Low molecular weight heat shock protein HSP27 is a prognostic indicator in rectal cancer but not colon cancer.
OBJECTIVE
There are currently no biomarkers in routine clinical use for determining prognosis in rectal cancer. In a preliminary proteomic study, variation in the levels of heat shock protein 27 (HSP27) in colorectal cancer samples was observed. The expression of HSP27 in a cohort of 404 patients with colorectal cancer with a predominantly poor prognosis was characterised and an investigation was undertaken of whether the differences were related to clinical outcome. HSP27 levels in diagnostic rectal biopsies were compared with matched surgical samples to determine whether changes in expression occurred in the time between biopsy and surgery and to investigate whether preoperative radiotherapy affected expression. Finally, the relationship between HSP27 expression and outcome was examined in an independent cohort of 315 patients with a predominantly good prognosis.


METHODS
HSP27 levels were determined using combined two-dimensional gel electrophoresis and tandem mass spectrometry (12 cases) and by immunohistochemistry using tissue microarrays of colorectal cancers sampled at surgery and 80 diagnostic rectal biopsies.


RESULTS
HSP27 overexpression was strongly associated with poor cancer-specific survival in rectal cancer (n=205, p=0.0063) but not colon cancer (n=199, p=0.7385) in the cohort with a poor prognosis. Multivariate Cox regression confirmed nodal metastases (p=0.0001) and HSP27 expression (p=0.0233) as independent markers of survival in rectal cancer. HSP27 levels remained unchanged in the majority of cases (65/80, 81%) between diagnostic biopsies and matched surgical samples, regardless of whether patients had undergone preoperative radiotherapy. In the cohort with a good prognosis the association between HSP27 and survival was not observed in patients with either rectal (n=115; p=0.308) or colon cancer (n=200; p=0.713).


CONCLUSIONS
In a large cohort of patients with a poor prognosis, HSP27 is an independent marker of poor outcome in rectal cancer; its expression is not altered by neoadjuvant radiotherapy. This finding requires validation in an independent similar cohort of patients with rectal cancer. HSP27 levels merit evaluation as a stratification factor for treatment of rectal cancer.
Royal Liverpool University Hospital, University of Liverpool, Liverpool, CH48 4DQ, UK.
Elizabeth M
EM
Tweedle
Ilyas
I
Khattak
Chin Wee
CW
Ang
Taoufik
T
Nedjadi
Rosalind
R
Jenkins
B Kevin
BK
Park
Helen
H
Kalirai
Andy
A
Dodson
Bahram
B
Azadeh
Monica
M
Terlizzo
Heike
H
Grabsch
Wolfram
W
Mueller
Sun
S
Myint
Peter
P
Clark
Helen
H
Wong
William
W
Greenhalf
John P
JP
Neoptolemos
Paul S
PS
Rooney
Eithne
E
Costello
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000378:metabolism; D011379:Prognosis; D040901:Proteomics / Q000379:methods; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D055551:HSP27 Heat-Shock Proteins; D009363:Neoplasm Proteins