Clusterin as a predictor for chemoradiotherapy sensitivity and patient survival in esophageal squamous cell carcinoma.
Clusterin (CLU) is frequently overexpressed and correlates closely with chemotherapy and radiotherapy resistance and poor prognosis in many human cancers. However, the significance of CLU expression in chemoradiotherapy (CRT) sensitivity and its effect on the prognosis of esophageal squamous cell carcinoma (ESCC) are still unknown. In the present study, we used the methods of immunohistochemistry and terminal deoxyuridine triphosphate nick-end labeling assay to examine the expression status of CLU and apoptotic index in 110 pretreated biopsy specimens of ESCC patients treated with definitive CRT. High expression of CLU was observed in 42.7% of epithelium and 50.0% of stroma in ESCC. A significant association of high CLU stromal expression with large tumor size (P = 0.012) and locoregional progression (P = 0.001) was observed, and high epithelial expression of CLU showed a significant correlation with the lack of complete response (P = 0.028) and low apoptotic index (P = 0.001). Univariate analysis revealed that high CLU stromal expression was associated with poor locoregional progression-free survival, distant progression-free survival, and overall survival. Furthermore, ESCC patients with high CLU expression in both epithelium and stroma have the shortest survival time among the subgroups of different CLU expression status. In multivariate analysis, CLU stromal expression was evaluated as an independent prognostic factor for locoregional progression-free survival, distant progression-free survival, and overall survival. These findings suggest an important role for CLU, especially in stroma, in ESCC progression, and that high CLU epithelial expression might be a promising predictor of ESCC resistance to CRT.
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
Li-Ru
LR
He
Meng-Zhong
MZ
Liu
Bin-Kui
BK
Li
Hui-Lan
HL
Rao
Yi-Ji
YJ
Liao
Lan-Jun
LJ
Zhang
Xin-Yuan
XY
Guan
Yi-Xin
YX
Zeng
Dan
D
Xie
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D051152:Clusterin / Q000032:analysis / Q000502:physiology*; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
C495242:CLU protein, human; D051152:Clusterin