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PLOS Papers on Cancer Testis Antigen Expression in HCC, Cystic Fibrosis Pathogen, More

In PLOS Genetics, an international team led by investigators at Icahn School of Medicine at Mount Sinai-led team tracks transcriptomic features in hepatocellular carcinoma (HCC), highlighting an apparent driver role for enhanced expression of MAGEA3, a gene coding for the cancer testis antigen MAGE-A. The researchers saw significant cancer testis antigen expression variability within individual HCC tumors when they did RNA sequencing on samples collected across multiple regions in 44 HCC tumors from a dozen individuals. From these results and follow up analyses on larger patient cohorts and mouse models of disease, the authors found that higher-than-usual expression of MAGEA3 and other cancer testis antigens coincided with cancer progression and relatively poor survival outcomes. "This study adds data to a growing field of evidence in support of MAGEA3 as a driver of tumor progression and a potential novel therapeutic target in human cancer," they conclude. GenomeWeb has more on this, here.

For a paper in PLOS Pathogens, researchers from Korea and the UK present findings from a genome-wide association study comparing Pseudomonas aeruginosa populations that persist in cystic fibrosis (CF) patients with P. aeruginosa isolates from non-CF settings. Using genome sequence data for nearly 2,200 P. aeruginosa isolates from individuals with or without CF from the Pseudomonas Genome Database, the team characterized genetic variation in the context of CF, introducing a subset of the CF-related alterations into a non-CF strain. "Our bioinformatics analyses, linked with experimental validation via genetic manipulation and phenotypic investigation of mutants, provides novel insights into the genomic plasticity of PA during chronic CF infection," the authors write, noting that the findings "expand our current understanding of how gene-level changes correlate with mechanisms of PA adaptation to the CF lung environment."

Investigators in Japan search for prognostic expression features related to tumor morphology and microenvironment features in primary central nervous system lymphoma (PCNSL) in a paper appearing in PLOS One. Based on RNA-seq of 31 PCNSL samples, along with corresponding clinical data, the team flagged gene signatures associated with cytoskeleton, cell adhesion, extracellular matrix, and matrix metalloprotease enzyme processes. Although the authors caution that the current findings "are limited due to the small sample size and the status of interest," they suggest that the gene signatures identified "would help understand cancer morphology and microenvironment with patient survival and develop de novo molecular target therapy in PCNSL."

The Scan

Looking for Omicron

NPR reports that SARS-CoV-2 testing in the US has gotten better but also that some experts say more needs to be done to better track the Omicron variant.

Holmes Alleges Abuse

The Associated Press reports that Theranos' Elizabeth Holmes has testified at her wire fraud trial that her business and romantic partner abused her.

Bit More Diverse, But More to Do

While Black and Hispanic patients are more likely to participate in cancer clinical trials than previously, they are still underrepresented, according to US News & World Report.

PNAS Papers on Yeast Gene Silencing, Zika Virus Inhibition, Immunoglobulin Hypermutation

In PNAS this week: gene silencing in Saccharomyces cerevisiae, possible neuroprotective role for SHFL in a mouse model of Zika virus infection, and more.