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不同乳腺癌亚型中脂质代谢相关蛋白的差异表达。

Differential expression of lipid metabolism-related proteins in different breast cancer subtypes.

作者信息

Kim Sewha, Lee YuKyung, Koo Ja Seung

机构信息

Department of Pathology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea.

出版信息

PLoS One. 2015 Mar 9;10(3):e0119473. doi: 10.1371/journal.pone.0119473. eCollection 2015.

Abstract

PURPOSE

This study aimed to determine the expression and clinical significance of proteins that are involved in lipid metabolism in human breast tumors.

METHODS

Tumors from 476 breast cancer patients were used to construct tissue microarrays. Then, immunohistochemistry (IHC) for hormone-sensitive lipase (HSL), Perilipin 1 (PLIN1), fatty acid binding protein 4 (FABP4), carnitine palmitoyltransferase IA (CPT-1A), acyl-CoA oxidase 1 (ACOX-1), and fatty acid synthase (FASN) was performed on these microarrays.

RESULTS

Breast tumors were classified into 4 subtypes: luminal A (n = 242; 50.8%), luminal B (n = 134; 28.2%), human epidermal growth factor receptor 2 (HER2) (n = 50; 10.5%), and triple negative breast cancer (TNBC) (n = 50; 10.5%). The expression of PLIN1 (p < 0.001), FABP4 (p = 0.029), CPT-1A (p = 0.001), ACOX-1 (p < 0.001), and FASN (p < 0.001) differed significantly among these tumor subtypes. Notably, PLIN1, CPT-1A, and FASN expression was highest in HER2 tumors and lowest in TNBC tumors. Similarly, the expression of FABP4 and ACOX-1 was highest in HER2 tumors and lowest in luminal A tumors. In addition, ACOX-1 positivity was associated with significantly shorter overall survival (p = 0.018). When tumor subtype was considered, FABP4 positivity was associated with significantly shorter disease-free survival (p = 0.005) and overall survival (p = 0.041) in TNBC.

CONCLUSION

Lipid metabolism-related proteins are differentially expressed in different IHC subtypes of breast cancer and some are associated with decreased survival rates.

摘要

目的

本研究旨在确定参与人类乳腺肿瘤脂质代谢的蛋白质的表达及其临床意义。

方法

利用476例乳腺癌患者的肿瘤构建组织芯片。然后,对这些芯片进行激素敏感性脂肪酶(HSL)、围脂滴蛋白1(PLIN1)、脂肪酸结合蛋白4(FABP4)、肉碱棕榈酰转移酶IA(CPT-1A)、酰基辅酶A氧化酶1(ACOX-1)和脂肪酸合酶(FASN)的免疫组织化学(IHC)检测。

结果

乳腺肿瘤分为4种亚型:腔面A型(n = 242;50.8%)、腔面B型(n = 134;28.2%)、人表皮生长因子受体2(HER2)型(n = 50;10.5%)和三阴性乳腺癌(TNBC)型(n = 50;10.5%)。这些肿瘤亚型中,PLIN1(p < 0.001)、FABP4(p = 0.029)、CPT-1A(p = 0.001)、ACOX-1(p < 0.001)和FASN(p < 0.001)的表达存在显著差异。值得注意的是,PLIN1、CPT-1A和FASN在HER2肿瘤中的表达最高,在TNBC肿瘤中的表达最低。同样,FABP4和ACOX-1在HER2肿瘤中的表达最高,在腔面A型肿瘤中的表达最低。此外,ACOX-1阳性与总生存期显著缩短相关(p = 0.018)。在考虑肿瘤亚型时,FABP4阳性与TNBC患者无病生存期显著缩短(p = 0.005)和总生存期显著缩短(p = 0.041)相关。

结论

脂质代谢相关蛋白在乳腺癌的不同免疫组化亚型中表达存在差异,其中一些与生存率降低有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2fa/4353724/6bff5abe4d64/pone.0119473.g001.jpg

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