A three‑mRNA status risk score has greater predictive ability compared with a lncRNA‑based risk score for predicting prognosis in patients with hepatocellular carcinoma

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.

Local and systemic autoimmune manifestations linked to hepatitis A infection

“…Nevertheless, the GAL-9/ TIM-3 pathway downregulates normal immunity and facilitates the survival of HCC malignant cells, thus consisting a potential target of future treatments (47). Moreover, human hepatitis A virus cellular receptor (HAVCR)-1, known as T-cell immunoglobulin and a mucin domain containing molecule 1 (TIM-1), beyond its role in autoimmune disorders (48,49), is implicated in oncogenic linked actions, such as cell proliferation, differentiation or dissemination events, thereby consisting an additional target for cancer therapy (50); HAVCR-1 may be involved in the pathophysiology of certain malignancies including HCC (51,52); HAVCR-1 overexpression in cancer is linked with disruption of tight junctions and malignant metastasis (53); and loss of cohesion of the tight junction structure can result in invasion and ultimately in metastasis of malignant cells (54). However, the above-mentioned considerations warrant future research to elucidate in depth their hypo-auto-inflammatory disorder characterized by fever, maculopapular rash on the trunk and legs, generalized arthralgia, severe neutrophilic leukocytosis, and hyperferritinemia, effectively controlled by steroids (62).…”