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PLOS Papers on Hepatocellular Carcinoma Immune Cells, Regulatory Prostate Cancer Risk SNPs, More

For a paper in PLOS One, investigators from Jiaotong University and the University of Texas MD Anderson Cancer Center take a look at tumor-infiltrating immune cell features in nearly 1,100 hepatocellular carcinoma (HCC) tumors based on gene expression data crunched using an analytical tool known as CIBERSORT. Based on data for 1,090 paired normal or unpaired tumors assessed for TCGA, the ICGA, or GEO projects, the team saw four broad tumor clusters marked by distinct tumor-infiltrating immune cell subtype sets, including a groups of tumors with lower-than-usual M1 macrophage levels or enhanced regulatory T cell levels that appeared to be linked to poor outcomes. "Such multidimensional analysis have helped us gain a deep understanding of the immune landscape of HCC, identified the relationship between different [tumor-infiltrating immune cell] infiltration patterns, ad immune checkpoint molecules, and its impact on overall survival, providing evidence for immunotherapy and prediction of survival in HCC patients," the authors write.

In PLOS Genetics, researchers from the US and China explore the regulatory consequences of SNPs implicated in prostate cancer risk in prior genome-wide association studies. Using 850 primary prostate tumor samples from the Cancer Genome Atlas project and a study in Seattle, along with nearly 500 benign but tumor-adjacent prostate samples collected the Mayo Clinic, the team saw hints that some 98 of the 147 prostate cancer-associated SNPs they considered could impact expression quantitative trait loci (eQTL), while nearly three dozen risk SNP sites appeared to overlap with methylation quantitative trait loci (meQTL). "The eQTLS and associated [regulated genes, or "eGenes"] provide insight into the molecular biology of [prostate cancer]," the authors report, "and there is strong evidence that DNA methylation plays an important role in eQTL regulation of gene expression in tumors and in benign samples."

A team from Weill Cornell Medicine and the University at Buffalo take a look at enhancer loss-of-function tolerance for another PLOS Genetics paper. With the help of more than 2,000 available whole-genome sequences, the researchers searched for deletions impacting both copies of known enhancer sequences, highlighting more than two dozen loss-of-function-tolerant enhancers. Their analyses suggest those enhancers tended to be tissue-specific, turning up more often in immune-related cells, for example, and often regulated a relatively limited number of genes. Extrapolating from the current results, the authors estimate that more than 3,500 loss-of-function-tolerant enhancers exist in the human genome, while at least loss-of-function alterations affecting at least 129 enhancers are expected to dire phenotypic consequences.