MiR-30a and miR-200c differentiate cholangiocarcinomas from gastrointestinal cancer liver metastases.

Jun Won Park,Soo Young Cho,Dong Ho Choi,Sang Jae Park,Hark Kyun Kim,Jong Min Jeong,Jae Hee Cheon,Kye Soo Cho,Sripathi M Sureban

doi:10.1371/journal.pone.0250083

Abstract

Prior studies have demonstrated the utility of microRNA assays for predicting some cancer tissue origins, but these assays need to be further optimized for predicting the tissue origins of adenocarcinomas of the liver. We performed microRNA profiling on 195 frozen primary tumor samples using 14 types of tumors that were either adenocarcinomas or differentiated from adenocarcinomas. The 1-nearest neighbor method predicted tissue-of-origin in 33 samples of a test set, with an accuracy of 93.9% at feature selection p values ranging from 10−4 to 10−10. According to binary decision tree analyses, the overexpression of miR-30a and the underexpression of miR-200 family members (miR-200c and miR-141) differentiated intrahepatic cholangiocarcinomas from extrahepatic adenocarcinomas. When binary decision tree analyses were performed using the test set, the prediction accuracy was 84.8%. The overexpression of miR-30a and the reduced expressions of miR-200c, miR-141, and miR-425 could distinguish intrahepatic cholangiocarcinomas from liver metastases from the gastrointestinal tract.

Highlights

Being able to predict where a metastatic tissue originated from is important for the clinical management of patients with metastatic cancers, and microRNA profiling has been used successfully to predict the tissue-of-origin for metastases [1,2,3,4,5]
When microRNAs that were differentially expressed among the 195 primary tumors in the training set were applied to the test set of liver metastasectomy samples, the prediction accuracy was consistently 93.9% at p values ranging from 10–4 to 10–10
This study suggests that microRNA profiles can distinguish between intrahepatic cholangiocarcinomas and extrahepatic cancers of the digestive system, which is often difficult due to the lack of validated tissue-specific biomarkers for cholangiocarcinoma

Summary

Introduction

Being able to predict where a metastatic tissue originated from is important for the clinical management of patients with metastatic cancers, and microRNA profiling has been used successfully to predict the tissue-of-origin for metastases [1,2,3,4,5]. Rosenfeld et al reported a prediction accuracy of 89% using the first-generation of Rosetta Genomics microRNA assays [2]. Using assays based on 47 microRNAs, Ferracin et al reported prediction accuracies of 100% and 78% for primary cancers and metastases, respectively [4]. Sokilde et al reported that their 132 microRNA-based assays correctly predicted tissue-of-origin in 88% of metastases [5]. While these prior microarray studies have demonstrated the utility of microRNA assays for predicting cancer tissue-of-

Methods

Results

Conclusion