Original Article Differentially expressed miRNAs in the plasma may provide a molecular signature for aggressive pancreatic cancer
Shadan Ali, Khaldoun Almhanna, Wei Chen, Philip A. Philip, Fazlul H. Sarkar
Department of Pathology1 and Division of Hematology/Oncology, Department of Internal Medicine, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, MI, USA
Received: September 24, 2010; accepted: September, 2010; Epub: September, 2010; Published: January 1, 2011
Abstract: Pancreatic cancer (PC) has the poorest overall survival rate among all human cancers because of late diagnosis and absence of screening tools. We compared the expression profile of microRNAs (miRNAs) in the plasma of patients diagnosed with PC (n=50) with healthy volunteers (n=10). Data was further validated by quantitative real-time PCR and cell-based assays. Thirty-seven miRNAs were down-regulated and 54 were up-regulated in plasma from patients with PC. The expression of miR-21 was significantly higher, and the expression of let-7 family (especially let-7d) and miR-146a was significantly lower in PC. Most interestingly, the expression of miR-21 was correlated with worse survival, and the expression of let-7 was inversely correlated with survival in this pilot study with mixed patient population. Moreover, we found that miR-21 family was markedly over-expressed in chemo-resistant PC cell lines, which was consistent with the plasma data from PC patients. Our previous studies have shown increased expression of miR-21 with concomitant loss of PTEN expression in PC cells, which is consistent with our current findings showing the loss of three additional targets of miR-21 (PDCD4, Maspin and TPM1). These results suggest that identifying and validating the expression of miRNAs in newly diagnosed patients could serve as potential biomarker for tumor aggressiveness, and such miRNAs could be useful for the screening of high-risk patients, and may also serve as targets for future drug development. (AJTR1009003).
Key words: Pancreatic cancer, miR-21, miR-221, Drug Resistance, PTEN, let-7d
Address all correspondence to: Fazlul H. Sarkar, PhD Department of Pathology, Karmanos Cancer Institute Wayne State University School of Medicine 740 Hudson Webber Cancer Research Center, 4100 John R Street Detroit, MI 48201 Tel: 313-576-8327 Fax: 313-576-8389 E-mail: email@example.com