Transcriptomic analysis of pancreatic adenocarcinoma specimens obtained from Black and White patients

被引:3
作者
Biel, Thomas G. G. [1 ]
Petrovskaya, Svetlana [1 ]
Mascia, Francesca [1 ]
Ju, Tongzhong [1 ]
Fashoyin-Aje, Lola [2 ]
Herremans, Kelly M. M. [3 ]
Riner, Andrea N. N. [3 ]
Underwood, Patrick W. W. [3 ]
Gerber, Michael H. H. [3 ,4 ]
Donoghue, Martha [2 ]
Trevino, Jose G. G. [3 ,5 ]
Rao, V. Ashutosh [1 ]
机构
[1] FDA, Ctr Drug Evaluat & Res, Off Biotechnol Prod, Silver Spring, MD 20993 USA
[2] FDA, Ctr Drug Evaluat & Res, Off Oncol Dis, Off New Drugs, Silver Spring, MD USA
[3] Univ Florida, Coll Med, Dept Surg, Gainesville, FL USA
[4] Univ Arizona, Coll Med, Dept Surg, Tucson, AZ USA
[5] Virginia Common wealth Univ, Massy Canc Ctr, Div Surg Oncol, Richmond, VA USA
基金
美国国家卫生研究院;
关键词
CANCER; PROTEIN; DISPARITIES; BIOMARKERS; SURVIVAL; TUMORS;
D O I
10.1371/journal.pone.0281182
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In pancreatic cancer clinical trials, Black patients are under-represented while having higher morbidity and mortality rates as compared to other racial groups. Multiple factors, including socioeconomic and lifestyle factors may contribute to this disparity, but genomic contributions remain unclear. In an exploratory project to identify genes that may contribute to differences in survival between Black (n = 8) and White (n = 20) patients with pancreatic cancer, transcriptomic sequencing of over 24,900 genes was performed in human pancreatic tumor and non-tumor tissue obtained from Black and White patients. Over 4,400 genes were differentially expressed in tumor and non-tumor tissue, irrespective of race. To validate these results, the expression of four genes (AGR2, POSTN, TFF1, and CP) reported to be up-regulated in pancreatic tumor tissue as compared to non-tumor tissue were confirmed using quantitative PCR. Transcriptomic analysis that compared pancreatic tumor tissue from Black and White patients revealed differential expression in 1,200 genes, while a comparison of the non-tumor and tumor gene expression differences within each race revealed over 1,500 tumor-specific differentially expressed genes in pancreatic tumor and non-tumor tissue from Black patients. We identified TSPAN8 as a potential tumor-specific gene significantly overexpressed in pancreatic tumor tissue in Black patients as compared to White patients. Using Ingenuity Pathway Analysis software to compare the race-associated gene expression profiles, over 40 canonical pathways were identified to be potentially impacted by the gene expression differences between the races. Heightened expression of TSPAN8 was associated with poor overall survival, suggesting TSPAN8 as one potential genetic factor contributing to the differential outcomes in Black patients with pancreatic cancer, supporting the potential utility of larger genomic studies to further explore the role of TSPAN8 in pancreatic cancer.
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页数:18
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