基于转录调控网络预测肺鳞癌风险通路

OBJECTIVE Lung squamous carcinoma,also known as lung squamous cell carcinoma,is a very high incidence and mortality of malignant tumor. The pathogenesis of lung squamous carcinoma is not clear,and we here presented an effective method to identify lung squamous carcinoma risk pathway,helping to elucidate the pathogenesis of lung squamous carcinoma.METHODS We first integrated eight public database resources to obtain regulation data about transcription factor (TF),long non-coding RNA (lncRNA),miRNA and Gene. Then transcriptome sequencing data including TF,lncRNA,miRNA and Gene about lung squamous carcinoma were obtained from TCGA (The Cancer Genome Atlas) data resources. Spearman correlation coefficients were calculated about these regulation relationships,and we got a transcriptional regulatory network associated with lung squamous cell carcinoma. Taking each node with zero in-degree as the starting node,we identified the cascade pathways from the network using the breadth-first search algorithm. Lung cancer related TF,lncRNA,miRNA and Gene were downloaded from disease databases,and we annotated the cascade pathways with lung cancer information. The cascades with high disease annotation rate were regarded as lung squamous carcinoma risk pathways.RESULTS We integrated eight public database resources to retrieve 21 597 candidate regulation relationships, including TF versus lncRNA,miRNA and Gene,lncRNA versus TF and Gene and miRNA versus TF,lncRNA and Gene. After filtering the pairs with spearman correlation coefficients P-value<0.01,we constructed a lung squamous carcinoma related regulatory network,including 2 234 pairs consisted of 91 TFs,552 lncRNAs,125 miRNAs and 937 Genes. By breadth-first search algorithm,we identified 10 941 cascades. After annotated these cascades with lung cancer information,36 cascades with annotation ratio 1 were obtained,and these cascades were deemed as lung squamous carcinoma risk pathways. In the end,we provided nine candidate small molecules for lung squamous carcinoma therapy based on identified risk pathways.CONCLUSION The constructed transcriptional regulation network can help to identify lung squamous carcinoma risk pathways,explain the pathogenesis of lung squamous cell carcinoma and predict the candidate clinical drugs for lung squamous carcinoma therapy.