Correlation of hedgehog signal activation with chemoradiotherapy sensitivity and survival in esophageal squamous cell carcinomas.
OBJECTIVE
To investigate the significance of hedgehog signaling pathway in chemoradiotherapy sensitivity and its effect on the prognosis of esophageal squamous cell carcinoma.


METHODS
In the present study, we used the method of immunohistochemistry to examine the expression status of two hedgehog components, PTCH1 and glioma-associated oncogene GLI-1, in 100 pre-treated biopsy specimens of esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy.


RESULTS
We find that high levels of PTCH1 and GLI-1 were detected in 76.0 and 72.0% of esophageal squamous cell carcinoma, respectively. Significant associations of high PTCH1 and GLI-1 expression with large tumor size (both P = 0.01), locoregional progression (P= 0.001 and 0.003, respectively) and the lack of complete response to chemoradiotherapy (P= 0.008 and 0.01, respectively) were observed. Univariate analysis revealed that high PTCH1 and GLI-1 expression was associated with poor locoregional progression-free survival, distant progression-free survival and overall survival. Furthermore, esophageal squamous cell carcinoma patients with high PTCH1 and GLI-1 expression have the shorter survival time than the subgroups with negative and low PTCH1 and GLI-1 expression. In multivariate analysis, PTCH1 and GLI-1 expression status were both evaluated as independent prognostic factors for locoregional progression-free survival, distant progression-free survival and overall survival.


CONCLUSIONS
These findings suggest an important role for the activation of hedgehog signaling in esophageal squamous cell carcinoma progression and that PTCH1 and GLI-1 expression may be significantly associated with esophageal squamous cell carcinoma resistance to chemoradiotherapy.
Department of Radiotherapy, First Hospital of Nanjing Medical University, Huaian, Jiangsu 223200, People's Republic of China.
Weiguo
W
Zhu
Zhenbin
Z
You
Tao
T
Li
Changhua
C
Yu
Guangzhou
G
Tao
Mingli
M
Hu
Xiaofei
X
Chen
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011878:Radiotherapy; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015996:Survival Rate; D014157:Transcription Factors / Q000378:metabolism*; D016896:Treatment Outcome; D000071676:Zinc Finger Protein GLI1
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C400551:GLI1 protein, human; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1