Lysophosphatidylcholine acyltransferase 1 (LPCAT1) upregulation in breast carcinoma contributes to tumor progression and predicts early tumor recurrence

Abstract

Breast cancer is the most common cancer in women worldwide. Aberrant lipid metabolism is an established hallmark of cancer cells. The recently isolated lysophosphatidylcholine acyltransferase 1 (LPCAT1), the most important enzyme in membrane biogenesis, has been currently implicated in cancer development and progression. The published literature lacks comprehensive reports on LPCAT1 expression in breast cancer and its impact on patients' outcome. We evaluated the immunohistochemical expression of LPCAT1 in 80 primary breast carcinomas, 24 metastatic lymph nodes, and 30 non-neoplastic breast tissue specimens and statistically analyzed the association between LPCAT1 expression and clinicopathological variables and patients' outcome. LPCAT1 protein was significantly upregulated in primary breast carcinoma and showed a significant ascending pattern being the lowest in normal breast tissues, relatively increased in fibrocystic disease, and the highest in primary carcinoma. LPCAT1 expression was significantly higher at tumor's advancing edge and correlated positively with tumor's grade and TNM stage. Compared to primary tumor, LPCAT1 expression was significantly lower in ductal carcinoma in situ and significantly higher in metastatic lymph nodes. LPCAT1 overexpression was significantly associated with increased proliferative activity, negative estrogen receptor (ER) and progesterone receptor (PR) status, positive human epidermal growth factor receptor 2 (HER2) status, as well as triple-negative and HER2 disease molecular subtypes. Multivariate analysis showed that advanced stage, high grade, and LPCAT1 overexpression were independent predictors of early tumor recurrence. We conclude that LPCAT1 is implicated in breast cancer pathogenesis, evolution, and progression and appears to play a potentially crucial role as a determinant of local invasiveness and metastasis. LPCAT1 is an independent predictor of early tumor recurrence of breast carcinoma and represents a novel prognostic biomarker that reflects underlying biological alterations and thus constitutes a potentially promising target for new therapeutic strategies.

Lysophosphatidylcholine acyltransferase 1 upregulation and concomitant phospholipid alterations in clear cell renal cell carcinoma

“…The results showed that LPCAT1 is up-regulated at both transcript and protein levels in ccRCC tissues, while the LPCAT2, LPCAT3 and LPCAT4 levels were comparable between the two groups. Similarly, higher LPCAT1 expression was reported in several other malignant tumours compared to normal tissues, including colorectal adenocarcinoma [12], prostate cancer [23, 27, 28], hepatocellular carcinoma [22], gastric cancer [29], breast cancer [30] and oral squamous cell carcinoma [31]. …”

Metabolomics-Based Discovery of Molecular Signatures for Triple Negative Breast Cancer in Asian Female Population

“…LysoPC is an abundant extracellular lipid that stimulates cell proliferation. Previous studies have shown that lysoPC is not only significantly altered in BC 28 but can also stimulate cancer cell migration and early tumor recurrence 23,29 . PS is an essential component of human cells and presents mainly on the inner leaflet of the cell membrane; however, the oxidative stress in BC cells can cause the exposure of PS.…”

Recurrent triple-negative breast cancer (TNBC) tissues contain a higher amount of phosphatidylcholine (32:1) than non-recurrent TNBC tissues

“…PC can be synthesized by de novo and remodelling pathways [ 22 ]. In the remodelling pathway, LPCAT 1 is a key enzyme for the production of PC from lyso-phosphatidylcholine (LPC) by re-acylation, and its expression has been reported to increase in breast cancer with shorter survival rates [ 23 ]. Moreover, LPCAT1 is reported to be selective for LPC (16:1) and up-regulated LPCAT 1 increased PC (16:0/16:1) [ 24 ].…”