| BackgroundHepatocellular carcinoma (HCC) is a highly heterogeneous malignancy which is seriously jeopardizing the health of Chinese people. The carcinogenic process of HCC involves synergetic effects of multiple genes and environmental factors, requires various pathologic stages and engages a number of molecular events. Although the information obtained from limited studies on HCC-related noncoding RNAs (ncRNAs) in recent years can be suggestive, they have not yet reached the level of large-scale transcriptome research; particularly, there are currently few reports on the differential expression of small ncRNA and mRNA-like ncRNA in HCC. With microarray analysis of novel small ncRNAs and mRNA-like ncRNAs in HCCs, this study will be complementary to high throughput researches on HCC-related ncRNAs. It will for the first time establish a high throughput model of hepatocyte-specific ncRNA sequencing and pilot the related field.On the other hand, HCCs in China mainly develop on the basis of chronic hepatitis B and cirrhosis. Although either the absolute number or the relative ratio of hepatitis B in China is among the highest in the world, there are few persuasive reports of large-scale prospective cohort studies on the relationship of hepatitis B and HCC, and sufficient evidence from long-term follow-ups which directly focus on the clinical consequences of chronic hepatitis B is still lacking, as it may take years for them to develop.ObjectiveTo identify novel HCC-specific noncoding genes.To identify novel biomarkers for early diagnosis of HCC.To investigate the carcinogenic mechanism of HCC, to facilitate the classification of HCC genes, choice of treatment regime, and prediction of prognosis.To investigate the relationship of hepatitis B virus (HBV) infection status and HCC development.MethodsIn Part I, large-scale ncRNA databases were established by in silico computing. A specimen collection which includes various differentiated HCCs and their matched noncancerous tissues were established, patients'clinicopathological characteristics were systematically recorded, and a liver-specific ncRNA library was constructed. By hybridizing with gene chips containing novelly identified small ncRNAs and mRNA-like ncRNAs, microarray analysis was applied to search for target genes that differentially expressed in HCC, which were then verified by RT-PCR and Northern blot. A HCC-related ncRN A database will be established by integrating results of this study with available data of other ncRNA chips.In Part II, the medical records of patients who were admitted into Peking Union Medical College Hospital (PUMCH) and Youan Hospital, and underwent hepatectomy followed with a pathologically confirmed diagnosis of HBV-related HCC, and the results of HBV-related tests in PUMCH Health Checkup Center were retrospectively analyzed.ResultsIn Partâ… , four large-scale ncRNA databases were established, i.e. NONCODE, antiCODE, HPtaa, and HPtam.30 differentially expressed novel ncRNAs were identified in HCC specimens.6 of them were selected and verified by Northern blot.In Partâ…¡, a total of 371 patients with HBV-related HCC were enrolled, male/female: 317/54; median age:53 yrs; median ALT:41 U/L,48.5% were with a normal ALT level at HCC diagonosis; patients who were HBsAg carriers, HBsAg-positive/HBeAg-positive, HBsAg-positive/HBeAg-negative, and HBsAg-seronegative were 87.6%,15.9%,65.5% and 12.4% respectively. Compared with the data from regular health checkups, the ratio of HBeAg-positive patients with HBV-related HCC to HBeAg-negative ones was not significantly different (P=0.1460). HBV DNA levels were determined in a total of 139 patients with HBV-related HCC. Among them, the rates of HBV DNA<103,103-104, and>104 copies/mL were 51.1%,8.6% and 40.3% respectively. According to the data from regular health checkups, HBsAg carrier rate was 2.74% (3,548/129,568). The ratio of HBeAg-positive to HBeAg-negative patients in company-organized participants was significantly different from that in individual ones (136/810 vs 283/1,333,P=0.0383).ConclusionsPartâ… reveals that there are a large number of novel ncRNAs which specifically express in HCCs, suggesting the promise of these ncRNAs in HCC-related field. It is warranted to further investigate their functions, to analyze their relationship with clinicopathological features for the diagnosis, treatment and classification of HCC, to construct the transcription modulation network in HCC to understand its carcinogenic mechanisms, and to explore novel target genes to prevent HCC development.Partâ…¡indicates that the risk of HCC development in HBsAg-positive, HBeAg-negative patients seems to be similar to that in HBsAg-positive, HBeAg-positive ones; patients with a HBV DNA level<103 copies/mL are still at a higher risk of HCC. At present, collecting data from major medical institutes and disease control centers and conducting large-scale clinical investigations are warranted to provide supports for the primary, secondary and third preventions against hepatitis B. |
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