: November 14, 2019
Nonalcoholic steatohepatitis-related cirrhosis is one of the liver complications in type 2 diabetes mellitus (T2DM) and reported to be a risk factor for developing hepatocellular carcinoma (HCC). A reliable screening biomarker of liver cirrhosis (LC) and HCC among T2DM patients is important to reduce the morbidity and mortality of this disease. MicroRNA (miRNA) is considered a key player in HCC and T2DM, and it might be a hidden culprit in diabetes-associated HCC, making it a promising reliable prognostic tool.
To investigate the signature of serum miRNAs as early biomarkers for the screening of HCC among diabetic patients.
Expression profiles of miRNAs in serum samples of diabetic LC and diabetic HCC patients were assessed using Illumina sequencing; then, RT-qPCR was used to validate significantly altered miRNAs between the two groups. Candidate miRNAs were tested in serum samples of 200 T2DM patients, 270 LC patients, 200 HCC patients, and 225 healthy control subjects. Additionally, receiver operating characteristic (ROC) analysis, with area under the curve (AUC), was performed to assess the diagnostic performance of the screened miRNAs for discriminating HCC from LC and nonmalignant patients (LC + T2DM).
Expression of the sequenced miRNAs in serum was different in HCC vs LC-positive T2DM patients. Two miRNAs (miR-34a, miR-221) were significantly up-regulated and five miRNAs (miR-16, miR-23-3p, miR-122-5p, miR-198, miR-199a-3p) were significantly down-regulated in HCC compared to LC patients. Analysis of ROC curve demonstrated that the combination of these seven miRNAs can be used as a reliable biomarker for detection of HCC in diabetic patients, as it could identify HCC with high diagnostic accuracy in diabetic LC patients (AUC = 0.993) and in diabetic nonmalignant patients (AUC = 0.961).
This study validates a panel of serum miRNAs that can be used as a reliable noninvasive screening biomarker of HCC among T2DM cirrhotic and noncirrhotic patients. The study recommends further research to shed light on a possible role of c-Met in T2DM-associated HCC via the miRNA regulatory pathway.
Core tip: The identification of high-sensitivity biomarkers for detection of he-patocellular carcinoma (HCC) in high-risk individuals is essential. The present study was undertaken to identify and validate serum microRNAs as potential biomarkers for HCC among type 2 diabetes patients.