NPTX2 is associated with neoadjuvant therapy response in rectal cancer
JOURNAL OF SURGICAL RESEARCH
Authors: Karagkounis, Georgios; Thai, Leo; DeVecchio, Jennifer; Gantt, Gerald A.; Duraes, Leonardo; Pai, Rish K.; Kalady, Matthew F.
Abstract
Background: Neoadjuvant chemoradiation (CRT) is recommended for locally advanced rectal cancer. Tumor response varies from pathologic complete response (pCR) to no tumor regression. The mechanisms behind CRT resistance remain undefined. In our previously generated complementary DNA microarrays of pretreatment biopsies from rectal cancer patients, neuronal pentraxin 2 (NPTX2) expression discriminated patients with pCR from those with residual tumor. As tumor response is prognostic for survival, we sought to evaluate the clinical relevance of NPTX2 in rectal cancer. Materials and methods: Real-time quantitative polymerase chain reaction was used to evaluate NPTX2 messenger RNA expression in individual rectal cancers before CRT. Tumors with NPTX2 expression <50% of normal rectum were defined as NPTX2-low and those with >50% were defined as NPTX2-high. NPTX2 levels were compared to response to therapy and oncologic outcomes using Mann-Whitney, Kruskal-Wallis, chi-square, and Mantel-Cox (log-rank) tests, as appropriate. Results: Rectal cancers from 40 patients were included. The mean patient age was 56.8 years, and 30% were female. pCR was achieved in eight of 40 patients (20%). In these patients, messenger RNA NPTX2 levels were significantly decreased compared to those with residual cancer (fold change 30.4, P = 0.017). Patients with NPTX2-low tumors (n = 13) achieved improved response to treatment (P = 0.012 versus NPXT2-high tumors), with 38.5% and 46.1% of patients achieving complete or moderate response, respectively. Of patients with NPTX2-high tumors (n = 27), 11.1% and 18.5% achieved complete or moderate response, respectively. No recurrence or death was recorded in patients with NPTX2-low tumors, reflecting more favorable disease-free survival (P = 0.045). Conclusions: Decreased NPTX2 expression in rectal adenocarcinomas is associated with improved response to CRT and improved prognosis. Further studies to validate these results and elucidate the biological role of NPTX2 in rectal cancer are needed. (C) 2016 Elsevier Inc. All rights reserved.
The Role of Quantitative NPTX2 Hypermethylation as a Novel Serum Diagnostic Marker in Pancreatic Cancer
PANCREAS
Authors: Park, Joo Kyung; Ryu, Ji Kon; Yoon, Won Jae; Lee, Sang Hyub; Lee, Gyung Yub; Jeong, Kyoung-Sin; Kim, Yong-Tae; Yoon, Yong Bum
Abstract
Objectives: The majority of pancreatic cancers are found to be unresectable, and the only chance for cure lies on early detection and complete resection. Several genes have been discovered to be aberrantly methylated in primary pancreatic cancer tissue, and this cancer DNA can be detected in the plasma. The aims of this study were to develop a novel diagnostic marker based on epigenetic characteristics of pancreatic cancer. Methods: We enrolled 104 patients with pancreatic cancer, 60 with chronic pancreatitis, and 5 with benign biliary stone diseases. The blood samples were collected before surgery or any kinds of treatment modalities. DNA was extracted from the plasma of each patient, and NPTX2 (neuronal pentraxin II) CpG island hypermethylation was examined quantitatively by real-time polymerase chain reaction. Results: NPTX2 hypermethylation levels were significantly higher compared with chronic pancreatitis (P = 0.016). The sensitivity and specificity were 80% and 76%, respectively (cutoff = 0.015). NPTX2 gene hypermethylation level was significantly elevated in correlation with higher American Joint Committee on Cancer stages. Conclusions: The aberrantly methylated NPTX2 gene may help to distinguish between chronic pancreatitis and pancreatic cancer with conventional diagnostic tools and could become a valuable diagnostic marker.