title: Elevated mRNA expression of CHAC1 splicing variants is associated with poor outcome for breast and ovarian cancer patients.
abstract: BACKGROUND
  The role of CHAC1 (cation transport regulator-like protein 1), a recently identified component of the unfolded protein response (UPR) pathway, in gynaecological cancers has not yet been characterised. Now, this work illustrates CHAC1 mRNA expression and associated clinical outcome in breast and ovarian cancer.
  
  
  METHODS
  The prognostic value of CHAC1 and its two transcript variants was investigated in 116 breast and 133 ovarian tissues using quantitative real-time reverse-transcriptase PCR. Subsequently, we conducted functional studies using short-interfering RNA-mediated knockdown and plasmid-mediated overexpression of CHAC1 in breast and ovarian cancer cells.
  
  
  RESULTS
  Poorly differentiated tumours exhibited higher CHAC1 mRNA expression (breast cancer: P=0.004; ovarian cancer: P=0.024). Hormone receptor-negative breast tumours and advanced-staged ovarian cancers demonstrated elevated CHAC1 mRNA expression levels (P<0.001 and P=0.026, respectively). The multivariate survival analysis showed a prognostic value of both transcript variants in breast cancer (transcript variant 1: RR(death) 6.7 (2.4-18.9); P<0.001), RR(relapse) 6.7 (2.1-21.3); P=0.001); (transcript variant 2: RR(death) 4.9 (2.0-12.4); P<0.001), RR(relapse) 8.0 (2.4-26.8); P<0.001). Ovarian cancer patients aged younger than 62.6 years with high CHAC1 mRNA expression showed poorer relapse-free- and overall-survival (P=0.030 and P=0.012, respectively). In functional studies CHAC1 knockdown suppressed cell migration, whereas ectopic overexpression opposed these effects.
  
  
  CONCLUSIONS
  High CHAC1 mRNA expression could be an independent indicator for elevated risk of cancer recurrence in breast and ovarian cancer.
authors: Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck A-6020, Austria.
authors: G
authors: G
authors: Goebel
authors: R
authors: R
authors: Berger
authors: A M
authors: AM
authors: Strasak
authors: D
authors: D
authors: Egle
authors: E
authors: E
authors: Müller-Holzner
authors: S
authors: S
authors: Schmidt
authors: J
authors: J
authors: Rainer
authors: E
authors: E
authors: Presul
authors: W
authors: W
authors: Parson
authors: S
authors: S
authors: Lang
authors: A
authors: A
authors: Jones
authors: M
authors: M
authors: Widschwendter
authors: H
authors: H
authors: Fiegl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D027682:Cation Transport Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D017931:DNA Primers; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D027682:Cation Transport Proteins; D017931:DNA Primers; D012333:RNA, Messenger