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Overexpression of glucosylceramide synthase and its significance in the clinical outcome of non-small cell lung cancer

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Chinese Medical Journal 2014年第17期127卷 3071-3076页

作者： Zhang Caiqing Lin Xiaoyan Song Yinghua Zhang Xiaofang Li Hongjia Wang Qiangxiu Department of Respiratory Medicine Shandong Provincial Qianfoshan Hospital Shandong University Jinan Shandong 250014 China Department of Pathology Shandong Provincial Hospital Affiliated to Shandong University Jinan Shandong 250021 China Department of Pathology School of Medicine Shandong University Jinan Shandong 250012 China

Background glucosylceramide synthase （GCS）,an enzyme responsible for ceramide glycosylation,plays an important role in multidrug resistance （MDR） in some tumors in vitro; however,its expression and clinicopathological significance in non-small cell lung cancer （NSCLC） remains *** We evaluated GCS expression in 116 paired tumor and adjacent non-cancerous tissues and 50 frozen tissues from patients with NSCLC using immunohistochemistry and western blotting,and explored the correlation between GCS and NSCLC clinicopathological characteristics and *** observed the association between GCS and the MDR proteins P-glycoprotein （P-gp） and lung resistance-related protein （LRP） to determine the link between GCS and MDR at the histological *** GCS expression was significantly upregulated in NSCLC tumors compared with non-cancerous *** was high GCS expression in 75/116 tumor specimens （64.7％） and 16/116 non-cancerous specimens （13.8％）.High GCS expression was significantly associated with poor differentiation （P=0.01）,lymph node metastasis （P=0.004）,recurrence/ distant metastasis （P=0.006）,and chemotherapy resistance （P=0.025）.Multivariate analysis demonstrated that GCS immunopositivity was an independent risk factor for survival （P=0.018）.P-gp was expressed in 80/116 tumors （69.0％） and in 12/116 non-cancerous tissue specimens （10.3％; P=0.001）; LRP was expressed in 85/116 tumors （73.3％） and 19/116 non-cancerous tissue specimens （16.4％; P=0.001）.Importantly,the results demonstrated that increased GCS expression in NSCLC cancer specimens correlated with increased expression of P-gp and LRP,molecules known to stimulate cancer cell MDR （r=0.612 and 0.503,P=0.01 and 0.035,respectively）.Conclusion GCS upregulation might contribute to the development of NSCLC and could be a useful prognostic indicator and chemoresistance predictor for NSCLC patients.

关键词： glucosylceramide synthase non-small cell lung cancer multidrug resistance P-glycoprotein lung resistant-related protein

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Upregulation of glucosylceramide synthase protein in papillary thyroid carcinoma

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Chinese Medical Journal 2013年第24期126卷 4660-4664页

作者： ZHANG Ke SONG Ying-hua L1N Xiao-yan WANG Qiang-xiu ZHANG Hua-wei XU Jia-wen Department of Nuclear Medicine Department of Pathology Department of Nuclear Medicine Department of Ultrasonography Department of Nuclear Medicine Shandong Provincial HospitalAffiliated to Shandong University Jinan Shandong 250021 China Department of Respiratory Medicine Shandong ProvincialQianfoshan Hospital Shandong University Jinan Shandong 250014China

Background glucosylceramide synthase （GCS） can reduce ceramide levels and help cells escape ceramide-induced apoptosis, thus leading to multidrug resistance （MDR）. However, its expression and clinical significance in thyroid neoplasms still remain unclear. We aimed to elucidate the expression of GCS and explore its correlation with the clinicopathological characteristics in papillary thyroid carcinomas （PTCs）. Methods We retrospectively investigated GCS protein expression level in tissue specimens obtained from 108 consecutive PTC patients by immunohistochemistry and Western blotting. Results GCS was weakly positive or negative in normal follicular cells, but it was frequently overexpressed in PTC cells. GCS overexpression was associated with primary tumor size, local infiltration, lymph node metastasis, and local recurrence, but not associated with gender, age, pathological variants, tumor multifocality, tumor stage or distant metastasis. Western blotting also showed that GCS protein levels were much higher in PTCs＇ tissues than in normal thyroid tissues. Conclusion GCS was upregulated in PTCs and might be an independent factor affecting prognosis.

关键词： glucosylceramide synthase papillary thyroid carcinoma, immunohistochemistry Western blotting

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