title: NPTX2 is associated with neoadjuvant therapy response in rectal cancer.
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.
  
  
  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.
authors.affiliation: Department of Colorectal Surgery, Cleveland Clinic, Cleveland, Ohio; Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Georgios
authors.initials: G
authors.lastname: Karagkounis
authors.affiliation: Department of Colorectal Surgery, Cleveland Clinic, Cleveland, Ohio; Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Leo
authors.initials: L
authors.lastname: Thai
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Jennifer
authors.initials: J
authors.lastname: DeVecchio
authors.affiliation: Department of Colorectal Surgery, Cleveland Clinic, Cleveland, Ohio; Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Gantt
authors.affiliation: Department of Colorectal Surgery, Cleveland Clinic, Cleveland, Ohio; Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Duraes
authors.affiliation: Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Rish K
authors.initials: RK
authors.lastname: Pai
authors.affiliation: Department of Colorectal Surgery, Cleveland Clinic, Cleveland, Ohio; Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, Ohio. Electronic address: kaladym@ccf.org.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Kalady
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism*; D059186:Chemoradiotherapy, Adjuvant; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012004:Rectal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012007:Rectum / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis; D016896:Treatment Outcome; D000099153:Pentraxins
chemical_list: D014408:Biomarkers, Tumor; D002097:C-Reactive Protein; D009419:Nerve Tissue Proteins; D000099153:Pentraxins
keywords: Chemoradiation; Complete response; NPTX2; Rectal cancer; Resistance