Integrated gene expression signature analysis of prognosis and drug-resistance in patients with serrated colorectal adenocarcinoma / 第二军医大学学报

ABSTRACT

Objective: To conduct a integrated analysis of gene expression signature and gene expression profile, so as to provide reference for the prognosis and drug-resistance of serrated colorectal adenocarcinoma (SCA). Methods: We downloaded four gene expression datasets (GSE14333, GSE17538, GSE33113, and GSE37892) of colorectal carcinoma with the follow-up survival data from GEO database, and then integrated them into a entire expression profile (n=600) with batch adjustment and gene expression value extraction. An SCA gene signature and the corresponding expression profile were integrated with the previous expression dataset. Using the gene signature score model we assigned score to each patient in the gene expression dataset and classified the patients into serrated, transitional, or conventional subtypes. Kaplan-Meier analysis and Cox model were used to compare the risks of cancer recurrence between three subtypes of colorectal carcinoma. Gene signature model were also used to generate the score for each patient in the datasets associated with alleviative therapy of colorectal cancer (GSE28702, GSE5851). The SCA drug-resistance was analyzed by observing the therapeutic effective group and non-effective group. Results: According to cut-off value of CRC subtypes, 600 patients in the combined dataset were classified as 50 with serrated subtype, 126 with transitional subtype, and 424 with conventional subtype. Survival analysis showed the serrated and transitional subtypes had very similar scores to predict patient survival, and they were also independent risk factors for postoperative recurrence. When comparing serrated and conventional subtypes, multivariate Cox model analysis indicated the patients with serrated subtype was an unfavorable independent risk factor for prognosis (AHR=1.792, 95%CI 1.011-3.177). Responders to cetuximab treatment had significantly higher signature scores than non-responders (P=0.017), while responders to FOLFOX treatment had similar signature scores with the non-responders. Conclusion: Serrated subtype is an independent risk factor of postoperative recurrence in SCA patients, and is related to the treatment with cetuximab.