CBX3/heterochromatin Protein 1 Gamma is Significantly Upregulated in Patients with Non-small Cell Lung Cancer

Aim: Lung cancer is typically categorized into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC comprises of the majority of lung cancer with a poor prognosis in advanced cases. Transcriptional profiling studies, including microarrays and RNA-sequencing studies, have significantly enriched our knowledge of gene expression patterns in NSCLC. A recent transcriptional profiling study identified high prevalence of CBX3/HP1-gamma upregulation in human NSCLC samples. CBX3/HP1-gamma is an isoform of the heterochromatin protein 1 family, which plays a role in heterochromatin formation and is linked to cancer.

Methods: We examined lung cancer samples from our hospital using immunohistochemistry for CBX3/HP1-gamma staining. We also analyzed publicly available databases of NSCLC transcriptional profiling to validate our results.

Results: We identified a high prevalence (77.2%) of samples with positive CBX3/HP1-gamma staining by immunohistochemistry in NSCLC patient samples. Independently, we queried a publicly available dataset (GSE40419) containing RNA-seq data from 77 patients. Upregulation of CBX3/HP1-gamma in tumor samples was present in 60.2% of the patients. A similar correlation was also observed in the The Cancer Genome Atlas (TCGA) database. Interestingly, we discovered a highly significant association between positive CBX3/HP1-gamma staining and EGFR mutation in our patient samples (40 of 42 patients, P < 0.001). Treatment of EGFR mutant NSCLC cell lines with the EGFR inhibitor gefitinib failed to yield a change in CBX/HP1-gamma expression, suggesting that CBX/HP1-gamma expression may be independent of EGFR downstream signaling.

Conclusion: We report a significant upregulation of CBX3/HP1-gamma in NSCLC patients, and also a possible relationship between CBX3/HP1-gamma expression and EGFR mutation.