A three-mRNA status risk score has greater predictive ability compared with a lncRNA-based risk score for predicting
Wenxia Zhang1, Qiang Fu2, Kanyu Yao3
1Department of Hepatobiliary Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010050, P.R. China.
Insights
A new three-messenger RNA (mRNA) risk score accurately predicts survival in hepatocellular carcinoma (HCC) patients. This mRNA-based score shows greater prognostic value than long non-coding RNA scores for HCC mortality prediction.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally.
- Accurate prognostic tools are crucial for effective patient management and risk stratification in HCC.
Purpose of the Study:
- To develop and validate a robust RNA-based risk score for predicting survival in hepatocellular carcinoma (HCC) patients.
- To compare the prognostic performance of mRNA-based and long non-coding RNA (lncRNA)-based risk scores.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) dataset to identify differentially expressed mRNAs and lncRNAs in HCC.
- Employed LASSO Cox proportional-hazards (Cox-PH) models to select prognostic RNAs.
- Generated and validated mRNA and lncRNA expression and status risk scores using TCGA and independent datasets.
Main Results:
- Identified significant differentially expressed mRNAs and lncRNAs between HCC and normal samples.
- Developed a three-mRNA signature and a five-lncRNA signature using the LASSO Cox-PH model.
- The three-mRNA status risk score demonstrated superior accuracy in predicting HCC patient mortality compared to other developed risk scores, including the lncRNA-based score.
Conclusions:
- A three-mRNA status risk score, utilizing hepatitis A virus cellular receptor 1, MYCN proto-oncogene BHLH transcription factor, and stratifin, offers a valuable and robust tool for HCC risk stratification.
- This mRNA-based risk score exhibits enhanced prognostic value over lncRNA-based scores for predicting HCC patient outcomes.
Abstract:
Hepatocellular carcinoma (HCC) represents the fifth most common cause of cancer-associated mortality in men, and the seventh in women, worldwide. The aim of the present study was to identify a reliable and robust RNA-based risk score for the survival prediction of patients with hepatocellular carcinoma (HCC). Gene expression data from HCC and healthy control samples were obtained from The Cancer Genome Atlas to screen differentially expressed mRNAs and long non-coding RNAs (lncRNAs). Univariate and multivariate Cox proportional-hazards regression models and the LASSO algorithm for the Cox proportional-hazards model (LASSO Cox-PH model) were used to identify the prognostic mRNAs and lncRNAs among differentially expressed mRNAs (DEMs) and differentially expressed lncRNAs (DELs), respectively. Prognostic risk scores were generated based on the expression level or status of the prognostic lncRNAs and mRNAs, and the predictive abilities of these RNAs in TCGA and validation datasets were compared. Functional enrichment analyses were also performed. The results revealed a total of 154 downregulated and 625 upregulated mRNAs and 18 upregulated lncRNAs between tumor and control samples in TCGA dataset. A three-mRNA and a five-lncRNA expression signatures were identified using the LASSO Cox-PH model. Three-mRNA and five-lncRNA expression and status risk scores were generated. Using likelihood ratio P-values and area under the curve values from TCGA and the validation datasets, the three-mRNA status risk score was more accurate compared with the other risk scores in predicting the mortality of patients with HCC. The three identified mRNAs, including hepatitis A virus cellular receptor 1, MYCN proto-oncogene BHLH transcription factor and stratifin, were associated with the cell cycle and oocyte maturation pathways. Therefore, a three-mRNA status risk score may be valuable and robust for risk stratification of patients with HCC. The three-mRNA status risk score exhibited greater prognostic value compared with the lncRNA-based risk score.
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