Identification and Analysis of the Blood lncRNA Signature for Liver Cirrhosis and Hepatocellular Carcinoma

Abstract

As one of the most common malignant tumors, hepatocellular carcinoma (HCC) is the fifth major cause of cancer-associated mortality worldwide. In 90% of cases, HCC develops in the context of liver cirrhosis and chronic hepatitis B virus (HBV) infection is an important etiology for cirrhosis and HCC, accounting for 53% of all HCC cases. To understand the underlying mechanisms of the dynamic chain reactions from normal to HBV infection, from HBV infection to liver cirrhosis, from liver cirrhosis to HCC, we analyzed the blood lncRNA expression profiles from 38 healthy control samples, 45 chronic hepatitis B patients, 46 liver cirrhosis patients, and 46 HCC patients. Advanced machine-learning methods including Monte Carlo feature selection, incremental feature selection (IFS), and support vector machine (SVM) were applied to discover the signature associated with HCC progression and construct the prediction model. One hundred seventy-one key HCC progression-associated lncRNAs were identified and their overall accuracy was 0.823 as evaluated with leave-one-out cross validation (LOOCV). The accuracies of the lncRNA signature for healthy control, chronic hepatitis B, liver cirrhosis, and HCC were 0.895, 0.711, 0.870, and 0.826, respectively. The 171-lncRNA signature is not only useful for early detection and intervention of HCC, but also helpful for understanding the multistage tumorigenic processes of HCC.

Role of three-dimensional printing and artificial intelligence in the management of hepatocellular carcinoma: Challenges and opportunities

“…Current efforts include predicting HCC development in patients with chronic HBV infection[ 48 ] and chronic HCV infection[ 51 - 54 ]. Other studies focusing on prevention have developed AI/ML models employing genetic and epigenetic markers such as long-coding RNAs to screen for HCC[ 47 , 49 , 50 ]. These models demonstrate how AI could facilitate tailoring individualized follow-up schedules and identifying patients at a greater need to achieve a SVR.…”

“…Other studies have employed data from gene sequencing and expression patterns. Specifically, in a study, data from circulating long non-coding RNAs were employed to develop an AI/ML model that isolated distinctive signatures of expression of 171 different long non-coding RNAs that distinguish the healthy control group from patients with chronic HBV, liver cirrhosis, and HCC[ 49 ]. Another study developed four different models that used data from reverse transcriptase gene sequencing to predict the patients with HBV who would develop HCC[ 50 ].…”

The multifaceted perspectives on the regulation of lncRNAs in hepatocellular carcinoma ferroptosis: from bench-to-bedside

“…LncRNAs could be detectable in the bloodstream of HCC patients [ 143 ]. Moreover, lcnRNAs expression are significantly dysregulated in the blood of HCC patients, suggesting a novel strategy for HCC diagnosis [ 143 ].…”

“…LncRNAs could be detectable in the bloodstream of HCC patients [ 143 ]. Moreover, lcnRNAs expression are significantly dysregulated in the blood of HCC patients, suggesting a novel strategy for HCC diagnosis [ 143 ]. Studies have revealed that plasma level of HULC and NEAT1 are markedly elevated in HCC patients [ 144 , 145 ], serving as significant predictors of HCC tumor growth and metastasis, which hold promise as non-invasive biomarkers for diagnosing hepatoma, and their diagnostic accuracy may be enhanced when combined with AFP [ 145 – 147 ].…”

Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma

“…In addition to mutations that directly affect the integrity of p53, genes involved in the negative feedback loop also contribute to disease development. In principle, the 309T > G polymorphism (SNP 309, rs2279744), located in the intronic p53-responsive promoter of MDM2 , has the effect of increasing Mdm2 protein levels and is associated with the early onset of HCC in patients with chronic HCV infection [ 62 , 136 ]. Recently, KRAB-type zinc-finger protein (ZNF498) was found to be upregulated and therefore suppress apoptosis and ferroptosis by attenuating p53 Ser46 phosphorylation in hepatocellular carcinogenesis [ 51 ].…”