Microrna Mir-155 Is a Biomarker of Early Pancreatic Neoplasia

Abstract

Aim: Following implementation of Improvement Outcome Guidance (IOG), pancreatic cancer surgery is now mostly performed in major pancreatic referral centers. This may have affected selection for surgery and outcome. We report the effect on workload and mortality rate of centralizing pancreatic surgery for a population of about 3.5 millions to a single Centre. Method: We reviewed activity in 2003 and 2007 (before and after implementation of IOG). Pancreatic surgery was done in 3 hospitals in 2003. In 2007 centralization affected 2.3M population form January, and an additional 1.2M from April 2007. Before centralization the surgical HDU was expanded from 3 to 8 beds. Results: In 2003, there were 67 pancreatic procedures of all types performed by 7 surgeons. In 2007 102 patients diagnosed with a neoplasm were deemed operable, and underwent laparotomy. Only one patient on a cancer pathway failed to meet the 62 day target. Two patients were found to be inoperable, and had palliative bypass. Three surgeons performed 100 resections. A further 10 patients had pancreatic necrosectomy. Of the elective resections 94% were managed in surgical HDU (level 2 critical care). Neo-adjuvant treatment was attempted in 12 borderline pancreatic cancers, 4 were successfully resected, 3 are currently receiving chemotherapy, and in 5 cases there was no improvement and palliative chemoYradio therapy was stopped. Conclusion: Centralization has increased the numbers of patients in this Network offered pancreatic resection for tumor. This has enabled new approaches such as laparoscopic distal pancreatectomy and neoadjuvant treatment for borderline resectable tumors. The inoperability rate is low. Despite wider indications for surgery, the mortality rate has fallen. We conclude that centralization has enabled more patients to benefit from safe surgery for pancreatic neoplasm. emerged as a treatment for pancreatic cancer. One decade has elapsed since its institution. The aim of the study is to detect whether adjuvant G improves survival. Methods: A prospective surgical database from 1985 to 2007 with 1637 records was reviewed and identified 579 patients who underwent resection for PDAC. Median, mean and 1, 3, and 5 year survival were calculated for the entire group; by decades regardless of adjuvant treatment; and by treatment with or without G. Results: The 1, 3 and 5 year survival of resected patients (579) was 66, 26 and 15% respectively, with a mean of 30.8 mo. No significant differences were identified over two decades. Patients who received G (n = 199, 34.5%) compared to NG (n = 379, 65.6%) had a statistically significant increase in survival at 1(80 vs. 55%), 3(35 vs. 20%) and 5(20 vs. 12%) years, with a mean of 37 vs. 27.6 (p G 0.0001). G improved survival in patients with tumors that were moderately differentiated (mean 36.5 vs. 25.5, p G 0.0007), Flavanoids are important components of many fruits and vegetables and are believed to have preventive and therapeutic effects in various human malignancies. We hypothesize that flavanoids may...

MicroRNA functional network in pancreatic cancer: From biology to biomarkers of disease

“…Up-regulation of miR196a, miR-190, miR-186, miR-221, miR-222, miR-200b, miR-15b and miR-95 was detected in a third study with 10 pancreatic cancer cell lines and 17 pairs of pancreatic cancer/normal tissues ). Interestingly, two of the up-regulated miRs, miR-155 and miR-21, were also found significantly elevated in the intraductal papillary neoplasms (IPMN) compared with matched controls (Habbe et al 2009). Considering that IPMN are non-invasive precursor lesions of pancreatic cancer, it was concluded that aberrant expression of these miRs is an early event in the multi-stage progression of the disease.…”

Contribution of microRNA analysis to characterisation of pancreatic lesions: a review

“…In a study performed on cryostat embedded sections, miR-21 and miR-155 had the highest relative fold expression levels in IPMNs versus non-neoplastic pancreas43 and the authors observed that both miRNAs (miR-21 and miR-155) were frequently upregulated within the neoplastic epithelium of IPMNs. In this study, also other eight miRNAs (miR-107, miR-223, miR-181c, miR-181a, miR-221, miR-210, miR-16 and miR-100) were significantly upregulated in IPMN if compared with non-neoplastic pancreas 43…”

“…The most frequent method used for assessing miRNA expression is qRT-PCR 12 13 15 18–21 27 30 31 35 40 41 43 44 49 50 53 55 56 58 61 66 67 70–74 76–80. Several approaches to analyse miRNAs continue to be based on single-gene assays; however, high-throughput technologies can be employed to identify differences in miRNA expression levels between normal and cancerous tissues.…”

“…Thus, the use of a combined ISH/immunohistochemistry assay enables rapid and direct evaluation of changes of miRNA expression within the suspicious cells. In situ techniques are used either as main assay for evaluating miRNA expression in pancreatic lesions visualised at cellular/subcellular level52 57 68 or to confirm results obtained by qRT-PCR or high-throughput technique (eg, miRNA microarray or real-time array) 30 41 43…”

Role of microRNAs in solid tumors

“…57 MiR-155 is also reportedly useful for early detection of intraductal papillary mucinous neoplasm (IPMN). 58 …”