Affiliations: [a] Departemt of Geriatric Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China | [b] Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Correspondence:
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Corresponding author: Zhu-lin Yang, Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China. Tel.: +86 731 881873 76; Fax: +86 731 84898168; E-mail: yangzhulin8@sina.com.
Abstract: Purpose:Gallbladder cancers are cancers with high disease-specific mortality rates due to the lack of early diagnosis and effective therapy. In this study, we evaluated whether CDC6 and GDF-9 could be a marker for early diagnosis and target therapy. Methods:CDC6 and GDF-9 expressions in 108 gallbladder adenocarcinomas, 15 gallbladder polyps, 35 chronic cholecystitis tissues, and 46 peritumoral tissues were detected using immunohistochemistry (IHC). Results:We demonstrated that positive CDC6 and GDF-9 expressions were significantly higher in adenocarcinomas than that in peritumoral tissues, polyps, and chronic cholecystitis (p < 0.01). Benign lesions with positive CDC6 and negative GDF-9 expression showed moderately- or severely-atypical hyperplasia. The positive rates of CDC6 were significantly lower in cases with well-differentiated adenocarcinoma, small tumor mass, no metastasis of the lymph node, and no invasion of regional tissues (p < 0.05 or p < 0.01). In contrast, GDF-9 expression was significantly lower in the cases with poorly-differentiated adenocaarcinoma, lymph node metastasis, and invasion (p < 0.05 or p < 0.01). Univariate Kaplan-Meier analysis showed that CDC6 (p=0.046) or GDF-9 (p=0.032) expression was associated with decreased overall survival. Multivariate Cox regression analysis showed that increased expression of CDC6 (p=0.042) or decreased expression of GDF-9 (p=0.031) was an independent poor-prognostic predictor in gallbladder adenocarcinoma. Conclusion:CDC6 and GDF-9 might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma. The positive expression of CDC6 and negative expression of GDF-9 have poor-prognosis in gallbladder carcinoma.
