title: Gene Expression Analysis of Sporadic Early-Onset Rectal Adenocarcinoma.
abstract: BACKGROUND
  Overall declines in incidence of rectal cancer (RC) in patients older than 50 years have been mostly attributed to improvement in treatment modalities and introduction of age-based screening. Recent studies, however, have shown a rise in the incidence of RC in patients younger than 50 years. The etiology of early-onset (EO) RC is not well understood. The aim of this study is to elucidate the molecular features of (EO) RC and show its uniqueness compared to late-onset (LO) disease.
  
  
  METHODS
  Two cohorts of patients with sporadic RC were identified. Tumors and matching non-involved tissues from six (EO) RC patients (< 50 years) and six (LO) RC patients (>65 years) were obtained from Pathology archives. Deparaffinized tissues were macro-dissected from FFPE sections, RNA isolated and used for expression profiling of 770 cancer related genes representing 13 canonical pathways. Statistical analysis was performed using the Gene Expression R-script module within the nCounter software v2.6. A gene was considered to be above background if the average count for the target gene was greater than the average counts for the eight negative control genes and if the P value of the t-test was less than 0.05.
  
  
  RESULTS
  When we compared rectal tumors to non-involved rectal tissues, changes in expression levels of 171 genes were statistically significant in early-onset group and 151 genes in late-onset group. Further comparative gene expression analysis between early- and late-onset rectal tumors normalized to their matching non-involved tissues revealed that changes in expression of 65 genes were unique to early-onset rectal tumors with 16 genes being up- and 49 genes down-regulated using the cutoff criteria of expression levels difference >2 fold and p-value <0.01. At the pathway level, MAPK signaling was the most deregulated pathway in early-onset rectal tumors compared to PI3K-AKT signaling pathway being the most deregulated in late-onset rectal tumors.
  
  
  CONCLUSIONS
  Results of this study suggest that sporadic early-onset rectal cancer is characterized by distinct molecular events compared to late-onset disease.
authors.affiliation: UA Cancer Center, 1515 N Campbell Avenue, Tucson, AZ 85724, USA; UA Department of Surgery, Division of Surgical Oncology, 1501 N Campbell Avenue, Tucson, AZ 85724, USA.
authors.forename: V
authors.initials: V
authors.lastname: Nfonsam
authors.affiliation: NanoString Technologies, 530 Fairview Avenue North, Seattle, WA 98109, USA.
authors.forename: W
authors.initials: W
authors.lastname: Xu
authors.affiliation: UA Department of Surgery, Division of Surgical Oncology, 1501 N Campbell Avenue, Tucson, AZ 85724, USA.
authors.forename: J
authors.initials: J
authors.lastname: Koblinski
authors.affiliation: UA Cancer Center, 1515 N Campbell Avenue, Tucson, AZ 85724, USA; UA Department of Surgery, Division of Surgical Oncology, 1501 N Campbell Avenue, Tucson, AZ 85724, USA.
authors.forename: J
authors.initials: J
authors.lastname: Jandova
keywords: Gene expression profiling; Pathway analysis; Sporadic early- and late-onset rectal cancer