A prognostic index based on an eleven gene signature to predict systemic recurrences in colorectal cancer

Abstract

Approximately half of colorectal cancer (CRC) patients experience disease recurrence and metastasis, and these individuals frequently fail to respond to treatment due to their clinical and biological diversity. Here, we aimed to identify a prognostic signature consisting of a small gene group for precisely predicting CRC heterogeneity. We performed transcriptomic profiling using RNA-seq data generated from the primary tissue samples of 130 CRC patients. A prognostic index (PI) based on recurrence-associated genes was developed and validated in two larger independent CRC patient cohorts (n = 795). The association between the PI and prognosis of CRC patients was evaluated using Kaplan–Meier plots, log-rank tests, a Cox regression analysis and a RT-PCR analysis. Transcriptomic profiling in 130 CRC patients identified two distinct subtypes associated with systemic recurrence. Pathway enrichment and RT-PCR analyses revealed an eleven gene signature incorporated into the PI system, which was a significant prognostic indicator of CRC. Multivariate and subset analyses showed that PI was an independent risk factor (HR = 1.812, 95% CI = 1.342–2.448, P < 0.001) with predictive value to identify low-risk stage II patients who responded the worst to adjuvant chemotherapy. Finally, a comparative analysis with previously reported Consensus Molecular Subgroup (CMS), high-risk patients classified by the PI revealed a distinct molecular property similar to CMS4, associated with a poor prognosis. This novel PI predictor based on an eleven gene signature likely represents a surrogate diagnostic tool for identifying high-risk CRC patients and for predicting the worst responding patients for adjuvant chemotherapy.

<p>Gene Expression Along with Genomic Copy Number Variation and Mutational Analysis Were Used to Develop a 9-Gene Signature for Estimating Prognosis of COAD</p>

“…In order to validate the superiority of our model, we found two published prognostic signature of colorectal cancer to make comparison, such as Zuo 21 and Kim. 22 To make it comparable, we used the corresponding genes in these two signatures. The risk score of each sample in TCGA was calculated using the same method, and the ROC and KM curve of each signature was evaluated.…”

Characterization of the Survival Influential Genes in Carcinogenesis

“…Next, to assess the association between the identified SIGs and cancer, we complied a cancer-associated gene list from three datasets: (1) 688 cancer genes from the COSMIC release (v85) [ 51 ]; (2) 550 cancer essential genes screened from the CRISPR system in human cancer cell lines [ 3 ]; and (3) 769 cancer genes from the cancer dependency map [ 4 ]. Additionally, we collected a small but highly confident harmful gene set from the literature [ 52 , 53 , 54 , 55 , 56 , 57 ]. We then performed enrichment analysis using Fisher’s exact test to evaluate the association between SIGs and cancer.…”

Natural podophyllotoxin analog 4DPG attenuates EMT and colorectal cancer progression via activation of checkpoint kinase 2

“…Survival rates of patients with CRC have improved in the past few years, probably due to earlier diagnosis and improved treatment of this disease. In spite of this, following potentially curative surgery,~30% of patients eventually develop local tumor recurrence or distant metastasis, resulting in an overall poor prognosis 3,4 . Such patients usually receive chemotherapy in combination with targeted monoclonal antibody therapy yielding response rates of, at best, 50% 3,5 .…”

“…In spite of this, following potentially curative surgery,~30% of patients eventually develop local tumor recurrence or distant metastasis, resulting in an overall poor prognosis 3,4 . Such patients usually receive chemotherapy in combination with targeted monoclonal antibody therapy yielding response rates of, at best, 50% 3,5 . 5-Fluorouracil (5-FU) is a pyrimidine analog chemotherapeutic drug currently being used in clinical practice since the 1950s as a first-line treatment option for CRC 6,7 .…”