title: Expression of hedgehog pathway components is associated with bladder cancer progression and clinical outcome.
abstract: Hedgehog (Hh) pathway has been implicated in the tumorigenesis of a large number of human tumors. But its effects on the progression and prognosis of bladder cancer remain poorly understood. The aim of this study was to investigate expression patterns of Hh pathway components in bladder cancer and to elucidate their prognostic values in this tumor. The expression of sonic hedgehog (Shh), its receptor Patched (Ptch1), and downstream transcription factor Gli1 in 118 specimens of bladder cancer and 30 specimens of adjacent normal bladder tissue was determined by immunohistochemistry. Statistical analyses were applied to test the relationship between the expression of these three proteins and clinicopathologic features and prognosis. Immunohistochemical staining results showed the localizations of Shh and Ptch1 proteins to be mainly located in the cytoplasm of bladder cancer cells, whereas Gli1 was mainly localized in the nuclear of tumor cells. Additionally, positive expression of Shh, Ptch1 and Gli1 proteins was correlated with pathological stage (P = 0.006, 0.006 and 0.008, respectively), venous invasion (P = 0.01, 0.01 and 0.012, respectively) and lymph node metastasis (P = 0.009, 0.01 and 0.013, respectively), but not with other factors including age, gender, tumor grade and recurrence of superficial cancer. Moreover, patients with positive expression of Shh, Ptch1 and Gli1 proteins respectively showed poorer disease-free (P = 0.002, 0.002 and 0.001, respectively) and overall survival (all P < 0.001) than those with negative expression of these three proteins. Univariate and multivariate analysis of prognostic factors in bladder cancer patients indicated that the expression patterns of Shh, Ptch1 and Gli1 proteins were independent unfavorable prognostic factors (all P < 0.001). This is the first report describing about the correlation between Hh pathway and the prognosis of bladder cancer. Expression of Shh, Ptch1 and Gli1 proteins was greater in bladder cancers than in the adjacent normal tissues. The examination of their expression is potentially valuable in prognostic evaluation of bladder cancer.
authors.affiliation: Department of Urology, Guangzhou First Municipal People's Hospital, Guangzhou Medical College, Guangzhou, 510180, China.
authors.forename: Hui-Chan
authors.initials: HC
authors.lastname: He
authors.forename: Jia-Hong
authors.initials: JH
authors.lastname: Chen
authors.forename: Xi-Bin
authors.initials: XB
authors.lastname: Chen
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Qin
authors.forename: Chao
authors.initials: C
authors.lastname: Cai
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: Liang
authors.forename: Zhao-Dong
authors.initials: ZD
authors.lastname: Han
authors.forename: Qi-Shan
authors.initials: QS
authors.lastname: Dai
authors.forename: Yan-Ru
authors.initials: YR
authors.lastname: Chen
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Zeng
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Zhu
authors.forename: Fu-Neng
authors.initials: FN
authors.lastname: Jiang
authors.forename: Wei-de
authors.initials: WD
authors.lastname: Zhong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D015996:Survival Rate; D014157:Transcription Factors / Q000378:metabolism*; D001743:Urinary Bladder / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D055815:Young Adult; D000071676:Zinc Finger Protein GLI1
chemical_list: D014408:Biomarkers, Tumor; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; C509239:SHH protein, human; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1