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Chang D.H.,Center for Cancer Research and Genomic Medicine | Rutledge J.R.,Center for Cancer Research and Genomic Medicine | Patel A.A.,Center for Cancer Research and Genomic Medicine | Heerdt B.G.,Center for Cancer Research and Genomic Medicine | And 2 more authors.
PLoS ONE | Year: 2013

The purpose of this study is to evaluate cytokine expression by peripheral blood mononuclear cells (PBMC) from stage I lung cancer patients and to confirm these expression patterns by exposing PBMCs to lung cancer cells in vitro. Five altered cytokines in stage I lung cancer patients (CCL3, IL8, IL1β, CXCL10, sIL2Rα) were identified in plasma from subjects (n = 15) before and after resection using a 30-plex panel protein assay. Gene expression studies using quantitative RT-qPCR were performed on PBMCs from stage I lung cancer patients (n = 62) before and after resection, and compared to non-cancer patients (n = 32) before and after surgery for benign disease. Co-culture experiments that exposed healthy donor PBMCs to lung cancer cells in vitro were performed to evaluate the effect on PBMC cytokine expression. PBMC gene expression of CCL3, IL8 and IL1β was higher in lung cancer patients compared to the same patients at each of four sequential timepoints after removal of their tumors, while CXCL10 and IL2Rα were essentially unchanged. This pattern was also detected when lung cancer patients were compared to non-cancer patients. When non-cancer patients underwent surgery for benign diseases, these cytokine expression changes were not demonstrable. Lung cancer cell lines, but not benign bronchial epithelial cells, induced similar changes in cytokine gene and protein expression by healthy donor PBMCs in an in vitro co-culture system. We conclude that PBMCs from stage I lung cancer patients possess distinct cytokine expression patterns compared to both non-cancer patients, and lung cancer patients following tumor removal. These expression patterns are replicated by healthy donor PBMCs exposed to lung cancer cell lines, but not benign bronchial epithelial cells in vitro. These findings have implications for understanding the immune response to lung cancer. © 2013 Chang et al. Source

Gumireddy K.,Wistar Institute | Li A.,Wistar Institute | Chang D.H.,Center for Cancer Research and Genomic Medicine | Liu Q.,Wistar Institute | And 9 more authors.
Oncotarget | Year: 2015

Cancer testis antigens (CTAs) are widely expressed in tumor tissues, circulating tumor cells (CTCs) and in cancer derived exosomes that are frequently engulfed by lymphoid cells. To determine whether tumor derived CTA mRNAs could be detected in RNA from purified peripheral blood mononuclear cells (PBMC) of non-small cell lung cancer (NSCLC) patients, we assayed for the expression of 116 CTAs in PBMC RNA in a discovery set and identified AKAP4 as a potential NSCLC biomarker. We validated AKAP4 as a highly accurate biomarker in a cohort of 264 NSCLCs and 135 controls from 2 different sites including a subset of controls with high risk lung nodules. When all (264) lung cancers were compared with all (135) controls the area under the ROC curve (AUC) was 0.9714. When 136 stage I NSCLC lung cancers are compared with all controls the AUC is 0.9795 and when all lung cancer patients were compared to 27 controls with histologically confirmed benign lung nodules, a comparison of significant clinical importance, the AUC was 0.9825. AKAP4 expression increases significantly with tumor stage, but independent of age, gender, smoking history or cancer subtype. Follow-up studies in a small number of resected NSCLC patients revealed a decrease of AKAP4 expression post-surgical resection that remained low in patients in remission and increased with tumor recurrence. AKAP4 is a highly accurate biomarker for the detection of early stage lung cancer. Source

Ganepola G.A.P.,Center for Cancer Research and Genomic Medicine | Mazziotta R.M.,Valley Hospital | Weeresinghe D.,Valley Hospital | Corner G.A.,Montefiore Medical Center | And 9 more authors.
Clinical and Experimental Metastasis | Year: 2010

The objective of this study was to gain insights into the biological basis of the metastatic process by characterizing the gene expression differences between primary and metastatic colon cancers. Recent studies have demonstrated that few new mutational changes are acquired during the metastatic progression of colon tumors [Jones et al., Proc Natl Acad Sci USA 105 (11): 4283-4288, 2008]. However, the extent to which epigenetic and transcriptional changes occur between primary and metastatic colon cancer remains unknown. We approached these issues using Affymetrix microarrays to assess the similarities and differences in gene expression profiles between macro-dissected primary and metastatic colon tumors. Unexpectedly, we found that expression of a number of cell proliferation markers were reduced in the liver metastases of colon tumors when compared to primary tumors. This finding was validated by immunohistochemical staining of Ki67 and Cyclin D1 in Formalin-Fixed Paraffin-Embedded (FFPE) section of the same samples, and in an independent cohort of FFPE matched tumor and metastatic tissue samples. These results indicate that significant transcriptional differences exist between primary and metastatic colon tumors, and demonstrate that metastatic lesions have a lower proliferative rate compared to primary tumors. These findings may have implications for interpreting differences in response rates between primary and metastatic lesions and suggest that measurement of expression-based biomarkers in metastatic tissue will be most informative for understanding the basis of response of metastatic tumors to therapeutic intervention. © 2009 Springer Science+Business Media B.V. Source

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