Immune-Related Gene Expression and Cytokine Secretion Is Reduced Among African American Colon Cancer Patients

Background. Colon cancer (CC) is a malignant tumor with a high incidence and poor prognosis. Accumulating evidence shows that the immune signature plays an important role in the tumorigenesis, progression, and prognosis of CC. Our study is aimed at establishing a novel robust immune-related gene pair signature for predicting the prognosis of CC. Methods. Gene expression profiles and corresponding clinical information are obtained from two public data sets: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO, GSE39582). We screened out immune-related gene pairs (IRGPs) associated with prognosis in the discovery cohort. Lasso-Cox proportional hazard regression was used to develop the best prognostic signature model. According to this, the patients in the validation cohort were divided into high immune-risk group and low immune-risk group, and the prediction ability of the signature model was verified by survival analysis and independent prognostic analysis. Results. A total of 17 IRGPs composed of 26 IRGs were used to construct a prognostic-related risk scoring model. This model accurately predicted the prognosis of CC patients, and the patients in the high immune-risk group indicated poor prognosis in the discovery cohort and validation cohort. Besides, whether in univariate or multivariate analysis, the IRGP signature was an independent prognostic factor. T cell CD4 memory resting in the low-risk group was significantly higher than that in the high-risk group. Functional analysis showed that the biological processes of the low-risk group included “TCA cycle” and “RNA degradation,” while the high-risk group was enriched in the “CAMs” and “focal adhesion” pathways. Conclusion. We have successfully established a signature model composed of 17 IRGPs, which provides a novel idea to predict the prognosis of CC patients.

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A New Oxaliplatin Resistance-Related Gene Signature With Strong Predicting Ability in Colon Cancer Identified by Comprehensive Profiling

Frontiers in Oncology ◽

10.3389/fonc.2021.644956 ◽

2021 ◽

Vol 11 ◽

Author(s):

Qiu Lin ◽

Li Luo ◽

Hua Wang

Keyword(s):

Gene Expression ◽

Colon Cancer ◽

Cancer Patients ◽

Risk Score ◽

Cox Regression ◽

Differential Expression Analysis ◽

Gene Signature ◽

Single Individual ◽

Related Gene ◽

Specificity And Sensitivity

Numerous colon cancer cases are resistant to chemotherapy based on oxaliplatin and suffer from relapse. A number of survival- and prognosis-related biomarkers have been identified based on database mining for patients who develop drug resistance, but the single individual gene biomarker cannot attain high specificity and sensitivity in prognosis prediction. This work was conducted aiming to establish a new gene signature using oxaliplatin resistance-related genes to predict the prognosis for colon cancer. To this end, we downloaded gene expression profile data of cell lines that are resistant and not resistant to oxaliplatin from the Gene Expression Omnibus (GEO) database. Altogether, 495 oxaliplatin resistance-related genes were searched by weighted gene co-expression network analysis (WGCNA) and differential expression analysis. As suggested by functional analysis, the above genes were mostly enriched into cell adhesion and immune processes. Besides, a signature was built based on four oxaliplatin resistance-related genes selected from the training set to predict the overall survival (OS) by stepwise regression and least absolute shrinkage and selection operator (LASSO) Cox analysis. Relative to the low risk score group, the high risk score group had dismal OS (P < 0.0001). Moreover, the area under the curve (AUC) value regarding the 5-year OS was 0.72, indicating that the risk score was accurate in the prediction of OS for colon cancer patients (AUC >0.7). Additionally, multivariate Cox regression suggested that the signature constructed based on four oxaliplatin resistance-related genes predicted the prognosis for colon cancer cases [hazard ratio (HR), 2.77; 95% CI, 2.03–3.78; P < 0.001]. Finally, external test sets were utilized to further validate the stability and accuracy of oxaliplatin resistance-related gene signature for prognosis of colon cancer patients. To sum up, this study establishes a signature based on four oxaliplatin resistance-related genes for predicting the survival of colon cancer patients, which sheds more light on the mechanisms of oxaliplatin resistance and helps identify colon cancer cases with a dismal prognostic outcome.

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