| Research objective:Colon cancer is a common malignant tumor in the digestive tract system.More and more studies have shown that colon cancer is the result of the combined action of environmental,diet,lifestyle and genetic factors[1].A range of treatments including surgery,chemotherapy,targeted therapy,radiotherapy and immunotherapy can affect a patient’s prognosis.However,the prognosis of patients with advanced colon cancer is still poor[2].Genomic instability has long been considered as one of the hallmarks of most cancers,which is closely related to tumor progression and chemotherapy drug resistance.This study aims to explore genomic instability associated LncRNAs and their clinical prognostic and therapeutic potential in colon cancer.Methods:The R package "limma" was used for difference analysis,and the setting criteria was:multiple of difference(Fold change)>2 or<0.5,error detection rate(FDR)<0.05.Univariate COX analysis was used to evaluate the relationship between long non-coding RNA(LncRNAs)and prognosis,and multivariate COX proportional risk regression was used to analyze prognostic associated LncRNAs associated with genomic instability and to construct prognostic risk model.The median risk score obtained by the model divided the patients into a high risk group and a low risk group.The difference in prognosis between the two groups was evaluated using Kaplan-Meier method and tested for significance using log-RANk.The efficiency of the prognostic model was evaluated by the area under the time-dependent receiver operating characteristic(ROC)curve.The expression levels of LncRNAs associated with the protective factors of patient prognosis were detected by qPCR in the samples.Prediction of anti cancer drug response in high-and low-risk patients using the R-pack"pRRophetic".The "pRRophetic" algorithm uses ridge regression to estimate the semi-suppressed concentration(IC50)of the drug per patient,and uses a ten-fold crossover for internal validation.The "pRRophetic" calculation is based on the Cancer Drug Sensitivity Genomics(GDSC)database.The R software package rms is used to build a line graph and calculate the consistency index(C-index)of the line graph.Results:A total of 435 LncRNAs associated with genomic instability were obtained(169 down-regulated and 266 up-regulated),among which 22 were associated with the prognosis of patients,2(AC115989.1 and AL096803.3)were protective factors for prognosis of patients with colon cancer,and 20 were risk factors for prognosis.After testing the specimen by qPCR.We found that the expression level of prognostic protective LncRNAs in colon cancer tissues was significantly lower than that in adjacent colon cancer tissues.We constructed a prognostic risk model consisting of eight LncRNAs associated with genomic instability,and patients with high risk scores had worse prognosis and shorter median survival.The area under ROC curve(AUC)for five-year survival predicted by this model was 0.823 in the training set,0.722 in the validation set,and 0.759 in the overall TCGA colon cancer patient population.Patients with low risk scores had lower half-suppression concentrations(IC50)of cisplatin and higher sensitivity(P<0.0001).Conclusions:Based on bioinformatics analysis,we identified LncRNAs associated with genomic instability in colon cancer and constructed and validated a prognostic risk model consisting of eight LncRNAs associated with genomic instability.This model can predict cisplatin drug sensitivity.By combining the tumor stage and the prognosis model,we constructed a histogram,which was better than the traditional histopathological features and the previous prognosis model in predicting the five-year survival of colon cancer patients. |
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