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

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.

SUBMITTER: Lebok P

PROVIDER: S-EPMC6781992 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Lebok Patrick P von Hassel Aurelia A Meiners Jan J Hube-Magg Claudia C Simon Ronald R Höflmayer Doris D Hinsch Andrea A Dum David D Fraune Christoph C Göbel Cosima C Möller Katharina K Sauter Guido G Jacobsen Frank F Büscheck Franziska F Prien Kristina K Krech Till T Krech Rainer Horst RH von der Assen Albert A Wölber Linn L Witzel Isabell I Schmalfeldt Barbara B Geist Stefan S Paluchoswski Peter P Wilke Christian C Heilenkötter Uwe U Terracciano Luigi L Müller Volkmar V Wilczak Waldemar W Burandt Eike Christian EC

Aging 20190918 18

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 m ...[more]

PMID: 31533087

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Project description:BackgroundEndometrial cancer (EC) is one of the three malignant reproductive tumours that threaten women's lives and health. Glycerophospholipids (GPLs) are important bioactive lipids involved in various physiological and pathological processes, including cancer. Immune infiltration of the tumour microenvironment (TME) is positively associated with the overall survival in EC. Exploring GPL-related factors associated with the TME in endometrial cancer can aid in the prognosis of patients and provide new therapeutic targets.MethodsDifferentially expressed GPL-related genes were identified from TCGA-UCEC datasets and the Molecular Signatures Database (MSigDB). Univariate Cox regression analysis was used to select GPL-related genes with prognostic value. The Random forest algorithm, LASSO algorithm and PPI network were used to identify critical genes. ESTIMATEScore was calculated to identify genes associated with the TME. Then, differentiation analysis and survival analysis of LPCAT1 were performed based on TCGA datasets. GSE17025 and immunohistochemistry (IHC) verified the results of the differentiation analysis. An MTT assay was then conducted to determine the proliferation of EC cells. GO and KEGG enrichment analyses were performed to explore the underlying mechanism of LPCAT1. In addition, we used the ssGSEA algorithm to explore the correlation between LPCAT1 and cancer immune infiltrates.ResultsTwenty-three differentially expressed GPL-related genes were identified, and eleven prognostic genes were selected by univariate Cox regression analysis. Four significant genes were identified by two different algorithms and the PPI network. Only LPCAT1 was significantly correlated with the tumour microenvironment. Then, we found that LPCAT1 was highly expressed in tumour samples compared with that in normal tissues, and lower survival rates were observed in the groups with high LPCAT1 expression. Silencing of LPCAT1 inhibited the proliferation of EC cells. Moreover, the expression of LPCAT1 was positively correlated with the histologic grades and types. The ROC curve indicated that LPCAT1 had good prognostic accuracy. Receptor ligand activity, pattern specification process, regionalization, anterior/posterior pattern specification and salivary secretion pathways were enriched as potential targets of LPCAT1. By using the ssGSEA algorithm, fifteen kinds of tumor-infiltrating cells (TICs) were found to be correlated with LPCAT1 expression.ConclusionThese findings suggested that LPCAT1 may act as a valuable prognostic biomarker and be correlated with immune infiltrates in endometrial cancer, which may provide novel therapy options for and improved treatment of EC.

Dataset Information

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

Publications

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

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