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Background Simple hepatic cysts are relatively common in adults, and mostly appear as asymptomatic incidental radiologic findings. Occasionally, a large cyst will cause symptoms. Elevations in the serum biomarkers protein induced by vitamin K absence (PIVKA)-II, cancer antigen (CA) 12-5, and CA19-9 are often associated with malignant tumors in the liver or bile ducts. This is the first report to describe a case of hepatic cyst with elevated levels of PIVKA-II and CA12-5. Case summary An 84-year-old Chinese woman was admitted with gradual abdominal distension. Her symptoms started 1 year ago, and she had poor appetite and a weight loss of 5 kg within the past 2 wk. She denied any symptoms associated with abdominal pain, fever and chills, nausea and vomiting, etc. The abdomen was enlarged, more in the right upper quadrant, without tenderness. Laboratory examination showed significantly increased serum levels of PIVKA-II, CA12-5, and CA19-9. A computed tomography scan revealed multiple round cysts in the liver with clear boundaries. The largest cyst was 20.1 cm × 12.2 cm × 19.6 cm in size, located in the right lobe of the liver with mild dilatation of the intrahepatic bile duct, but there was no contrast enhancement. Percutaneous drainage on the largest hepatic cyst and polycinnamol sclerosing agent injection into the cyst cavity were performed. After treatment, the patient's symptoms relieved and the elevated serum tumor makers reduced to the normal levels dramatically. Conclusion The present report identifies an unusual case of a giant hepatic cyst with marked elevation of serum tumor marker levels of PIVKA-II, CA12-5, and CA19-9. After treatment, these three serum markers dramatically decreased to normal levels. The mechanisms for the elevation of these tumor markers may be as follows: (1) A giant hepatic cyst compresses the liver, causing injury to the hepatocytes, which may lead to secretion of a large amount of PIVKA-II; and (2) Some tumor-associated antigens, such as carcinoembryonic antigen, CA19-9, CA12-5, and CA15-3, are expressed on inflammatory cells.

Background The decline of a long non-coding RNA (lncRNA) DIO3OS was implicated in a plethora of cancers, while the relevance in hepatocellular carcinoma (HCC) has not been mentioned. Accordingly, we set to determine the functional role of DIO3OS and the molecular mechanism in HCC progression. Materials and methods The differentially expressed lncRNAs, mRNAs, and microRNAs (miRNAs) were obtained through the datasets GSE101728 and GES57555. Afterwards, DIO3OS was enhanced in HCC cells to examine the behavior changes. Subcellular localization of DIO3OS was determined through website prediction and experimental validation. The expression of Hedgehog (Hh) signaling pathway-related genes was detected. The effects of DIO3OS overexpression on tumor growth were evaluated as well. Results DIO3OS was lower in HCC tissues and cells, while upregulation of DIO3OS repressed malignant biological behavior both in vitro and in vivo. DIO3OS, localized in the cytoplasm, inhibited the occurrence of HCC by disrupting the Hh pathway by sponging miR-328 to mediate Hh interacting protein (Hhip). Conclusion All in all, the obtained data suggested that DIO3OS interacted with Hhip-dependent Hh signaling pathway to inhibit HCC progression through binding to miR-328, which may be a potent therapeutic target for HCC.

Aim There are no existing biomarkers that demonstrate very reliable performance in the diagnosis of hepatocellular carcinoma (HCC), especially in the early stage. Studies have shown that numerous aberrantly expressed circulating microRNAs (miRNAs) can be used as a diagnostic tool for HCC; however, these studies have produced inconsistent results. Methods We performed a meta-analysis to summarize the diagnostic accuracy of circulating miRNAs, alpha-fetoprotein (AFP), and AFP combined with miRNAs in differentiating HCC patients from non-HCC controls, healthy controls and chronic liver disease controls. We also evaluated the diagnostic accuracy of circulating miRNAs for early-stage HCC. Furthermore, we systematically reviewed the diagnostic effectiveness of single miRNAs and individual miRNA panels. Results Circulating miRNAs showed good diagnostic performance. Compared with single miRNAs, the diagnostic accuracy of miRNA panels was clearly better. The combination of AFP and miRNAs improved the diagnostic accuracy compared with the use of miRNAs or AFP alone. For early-stage HCC patients, circulating miRNAs exhibited relatively satisfactory diagnostic accuracy. Conclusions Circulating miRNAs can be used as an early diagnostic marker of HCC. The combination of miRNAs and AFP has great potential as a novel strategy for the diagnosis of HCC.

Current advances of molecular-targeting therapies for hepatocellular carcinoma (HCC) have improved the overall survival significantly, whereas the results still remain unsatisfied. Recently, much attention has been focused on organelles, such as the mitochondria, to reveal novel strategies to control the cancers. The mitochondria are vital organelles which supply energy and maintain metabolism in most of the eukaryotic cells. They not only execute critical bioenergetic and biosynthetic functions but also regulate ROS homeostasis and apoptosis. Existing in a dynamic equilibrium state, mitochondria constantly undergo the fission and fusion processes in normal situation. Increasing evidences have showed that mitochondrial fission is highly related to the diseases and cancers. Distinctive works have proved the significant effects of mitochondrial fission on HCC behaviors and the crosstalks with other molecular pathways. Here, we provide an overview of the mitochondrial fission and the link with HCC, emphasizing on the underlying molecular pathways and several novel materials that modulate HCC behaviors.

Yanshuo Ye,1 Yuan An,1 Min Wang,2 Hongyu Liu,1 Lianyue Guan,1 Zhanpeng Wang,1 Wei Li1 1Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Pathology, Jilin Provincial Cancer Hospital, Changchun 130012, People’s Republic of ChinaCorrespondence: Wei LiDepartment of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of ChinaEmail weili888@jlu.edu.cnBackground: Carboxypeptidase X, M14 family member 2 (CPXM2) has been reported to be involved with several human malignancies. However, the impact of CPXM2 on human hepatocellular carcinoma (HCC) tumorigenesis has not been studied.Materials and Methods: Using immunohistochemistry, the detailed CPXM2 expression patterns were examined in HCC cell lines and tissues. Additionally, a hepatic stellate cell line overexpressing CPXM2 and an HCC CPXM2-knockdown cell line were established by lipofection of an expression plasmid or short hairpin RNA, respectively. The transfection efficiencies were confirmed by reverse transcription-quantitative PCR, Western blotting and immunofluorescence. Moreover, Western blotting was conducted to determine the phosphorylation levels of the tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription 3 (Stat1) pathway. Furthermore, gp130-specific hairpin RNA was used to knockdown gp130 expression in hepatic stellate cells overexpressing CPXM2. The malignant phenotype of cultured HCC cells was assessed by a Cell Counting Kit-8 (CCK8) assay, plate cloning assay, Matrigel invasion assay and wound-healing assay in vitro.Results: It was demonstrated that CPXM2 was upregulated in HCC, and its upregulation predicted a poor prognosis. Besides, the upregulation of CPXM2 markedly enhanced the metastatic potential of HCC via the gp130/JAK2/Stat1 signaling pathway in vitro.Conclusion: In summary, this evidence suggests a positive role for CPXM2 in HCC progression via modulation of the gp130/JAK2/Stat1 signaling pathway in HCC.Keywords: carboxypeptidase XM14 family member 2, hepatocellular carcinoma, metastasis

Accumulating evidence has indicated that oxidative stress (OS) is associated with the development of hepatocellular carcinoma (HCC). However, the mechanisms remain largely unknown. Normally, OS occurs when the body receives any danger signal—from either an internal or external source—and further induces DNA oxidative damage and abnormal protein expression, placing the body into a state of vulnerability to the development of various diseases such as cancer. There are many factors involved in liver carcinogenesis, including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, alcohol abuse, and nonalcoholic fatty liver disease (NAFLD). The relationship between OS and HCC has recently been attracting increasing attention. Therefore, elucidation of the impact of OS on the development of liver carcinogenesis is very important for the prevention and treatment of liver cancer. This review focuses mainly on the relationship between OS and the development of HCC from the perspective of cellular and molecular mechanisms and the etiology and therapeutic targets of HCC.

γδ T cells are unique population of T cells in which their function still remain unclear. We have demonstrated that γδ T cell mainly located in the liver in mice. Our previous data based on liver transplantation model suggests that γδT cells are involved in the processes of liver transplant tolerance and rejection, and may play a role in the induction of liver graft rejection. In contrast to Foxp3+ CD4+ CD25+ Treg, the majority of γδT cells were mainly located in the liver and did not express TCRαβ and NK receptors, but expressed moderate levels of PD-1 and PD-L1 molecules. It has recently been shown that γδT cells play an important role against tumors and infectious diseases. Methods In this study we employed mouse orthotopic hepatocellular carcinoma model, critically examine the role of γδ T cells in the liver and peripheral on liver cancer development. Results The ratio of CD3+ T cells were decreased, but γδ T cells were increased in the surrounding tissue of the tumor and the spleen. Anti-γδ T cells antibody plus IL-2 treatment to tumor barrier mice could further increase the γδ T cells in the liver and spleen and limited the growth of the tumor. Conclusion γδ T cell may plays an important role in immunologic defence against hepatocellular carcinoma. More studies underlying the mechanisms and interplay among liver immune cells are under investigation.