Up-regulation of lysophosphatidylcholine acyltransferase 1 (LPCAT1) is linked to poor prognosis in breast cancer

溶血磷脂酰胆碱酰基转移酶 1 (LPCAT1) 的上调与乳腺癌预后不良有关

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作者:Patrick Lebok, Aurelia von Hassel, Jan Meiners, Claudia Hube-Magg, Ronald Simon, Doris Höflmayer, Andrea Hinsch, David Dum, Christoph Fraune, Cosima Göbel, Katharina Möller, Guido Sauter, Frank Jacobsen, Franziska Büscheck, Kristina Prien, Till Krech, Rainer Horst Krech, Albert von der Assen, Linn W

Abstract

Dysregulation of lipid metabolism is common in cancer. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has been implicated with various cancer types. Here we analyzed by immunohistochemistry its expression in 2,197 breast cancers. LPCAT1 staining was found in 97.8% of 1,774 interpretable tumors, including 48.1% with weak, 28.7% with moderate, and 14.4% with strong expression. The frequency of LPCAT1 positivity depended on the histological tumor type. Moderate or strong LPCAT1 positivity was more common in cancers of no special type (NST) (46.2%) than in lobular carcinomas (25.9%; p<0.0001). Strong LPCAT1 was associated with BRE grade, tumor cell proliferation and overall survival in all cancers and in the subgroup of NST cancers (p<0.0001, each). In the subset of NST cancers the prognostic effect of LPCAT1 expression was independent of pT, and BRE grade (p<0.0001 each). A comparison with molecular features showed that LPCAT1 was strongly associated with estrogen receptor negativity (p<0.0001), progesterone receptor negativity (p<0,0001), amplification of HER2 (p<0.0001) and MYC (p=0.0066), as well as deletions of PTEN (p<0.0001) and CDKNA2 (p=0.0151). It is concluded that LPCAT1 overexpression is linked to adverse tumor features and poor prognosis in breast cancer. These data also highlight the important role of lipid metabolism in breast cancer biology.

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