Risk score based on ten lncRNA-mRNA expression predicts the survival of stage II-III colorectal carcinoma

Abstract

The prognosis of colorectal carcinoma (CRC) is unstable in the stage II-III patients. Patients with early stage II CRC have a relative poor prognosis while other stage III CRC patients have a better prognosis. In our work, by utilizing the expression of lncRNAs and mRNAs measured by microarray (GSE39582), we constructed a risk score staging system with Cox multivariate regression model to predict the outcome of grade II-III CRC patients. Ten genes including two lncRNAs and eight mRNAs were used to estimate the survival of stage II-III CRC patients. The patients with high risk scores have poorer survival rate those with low risk scores, significantly. These results were further validated in another three independent datasets (GSE37892, GSE33113, and GSE17536). The relationship between clinical information and were evaluated, and the risk score is independent from the other clinical information and performs better in evaluating the survival of stage II-III CRC patients. Moreover, the correlation between chemotherapy was also evaluated, and we found that both patients with or without chemotherapy have a poor survival in high risk group. Gene Set Enrichment Analysis were used to find the difference between high-risk and low-risk groups, and pathways including cell adhesion and focal adhesion were significantly enriched, suggesting that the risk score reflects the status of cell-cell physical interaction. In summary, we constructed a risk staging model for grade II-III CRC, which is independent from and performs better than clinical information.

Fig 1. Genes selected for risk score model.

The -log 10 transformed p value for Cox univariate regression (A) and multivariate coefficient (B) for each gene was shown.

Fig 2. The performance of risk score on training dataset.

The overall (A) and recurrence free (B) survival difference between risk-high and risk-low were shown. The detailed survival information and gene expression pattern of candidate genes were different in risk-low and risk high (C) group (Top panel, risk score, middle panel, survival status, bottom panel, candidate gene expression profile). The risk score performs better than other clinical information in predicting the 3-year survival.

Fig 3. The performance of risk score in other two independent cohorts.

The survival difference of risk-high and risk-low group in another two independent datasets, GSE33113 (A) and GSE37892 (B), resembles the profile of the training datasets.

Fig 4. The correlation between risk score and other clinical information and its performance in predicting survival time.

The risk score is independent of other clinical information (A), and contributed more in predicting 3-year survival (B, 3-year survival nomogram). Risk score is effective for patients underwent chemotherapy or not.

Fig 5. The significantly altered KEGG pathways in the risk-high group.

Among these pathways (A), focal adhesion (B) and cell adhesion molecular cams (C) was noted.