Abstract

BackgroundFeed-forward loops (FFLs), consisting of miRNAs, transcription factors (TFs) and their common target genes, have been validated to be important for the initialization and development of complex diseases, including cancer. Esophageal Carcinoma (ESCA) and Stomach Adenocarcinoma (STAD) are two types of malignant tumors in the digestive tract. Understanding common and distinct molecular mechanisms of ESCA and STAD is extremely crucial.ResultsIn this paper, we presented a computational framework to explore common and distinct FFLs, and molecular biomarkers for ESCA and STAD. We identified FFLs by combining regulation pairs and RNA-seq data. Then we constructed disease-specific co-expression networks based on the FFLs identified. We also used random walk with restart (RWR) on disease-specific co-expression networks to prioritize candidate molecules. We identified 148 and 242 FFLs for these two types of cancer, respectively. And we found that one TF, E2F3 was related to ESCA, two genes, DTNA and KCNMA1 were related to STAD, while one TF ESR1 and one gene KIT were associated with both of the two types of cancer.ConclusionsThis proposed computational framework predicted disease-related biomolecules effectively and discovered the correlation between two types of cancers, which helped develop the diagnostic and therapeutic strategies of Esophageal Carcinoma and Stomach Adenocarcinoma.

Highlights

  • Feed-forward loops (FFLs), consisting of miRNAs, transcription factors (TFs) and their common target genes, have been validated to be important for the initialization and development of complex diseases, including cancer

  • Random walk with restart (RWR) was used to calculate the score of each biomolecule in the co-expression networks

  • We further investigated the common FFLs in the Esophageal Carcinoma (ESCA)-specific FFL and Stomach Adenocarcinoma (STAD)-specific FFL, and found that there were 3 TFP-FFLs, 8 TFN-FFLs, and 41 miRNAN-FFLs

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Summary

Introduction

Feed-forward loops (FFLs), consisting of miRNAs, transcription factors (TFs) and their common target genes, have been validated to be important for the initialization and development of complex diseases, including cancer. Esophageal Carcinoma (ESCA) and Stomach Adenocarcinoma (STAD) are two types of malignant tumors in the digestive tract. Understanding common and distinct molecular mechanisms of ESCA and STAD is extremely crucial. Esophageal Carcinoma (ESCA) and Stomach Adenocarcinoma (STAD) are two types of cancer in the digestive tract. ESCA ranks sixth in its cancer-related mortality rate [1, 2]. Stomach Adenocarcinoma is one of common malignancies of digestive tract [4, 5]. Despite the advances in the treatment of STAD, the 5-year survival rate is 5~15% [6]. Both ESCA and STAD belong to digestive tract cancer, and the sites of their incidence

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