Currently, the identification of novel potential serum biomarkers for the detection of HCC remains a vital goal, particularly for the diagnosis of early-stage HCC. Nevertheless, only a few biomarker candidates have been translated to clinical applications due to the limited study cohorts or diagnostic performance. For instance, so far, there is still only AFP as the most commonly used biomarker for HCC patients, despite its unsatisfactory sensitivity and specificity [7]. Several HCC-related lncRNAs can be present in the body fluid, as is the case lncRNAs UCA1, WRAP53, PVT1, ATB and uc002mbe.2 [17, 21–23]. The representative lncRNA HULC is detectable in blood sample and can be easily quantified by conventional qPCR [24]. These findings have suggested a non-invasive approach for HCC diagnosis through circulating lncRNA measurement. Our study is the first to examine the potential diagnostic utility of serum SCARNA10 in HCC patients.
As previously researches, a large number of lncRNAs are aberrantly expressed in HCC compared with normal liver tissue, which is useful to distinguish HCC patients from healthy cohorts [25]. However, some of those lncRNAs are also shown abbrrant expression patterns in other cancer types or non-cancerous situations such as cirrhosis or liver injury, resulting in reduced reliability. Thus, lncRNAs combined with other molecules, especially known HCC biomarker AFP, is more likely to be a desirable HCC diagnosis method instead of evaluating lncRNAs alone. For example, the combination of two lncRNAs UCA1 and WRAP53 with AFP achieves sensitivity up to 100% [21]. Similarly, the combination of another two lncRNAs PVT1 and uc002mbe.2 with AFP have been also shown to perform much better than AFP alone in HCC diagnosis [22]. Besides AFP, other molecules including miRNAs or mRNAs can also predict HCC in combination with lncRNAs [26]. In this study, for the first time, we found that the levels of SCARNA10 in HCC patients were significantly higher than that in BLD patients and healthy controls. Moreover, the SCARNA10 levels were not notable divergence between BLD patients and HC. These demonstrated that serum SCARNA10 levels can clearly distinguish benign and malignant liver tumors. In addition, the ROC analysis suggested that the AUCs of the combined SCARNA10 and AFP were greater than themself alone in distinguishing HCC from BLD and HCC from HC. The sensitivity of the two combined markers were also increased. Finally, in AFP-negative HCC, SCARNA10 also showed a significant ability with higher sensitivity and specificity. All these findings indicated that SCARNA10 can serve as a potential diagnostic biomarker for HCC.
HBV infection is the major risk factor for HCC development. Worldwide, >50% of HCC cases are associated with HBV infection [2, 27]. Several lines of evidence have supported the direct involvement of HBV in driving hepatocarcinogenesis. For example, the HBV genome can integrate into the human genome, contributing to genomic instability and generation of oncogenic chimeric transcripts [28]. HBV protein X (HBx) is highly carcinogenic, and 90% of HBx transgenic mice develop HCC [29]. HCV infection is a major cause of cirrhosis and consequently HCC [30]. The molecular mechanisms underlying HCV-induced HCC development might differ from those associated with HBV infection. HCV could promote HCC formation by upregulating host miRNAs and deregulating cellular signalling pathways [31, 32]. In this study, we found that serum SCARNA10 levels in HCC patients with HBV or HCV infection were significantly higher than those without infection controls, and in HCC patients with liver cirrhosis were also increased. These results demonstrated that SCARNA10 may play a role in HCC by regulating a common pathway in HBV or HCV. All these provide ideas for further research on the function and mechanism of SCARNA10 in HCC in the future.
In conclusion, we found the serum SCARNA10 level was increased in HCC patients, and associated with some clinicopathologic features, including tumor size, differentiation degrees, stage, vascular invasion, metastasis and complications. The combined detection of SCARNA10 and AFP significantly imporved the diagnostic sensitivity of HCC. However, the roles of SCARNA10 in HCC need to be elucidated in more detail. In future study, we will further research the definite function and mechnism of SCARNA10 in liver carcinogenesis.