Abstract

Inflammation contributing to the underlying progression of diverse human cancers has been generally appreciated, however, explorations into the molecular links between inflammation and cancer in esophagus are still at its early stage. In our study, we presented a functional module-based approach, in combination with multiple data resource (gene expression, protein-protein interactions (PPI), transcriptional and post-transcriptional regulations) to decipher the underlying links. Via mapping differentially expressed disease genes, functional disease modules were identified. As indicated, those common genes and interactions tended to play important roles in linking inflammation and cancer. Based on crosstalk analysis, we demonstrated that, although most disease genes were not shared by both kinds of modules, they might act through participating in the same or similar functions to complete the molecular links. Additionally, we applied pivot analysis to extract significant regulators for per significant crosstalk module pair. As shown, pivot regulators might manipulate vital parts of the module subnetworks, and then work together to bridge inflammation and cancer in esophagus. Collectively, based on our functional module analysis, we demonstrated that shared genes or interactions, significant crosstalk modules, and those significant pivot regulators were served as different functional parts underlying the molecular links between inflammation and cancer in esophagus.

Highlights

  • Inflammation contributing to the underlying progression of diverse human cancers has been generally appreciated, explorations into the molecular links between inflammation and cancer in esophagus are still at its early stage

  • Based on validated cancer genes, we collected from database OMIM11 and DisGeNET12 which organized the data of CTD13, GAD14, RGD13, LHGDN15 and BeFree[16] (Supplementary Table 1), we showed that 38 validated genes were identified as cancer-differentially expressed genes (DEGs) in our data sets, which demonstrated that our identified DEGs were suitable to represent disease conditions

  • Even though the close link between inflammation and cancer has been generally accepted in most human cancers, large-scale explorations based on functional inflammation and cancer modules in esophagus are still lacking

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Summary

Introduction

Inflammation contributing to the underlying progression of diverse human cancers has been generally appreciated, explorations into the molecular links between inflammation and cancer in esophagus are still at its early stage. Via mapping differentially expressed disease genes, functional disease modules were identified As indicated, those common genes and interactions tended to play important roles in linking inflammation and cancer. Based on our functional module analysis, we demonstrated that shared genes or interactions, significant crosstalk modules, and those significant pivot regulators were served as different functional parts underlying the molecular links between inflammation and cancer in esophagus. According to differentially expressed genes (DEGs) identified in oesophagitis and esophageal cancer, we mapped those DEGs to protein-protein interaction (PPI) network, and extracted functional inflammation- and cancer-related modules, respectively. Our functional module-based strategy, help to explore those underlying molecular mechanisms between inflammation and cancer in esophagus, and provide a rich resource for biologists to further design their researches

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