Abstract
To investigate the expression and the clinical implications of metabolism-related proteins in lacrimal gland adenoid cystic carcinoma (ACC) in comparison with salivary gland ACC.
Human tissue samples of lacrimal gland ACC (n = 11) and salivary gland ACC (n = 64) were analyzed. Immunochemistry was used to measure expression of proteins related to glycolysis (glucose transporter 1, hexokinase II, carbonic anhydrase IX, and monocarboxylate transporter 4 [MCT4]), glutaminolysis (glutaminase 1 [GLS1], glutamate dehydrogenase [GDH], and amino acid transporter 2 [ASCT2]), mitochondria (adenosine triphosphate [ATP] synthase, succinate dehydrogenase A [SDHA], and succinate dehydrogenase B), and glycolytic intermediate metabolism (phosphoserine phosphatase [PSPH], serine hydroxymethyl transferase 1 [SHMT1]).
GLS1 and ASCT2 were more highly expressed, and GDH, ATP synthase, and SDHA were expressed to a lesser degree in lacrimal gland ACC than in salivary gland ACC (P < .05). Lacrimal gland ACC showed less of a mitochondrial phenotype than did salivary gland ACC (P = .001). Positivity of MCT4 and PSPH was related to shorter disease-free survival, and SHMT1 was related to shorter overall survival (P < .05).
Lacrimal gland ACC exhibited higher expression of GLS1 and ASCT2, compared with salivary gland ACC. Overexpression of MCT4, PSPH, and SHMT1 was associated with poorer prognosis.
摘要
研究相对于唾液腺腺样囊性癌(ACC)来说,泪腺ACC中代谢相关蛋白的表达及临床意义。
用人体组织样本,对泪腺腺样囊性癌ACC11例(N=11)和唾液腺腺样囊性癌64例(n=64)进行了分析,用免疫组织化学测定下述蛋白的表达:糖酵解相关蛋白(葡萄糖载体1,己糖激酶II,碳酸酐酶IX,单羧酸转运蛋白4【MCT4】)、谷氨酰胺(谷氨酰胺酶1【GLS1】,谷氨酸脱氢酶【GDH】,和氨基酸转运体2【ASCT2】)、线粒体(三磷酸腺苷【ATP】合酶,琥珀酸脱氢酶A【SDHA】和琥珀酸脱氢酶B)和糖酵解中间代谢产物(磷酸丝氨酸磷酸化酶【PSPH】,丝氨酸羟甲基转移酶1【SHMT1】)。
泪腺ACC与唾液腺ACC相比,GLS1和ASCT2更高表达,而GDH、ATP合酶和SDHA均表达程度较轻(P<0.05)。与唾液腺ACC相比,泪腺ACC表现出更少的线粒体表型(P=0.001)。MCT4和PSPH阳性者无病生存期短,SHMT1阳性则总生存期降低(P<0.05)。
泪腺ACC与唾液腺ACC相比,GLS1和ASCT2阳性表达更高。MCT4、PSPH和SHMT1的过表达提示预后不佳。
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