Abstract
Colorectal cancer (CRC) is the fourth-ranked cause of cancer-related deaths worldwide. Despite recent advances in CRC management, distant recurrence (DR) remains the major cause of mortality in patients with preoperative chemotherapy and radiotherapy, underscoring a need to precisely identify novel gene signatures for predicting the risk of systemic relapse. Herein, we integrated two independent CRC gene expression datasets: the GSE71222 dataset, including 26 patients who developed DR and 126 patients who did not develop DR, and the GSE21510 dataset, including 23 patients who developed DR and 76 patients who did not develop DR. Our data revealed 37 common upregulated genes (fold change (FC) ≥ 1.5, P < 0.05) and three common downregulated genes (FC ≤ 1.5, P < 0.05) between DR and non-recurrent patients from the two datasets. We subsequently validated the upregulated gene panel in the Cancer Genome Atlas CRC datasets (379 patients), which identified a five-gene signature (S100A2, VIP, HOXC6, DACT1, KIF26B) associated with poor overall survival (OS, log-rank test P-value: 1.19 × 10−4) and poor disease-free survival (DFS, log-rank test P-value: 0.002). In a Cox proportional hazards multiple regression model, the five-gene signature and tumor stage retained their significance as independent prognostic factors for CRC DFS and OS. Therefore, our data identified a novel DR gene expression signature associated with worse prognosis in CRC.
Highlights
Colorectal cancer (CRC) is one of the most prevalent types of cancers and is currently ranked as the fourth leading cause of cancer-related deaths globally, and the third leading cause of death in the United States in both men and women [1, 2]
To devise a gene expression panel associated with CRC distant recurrence (DR) with high confidence, we analyzed two independent CRC gene expression datasets (GSE71222 and GSE21510) and identified the genes associated with patient recurrence
We subsequently focused on the potential role of the upregulated genes in CRC recurrence
Summary
Colorectal cancer (CRC) is one of the most prevalent types of cancers and is currently ranked as the fourth leading cause of cancer-related deaths globally, and the third leading cause of death in the United States in both men and women [1, 2]. Multiple molecular alterations occur during CRC development and progression. Gene Expression Signature for CRC Distant Recurrence clinical and pathological parameters that can accurately predict the prognosis of patients with CRC has been a daunting task. Over the past several years, numerous molecular signatures have been identified for CRC prognosis [5,6,7]. One major problem with many of the established molecular signatures for CRC relapse is the lack of validation across different groups and platforms. Large-scale analysis of multiple gene expression datasets might lead to the identification of more representative gene expression signatures associated with CRC relapse. We integrated three independent CRC gene expression datasets retrospectively, which led to the identification of a novel five-gene signature associated with CRC systemic relapse
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