Elevated serum progastrin-releasing peptide (31-98) level is a predictor of short response duration after hormonal therapy in metastatic prostate cancer.
BACKGROUND
The neuroendocrine (NE) pathway has been attracting attention as a mechanism for the androgen-independent progression because the neuropeptide provokes tumor growth and inhibits apoptosis under androgen-deprived milieu in prostate cancer cells. On the basis that serum progastrin-releasing peptide (ProGRP) is elevated in patients with advanced disease stage, we examined the prognostic value of the neuropeptide.


METHODS
Serum ProGRP status was determined with an enzyme-linked immunosorbent assay (ELISA) in 460 men with benign and malignant prostatic diseases, chronic renal failure, and healthy controls. Seventy patients with metastatic prostate cancer including four patients (5.7%) with NE carcinoma who underwent hormonal therapy were enrolled in the prognostic analyses by Cox proportional hazards model.


RESULTS
The serum status steadily shifted toward predominant expression of ProGRP with the progression of prostate cancer into metastatic and androgen-independent stages. Univariate analysis revealed that the deteriorated performance status (PS) and extent of bony disease (EOD), and high serum alkaline phosphatase (ALP), serum ProGRP, and nadir prostate-specific antigen (PSA) levels were associated with a lower progression-free survival (PFS) rate (P < 0.005). Multivariate analysis demonstrated that PS, serum ProGRP, and nadir PSA held an independent predictive value for PFS (P < 0.05), and all correlated with bone-related factors. Serum ProGRP was the most significant predictor among pre-treatment factors in this model (P = 0.0094).


CONCLUSIONS
The neuropeptide precursor ProGRP is a distinct serum marker that is useful to know the NE milieu and provides prognostic information in patients with advanced prostate cancer. Standard therapy for metastatic prostate cancer may make progress when further studies will clarify the causative link between serum ProGRP level and androgen-independent disease progression.
Yashi
Masahiro
M
Department of Urology, Jichi Medical School, Tochigi, Japan. yashi@jichi.ac.jp
Nukui
Akinori
A
Kurokawa
Shinsuke
S
Ochi
Masanori
M
Ishikawa
Shinya
S
Goto
Kentaro
K
Kobayashi
Yutaka
Y
Muraishi
Osamu
O
Tokue
Akihiko
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000032:analysis*; D019008:Drug Resistance, Neoplasm; D004797:Enzyme-Linked Immunosorbent Assay; D005768:Gastrointestinal Hormones / Q000032:analysis* / Q000096:biosynthesis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging / Q000379:methods*; D010446:Peptide Fragments / Q000032:analysis* / Q000096:biosynthesis; D010455:Peptides / Q000032:analysis*; D011237:Predictive Value of Tests; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D011994:Recombinant Proteins / Q000032:analysis* / Q000096:biosynthesis; D016896:Treatment Outcome
D000728:Androgens; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D005768:Gastrointestinal Hormones; D010446:Peptide Fragments; D010455:Peptides; D011994:Recombinant Proteins; C087079:pro-gastrin-releasing peptide (31-98); D017430:Prostate-Specific Antigen