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This Week in BMC Cancer: Jul 23, 2012


In BMC Cancer this week, researchers in Switzerland report their identification of three distinct subgroups of renal cell carcinoma through integrative genome-wide expression profiling. The team combined gene expression data from 97 primary renal cell carcinomas with different pathological features, 15 renal cell carcinoma metastases, and 34 cancer cell lines, and used SNP array analysis to map out the genomic landscape. The researchers found genome-wide expression signatures indicating that renal cell carcinoma should be split into three distinct molecular subgroups, and note that the subgroups remain stable even when randomly selected gene sets included in the cluster analysis. "Notably, the pattern obtained from RCC cell lines was clearly distinguishable from that of primary tumors," the authors write. "SNP array analysis demonstrated differing frequencies of chromosomal copy number alterations among RCC subgroups. [Tissue microarray] analysis with group-specific markers showed a prognostic significance of the different groups."

Also in BMC Cancer this week, researchers in Sweden report on the presence of tumor-associated macrophages in tumor stroma as possible prognostic markers for patients with breast cancer. Using immunohistochemistry and tissue microarrays with tumors from 144 breast cancer patients, the researchers evaluated the extent of infiltrating CD163+ or CD68+ myeloid cells in tumor nest compared to tumor stroma. They found that infiltration of the macrophages was of clinical relevance in tumor stroma, but not in tumor nest. They also found that CD163+ macrophages positively correlated with higher grade, larger tumor size, Ki67 positivity, estrogen receptor negativity, progesterone receptor negativity, triple-negative/basal-like breast cancer, and inversely correlated with luminal A breast cancer. CD68+ macrophages in tumor stroma positively correlated to tumor size and inversely correlated to luminal A breast cancer. "Some CD163+ areas lacked CD68 expression, suggesting that CD163 could be used as a general anti-inflammatory myeloid marker with prognostic impact," the team writes. "CD68 in tumor stroma was an independent prognostic factor for reduced breast cancer specific survival."

Finally in BMC Cancer this week, researchers at the University of Florida report that ephrin-A1, a ligand of EphA2, induces activity in tumor suppressor gene cdx-2 in order to inhibit non-small-cell lung cancer tumor growth. The team determined the expression of EphA2 in various non-small-cell lung cancer cell lines and found that the cell lines overexpressed EphA2. The researchers also determined that treatment with ephrin-A1 significantly downregulated EphA2 expression in the cancer cells, and increased the expression of cdx-2. "Our study suggests that EphA2 signaling up-regulates the expression of the TJ-protein claudin-2 that plays an important role in promoting cell proliferation and tumor growth in NSCLC cells," the team writes. "We conclude that receptor EphA2 activation by ephrin-A1 induces tumor suppressor gene cdx-2 expression which attenuates cell proliferation, tumor growth and thus may be a promising therapeutic target against NSCLC."

The Scan

Self-Reported Hearing Loss in Older Adults Begins Very Early in Life, Study Says

A JAMA Otolaryngology — Head & Neck Surgery study says polygenic risk scores associated with hearing loss in older adults is also associated with hearing decline in younger groups.

Genome-Wide Analysis Sheds Light on Genetics of ADHD

A genome-wide association study meta-analysis of attention-deficit hyperactivity disorder appearing in Nature Genetics links 76 genes to risk of having the disorder.

MicroRNA Cotargeting Linked to Lupus

A mouse-based study appearing in BMC Biology implicates two microRNAs with overlapping target sites in lupus.

Enzyme Involved in Lipid Metabolism Linked to Mutational Signatures

In Nature Genetics, a Wellcome Sanger Institute-led team found that APOBEC1 may contribute to the development of the SBS2 and SBS13 mutational signatures in the small intestine.