In this present study, we analyzed the expression of two miRNAs, miR-143 and miR-215, in the serum among the patients with healthy controls, chronic hepatitis and HCC patients. We found that miR-143 and miR-215 expression was up-regulated in the serum samples from patients with chronic hepatitis and HCC compared with the controls. In addition, we conduct ROC analyses to detect the potential application of miR-143 and miR-215 in the diagnoses of chronic hepatitis and HCC. Our results showed that miR-143 and miR-215 might be potential biomarkers for both hepatitis and HCC. Our current data indicated that serum miR-143 and miR-215 expression might be further evaluated as novel noninvasive diagnostic biomarkers for HCC.
A lot of previous studies reported that miRNA expression is aberrant through HCC development; however, most of these studies focused on the expression of miRNAs in HCC tissues and cell lines. For example, a previous study focused on microRNA expression profiles in human hepatitis B virus-related HCC. Based on the data of 11 pairs of HCC and matched non-tumorous tissues from 11 HBV infection patients, miR-96, miR-183, and miR-196a were up-regulated significantly, while let-7c and miR-138 were down-regulated
. Xiao et al. conduct a follow-up study and the results revealed that miR-200a was frequently downregulated in HCC. In addition, multivariate analysis confirmed that miR-200a was significantly associated with the overall survival of HCC patients
. In an other study, Yu et al. found that miR-424 was down-regulated in HCC cell lines compared a normal hepatocytes and in vitro studies showed that miR-424 is effective in the neoplasty of HCC
Although tissue miRNAs can provide an accurate diagnosis for various types of cancer, the difficulty in collecting tissue samples limits its application for the detection of cancer biomarkers. Acquiring tissue samples is an invasive procedure and depends on surgical sections after initial clinical classification
. The search for noninvasive tools for the diagnosis of cancer has long been a goal of many researchers, and much of the interest has been on the circulation of nucleic acids in plasma and serum. Compared with DNA and mRNA, circulating miRNAs show remarkable stability after prolonged incubation at room temperature and/or multiple freezing-thawing processes. However, the protective mechanism of circulating miRNAs is still unknown. Some investigators reported that circulating miRNAs were in the form of argonaute 2 (Ago2)-miRNA complexes that could avoid RNase digestion
Nowadays, there are increasing studies being conducted to identify specific circulating miRNAs in the diagnosis of HCC. Giray et al. conducted a study to investigate the potential of certain serum/plasma miRNAs as novel non-invasive biomarkers for early diagnosis of HBV related HCC. Through comprehensive tests of 94 plasma samples (28 control and 66 patient plasma samples), a series of related miRNAs were reported in the study and the expression of miR-223 was the most significant. Microvesicles (MVs) packaged with miRNAs were reported to be released mainly from tumor cells. Sun et al. conduct expression profiles to detect the differently expressed miRNAs. The results showed that a total of 242 aberrantly expressed miRNAs were identified in HCC-MVs compared with CHB-MVs and the control. Among them, 115 miRNAs were up-expressed with up to 31 fold difference (miR-671-5p) and 127 were down-expressed with up to 0.041 fold difference (miR-432) in HCC
. A potential correlation was also evaluated between miR-101 expression and the clinicopathological features and prognosis of HCC patients. It was reported that miR-101 was down-regulated in HBV-related HCC tissues compared with adjacent noncancerous tissues. Furthermore, the miR-101 levels in these tissues from HCC patients were significantly lower than those in tissues from control subjects
In this present study, we focus on the diagnostic value of miR-143 and miR-215 for the chronic hepatitis and HCC. Previous reports have shown that the expression of miR-143 is extremely down-regulated in colorectal cancer, lung, bladder, and gastric cancers
[29–31]. While it is reported the expression of miR-143 is up-regulated in pancreatic stellate cells cancer and esophageal cancer
[32, 33]. There are few reports about the relationship between miR-143 expression and the diagnosis of HCC. Up to now, only one study reported the association between miR-143 and HCC. Zhang et al. reported that the levels of miRNA-143 (miR-143) are dramatically increased in metastatic HBV-HCC of both p21-HBx transgenic mice and HCC patients. Advanced study showed that up-regulation of miR-143 expression promotes cancer cell invasion/migration and tumor metastasis by repression of FNDC3B expression
. The association between miR-215 and cancer were also reported. Senanayake et al. reported that miR-215 had a significantly lower expression in nephroblastomas regardless of the subtype compared with mature kidney measured by quantitative real-time-PCR
. White et al. performed experimental and bioinformatic analyses to explore the involvement of miR-215 in renal cell carcinoma progression and metastasis. In vitro study showed that miR-215 might contribute to kidney cancer metastasis through different biological processes
. In a previous study, miR-215 was reported to be up-regulated in HCC cancer cases
. Ishida et al. reported that using miRNA array analysis, miR-192/miR-215, miR-194, miR-320, and miR-491 were identified as being altered by HCV infection. Among them, miR-192/miR-215 and miR-491 were capable of enhancing replication of the HCV replicon as well as HCV itself
. To our best knowledge, this is the first study that reports the association between miR-143/miR-215 and HCC. More related studies are wanted to investigate to clinical application and detailed mechanisms.
Recent years, more and more studies raised diagnostic and prognostic application of miRNAs in different diseases, including cancer. Their application to body specimens from blood to tissues has been helpful for appreciating their use in the clinical context
. Our results showed that serum miR-143 and miR-215 were commonly up-regulated in chronic hepatitis and HCC patients, suggesting miR-143 and miR-215 may be new potential diagnostic biomarkers and targets of chronic hepatitis and HCC. However, as a case–control study without a long-time follow-up, the prognostic effect of the two miRNAs could not be detected in this study. A follow-up of this cohort would be reportedand more advanced analyses would be conducted.