Long noncoding RNA MyD88 functions as a promising diagnostic biomarker in hepatocellular carcinoma

Abstract

BackgroundHepatocellular carcinoma (HCC) is one of the most frequent malignancies. Alpha-fetoprotein (AFP) has some limitations in diagnosing early HCC. Recently, long noncoding RNAs (lncRNAs) showed great potential as tumor diagnostic biomarkers, and lnc-MyD88 was previously identified as a carcinogen in HCC. Here, we explored its diagnostic value as a plasma biomarker.Materials and methodsQuantitative real-time PCR was adopted to detect lnc-MyD88 expression in plasma samples of 98 HCC patients, 52 liver cirrhosis (LC) patients, and 105 healthy people. The correlation between lnc-MyD88 and clinicopathological factors was analyzed through chi-square test. The receiver operating characteristic (ROC) curve was used to analyze the sensitivity, specificity, Youden index, and area under the curve (AUC) of lnc-MyD88 and AFP alone and in combination for the diagnosis of HCC. The relationship between MyD88 and immune infiltration was analyzed by single sample gene set enrichment analysis (ssGSEA) algorithm.ResultsLnc-MyD88 was highly expressed in plasma samples of HCC and hepatitis B virus (HBV)-associated HCC patients. Lnc-MyD88 had better diagnostic value than AFP in HCC patients using healthy people or LC patients as control (healthy people, AUC: 0.776 vs. 0.725; LC patients, AUC: 0.753 vs. 0.727). The multivariate analysis showed that lnc-MyD88 had great diagnostic value for distinguishing HCC from LC and healthy people. Lnc-MyD88 had no correlation with AFP. Lnc-MyD88 and AFP were independent diagnostic factors for HBV-associated HCC. The AUC, sensitivity, and Youden index of the combined diagnosis of lnc-MyD88 and AFP combined were higher than those of lnc-MyD88 and AFP alone. The ROC curve of lnc-MyD88 for the diagnosis of AFP-negative HCC was plotted with a sensitivity of 80.95%, a specificity of 79.59%, and an AUC value of 0.812 using healthy people as control. The ROC curve also presented its great diagnostic value using LC patients as control (sensitivity: 76.19%, specificity: 69.05%, AUC value: 0.769). Lnc-MyD88 expression was correlated with microvascular invasion in HBV-associated HCC patients. MyD88 was positively correlated with infiltrating immune cells and immune-related genes.ConclusionThe high expression of plasma lnc-MyD88 in HCC is distinct and could be utilized as a promising diagnostic biomarker. Lnc-MyD88 had great diagnostic value for HBV-associated HCC and AFP-negative HCC, and it had higher efficacy in combination with AFP.