Shih-Chieh Chang1,2, Yi-Chun Lai1,2,3, Yen-Chung Chen1,4, Nai-Kuan Wang2, Wei-Shu Wang1,5, Jiun-I Lai1,5,6. 1. School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China. 2. Division of Chest Medicine, Department of Medicine, National Yang-Ming University Hospital, Yilan, Taiwan, Republic of China. 3. Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan, Republic of China. 4. Division of Pathology, Department of Medicine, National Yang-Ming University Hospital, Yilan, Taiwan, Republic of China. 5. Department of Medicine, National Yang-Ming University Hospital, Yilan, Taiwan, Republic of China. 6. Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taiwan.
Abstract
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.
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 humanNSCLC 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 NSCLCpatient 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 NSCLCpatients, and also a possible relationship between CBX3/HP1-gamma expression and EGFR mutation.