Period 1 and estrogen receptor-beta are downregulated in Chinese colon cancers

Int J Clin Exp Pathol. 2015 Jul 1;8(7):8178-88. eCollection 2015.

Abstract

To investigate whether Period 1 (PER1) and Estrogen receptor-beta (ER2) are associated with occurrence and development of Chinese colorectal cancers. By using RT-quantitative PCR, tissue microarray (TMA) and immunohistochemistry, we detected mRNA levels and protein levels of PER1 and ER2 in the cancerous tissues and paired normal adjacent tissues in patients with colorectal cancer. Survival analyses were performed by the Kaplan-Meier method utilizing log-rank test and univariate and multivariate Cox proportional modeling to measure 5-year disease-free survival (DFS) and overall survival (OS). Real-time PCR showed that, the delta Ct value (tumor tissue vs. normal mucosa) of PER1 or ER2 is 8.51 ± 2.81 vs. 7.34 ± 2.08 or 12.39 ± 2.43 vs. 9.76 ± 1.75, expression of PER1 and ER2 decreased significantly in tumor tissues compared with noncancerous mucosas of patients with or without metastasis (both of P values <0.001). Spearman test revealed that PER1 and ER2 were significantly down-regulated in cancerous tissues (r=0.283; P<0.001) which was also confirmed by immunohistochemistry of specimens from 203 colon cancer patients in a TMA format. The reduction of PER1 was associated with gender and distant metastasis (P=0.037 and P<0.001, respectively) whereas the decline of ER2 was associated with age (P=0.043) by analyzing the clinical data. However, we were not capable of detecting any association between PER1 level or ER2 level and overall survival (OS) or disease free survival (DFS). It is the first observation of correlated reduction of PER1 and ER2 in Chinese colon cancers, and they do play a certain role in colorectal cancer.

Keywords: Period 1; chronotherapy; colon Cancer; estrogen receptor-beta; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Asian People / genetics
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Chi-Square Distribution
  • China
  • Colonic Neoplasms / chemistry*
  • Colonic Neoplasms / ethnology
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / mortality
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / surgery
  • Disease Progression
  • Disease-Free Survival
  • Down-Regulation
  • Estrogen Receptor beta / analysis*
  • Estrogen Receptor beta / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Period Circadian Proteins / analysis*
  • Period Circadian Proteins / genetics
  • Proportional Hazards Models
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Risk Factors
  • Sex Factors
  • Time Factors
  • Tissue Array Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers, Tumor
  • ESR2 protein, human
  • Estrogen Receptor beta
  • PER1 protein, human
  • Period Circadian Proteins
  • RNA, Messenger