Hepatocellular Tumors:Immunohistochemical Analyses for Classification and Prognostication

Following the classification of hepatocellular nodules by the International Working Party in 1995 and further elaboration by the International Consensus Group for Hepatocellular Neoplasia in 2009, entities under the spectrum of hepatocellular nodules have been better characterized. Research work hence has been done to answer questions such as distinguishing high-grade dysplastic nodules from early hepatocellular carcinoma (HCC), delineating the tumor cell origin of HCC, identifying its prognostic markers, and subtyping hepatocellular adenomas. As a result, a copious amount of data at immunohistochemical and molecular levels has emerged. A panel of immunohistochemical markers including glypican-3, heat shock protein 70 and glutamine synthetase has been found to be of use in the diagnosis of small, well differentiated hepatocellular tumors and particularly of HCC. The use of liver fatty acid binding protein (L-FABP), β-catenin, glutamine synthetase, serum amyloid protein and C-reactive protein is found to be helpful in the subtyping of hepatocellular adenomas. The role of tissue biomarkers for prognostication in HCC and the use of biomarkers in subclassifying HCC based on tumor cell origin are also discussed.

Viral integration detection strategies and a technical update on Virus-Clip

Oncovirus infection is crucial in human malignancies.Certain oncoviruses can lead to structural variations in the human genome known as viral genomic integration,which can contribute to tumorigenesis.Existing viral integration detection tools differ in their underlying algorithms pinpointing different aspects or features of viral integration phenomenon.We discuss about major procedures in performing viral integration detection.More importantly,we provide a technical update on Virus-Clip to facilitate its usage on the latest human genome builds(hg19 and hg38)and the adoption of multi-thread mode for faster initial read alignment.By comparing the execution of Virus-Clip using single-thread and multi-thread modes of read alignment on targeted-panel sequencing data of HBV-associated hepatocellular carcinoma patients,we demonstrate the marked improvement of multi-thread mode in terms of significantly reduced execution time,while there is negligible difference in memory usage.Taken together,with the current update of Virus-Clip,it will continue supporting the in silico detection of oncoviral integration for better understanding of various human malignancies.

Single cell analysis informing therapy response in hepatocellular carcinoma and intrahepatic cholangiocarcinoma

Liver cancer is known to have significant degree of intra-tumoral heterogeneity(ITH)(1).Hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(ICC)are major forms of primary liver cancer,accounting for>95%of cases.ITH is linked,as least in part,to the aggressiveness and refractoriness of liver cancer,rendering its high lethality among human malignancies(2).The complex tumor microenvironment promotes tumor progression and contributes to poor treatment response.Hence,it is vital to address the biological mechanisms underlying liver cancer progression and treatment response analyzing the cells in high resolution rather than the mixture of many cell types.Recent advances in single-cell RNA sequencing(scRNA-seq)provide an avenue to dissect liver cancer in an unprecedented degree of high resolution to characterize the underlying pathogenesis and heterogeneity.