Clusterin in stool: a new biomarker for colon cancer screening?
OBJECTIVE
The identification of useful markers for early diagnosis of human colon cancer is a major goal still in progress. Clusterin is a pleiotropic protein with a broad range of functions. It has recently drawn much attention because of its association with cancer promotion and metastasis. It is involved in prosurvival and apoptosis processes that are carried out by two different isoforms. Secreted clusterin isoform (sCLU) is cytoprotective and its prosurvival function is the basis of the current phase I/II clinical trials against prostate, lung, and breast cancers. We have already shown that in colorectal cancer (CRC) there is an increased expression of sCLU. In this report, we investigated whether sCLU is released in the blood and stool of colon cancer patients in order to study sCLU as a potential diagnostic molecular marker for colon cancer screening.


METHODS
The quantitative expression of sCLU was determined by dot blot immunodosage in the serum and stool of CRC patients (n=63) and age-matched controls without clinical history of neoplasia, CRC, or systemic or bowel inflammatory disease (n=50). Unpaired t-tests and Mann-Whitney U-tests were used for continuous variables. The diagnostic performance of clusterin was appraised by means of receiver operating characteristic (ROC) curves.


RESULTS
We found a significant increase of sCLU in the serum and stool of CRC patients (P=0.0002 and P<0.000, respectively) as compared with controls. ROC curves provided cutoff points showing a trade-off between sensitivity and specificity. With a cutoff point of 88.5 microg/ml, sCLU in blood showed a 55.6% sensitivity and 100% specificity, and with a cutoff point of 34.6 microg/g, the stool test reached 66.7% sensitivity and 84% specificity in discriminating between nonneoplastic and colorectal neoplastic lesions. Human cancer xenografts in nude mice indicated a positive correlation between increasing serum clusterin level and tumor size.


CONCLUSIONS
This study highlights the potential of clusterin detection in stool to be a valuable tool to improve the effectiveness and efficiency of large-scale clinical cancer screening.
Pucci
Sabina
S
Department of Biopathology, University of Rome Tor Vergata, Rome, Italy. sabina.pucci@uniroma2.it
Bonanno
Elena
E
Sesti
Fabiola
F
Mazzarelli
Paola
P
Mauriello
Alessandro
A
Ricci
Federico
F
Zoccai
Giuseppe Biondi
GB
Rulli
Francesco
F
Galatà
Gabriele
G
Spagnoli
Luigi G
LG
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D015153:Blotting, Western; D051152:Clusterin / Q000032:analysis* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000453:epidemiology; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000453:epidemiology; D055088:Early Detection of Cancer / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D005240:Feasibility Studies; D005243:Feces; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D010865:Pilot Projects; D011336:Probability; D012372:ROC Curve; D012680:Sensitivity and Specificity; D017678:Sex Distribution; D018709:Statistics, Nonparametric
D014408:Biomarkers, Tumor; D051152:Clusterin