Abstract:

Objective Based on the Cancer Genome Atlas（TCGA） database,ferroptosis-related long non-coding RNA（lncRNA） were screened to establish a colon cancer prognostic risk model and to investigate its clinical application role. Methods A total of 48 patients who underwent radical resection of colon cancer were enrolled,and the intraoperatively resected cancer tissues and corresponding paracancerous tissues（2-3 cm from the edge of the cancer tissue）were collected. Transcriptome data of colon cancer（428 cases of colon cancer tissues and 41 cases of normal colon tissues）and clinical data of corresponding patients were collected from the TCGA database. Gene Ontology（GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes（KEGG）pathway analysis were performed for ferroptosis-related genes differentially expressed in colon cancer tissues and normal colon tissues. Screening for ferroptosis-related lncRNA with colon cancer prognosis,consensus clustering analysis was used to classify colon cancer patients and compare overall survival. A prognostic risk model was established by LASSO-Cox regression analysis. A nomogram for predicting overall survival in patients with colon cancer was developed. The biological function of the key lncRNA ITGB1-DT in colon cancer was analyzed by cytological experiments. Results Totally,72 differentially expressed ferroptosis-related genes were screened from the TCGA database,of which 47 cases were up-regulated,and 25 cases were down-regulated. GO enrichment analysis and KEGG pathway analysis showed that these genes were widely involved in biological processes,such as iron metabolism and fatty acid oxidation. A total of 20 ferroptosis-related lncRNA with difference between colon cancer tissues and normal colon tissues were screened. There was statistical significance in overall survival between the 2 colon cancer subgroups classified according to the results of consensus clustering analysis（P<0.001）. According to the results of LASSO-Cox regression analysis,10 lncRNA were screened,and a prognostic risk model was constructed. A total of 428 patients with colon cancer were randomly classified into training group and validation group according to the ratio of 7∶3. In the training group,validation group and overall colon cancer patients,the overall survival rate of high-risk group was lower than that of low-risk group（P<0.001）. The relative expression of ITGB1-DT in colon cancer tissues was higher than that in adjacent tissues（P<0.001）. The results of cytological experiments showed that ITGB1-DT could promote the proliferation of colon cancer cells and inhibit its ferroptosis. Conclusions A colon cancer prognostic risk model based on ferroptosis-related lncRNA has been constructed successfully,and a nomogram that could be used to judge the overall survival rate of colon cancer has been established. ITGB1-DT may promote the development of colon cancer.

Key words: Ferroptosis-related long non-coding RNA, Colon cancer, The Cancer Genome Atlas database