Abstract
BackgroundThe involvement of lipid metabolism in tumourigenesis and the progression of clear cell renal cell carcinoma (ccRCC) have been reported. However, the role of phospholipid profile alterations in ccRCC has not yet been systematically explored. In the present study, we compared the phospholipid compositions between ccRCC and paired normal renal tissues.MethodsThe phospholipid compositions of paired ccRCC and normal renal tissues were evaluated using liquid chromatography tandem mass spectrometry (LC/MS/MS). To evaluate the mRNA and protein levels of lysophosphatidylcholine acyltransferase (LPCAT), which converts lysophosphatidylcholine (LPC) to phosphatidylcholine (PC), qRT-PCR, western blotting and immunohistochemistry were performed. The correlations of LPCAT1 expression with clinicopathological features and prognosis were assessed. In addition, siRNAs were used to knockdown LPCAT1 expression in ccRCC cell lines, and its effect on cell proliferation, cell cycle, migration and invasion were investigated.ResultsThe phospholipid compositions of ccRCC and normal renal tissues were significantly different. Multiple LPC species were decreased and corresponding PC species were increased in cancer tissues. The mRNA and protein levels of LPCAT1 were up-regulated in ccRCC tissues compared with normal renal tissues, and LPCAT1 expression was significantly correlated with unfavourable pathological features (higher tumour grade, higher TNM stage and larger tumour size) and overall survival. In cell line experiments, LPCAT1 knockdown depleted PCs, inhibited cell proliferation, migration and invasion and induced cell cycle arrest at the G0/G1 phase.ConclusionSelective changes in PC and LPC composition were observed in ccRCC tissues. The overexpression of LPCAT1 promotes the development and progression of ccRCC, likely through the conversion of LPC to PC.
Highlights
The involvement of lipid metabolism in tumourigenesis and the progression of clear cell renal cell carcinoma have been reported
Multivariate statistical analyses were performed to identify the difference between clear cell renal cell carcinoma (ccRCC) and normal tissues. Both unsupervised principal component analysis (PCA) and supervised partial least-squares-discriminant analysis (PLS-DA) could discriminate ccRCC tissues from matched normal tissues based on the phospholipid profile (Fig. 1a, b)
As a relatively new concept in oncogenesis, lipid profile alterations have been implicated in the development and progression of various cancers, such as breast cancer, hepatocellular carcinoma and prostate cancer [20,21,22,23]. ccRCC is characterized by sterol storage in the tumour cytoplasm, suggesting that alterations in lipid metabolism may be involved in the formation and progression of this disease
Summary
The involvement of lipid metabolism in tumourigenesis and the progression of clear cell renal cell carcinoma (ccRCC) have been reported. We compared the phospholipid compositions between ccRCC and paired normal renal tissues. Clear cell renal cell carcinoma (ccRCC) is the most common type of renal malignancy in adults. Due to a lack of early-warning signs, approximately 30% of ccRCC patients present with metastatic disease at diagnosis [1, 2]. There are no satisfactory treatment options for patients with advanced-stage disease, as ccRCC is inherently resistant to radiotherapy and chemotherapy [2]. Apart from genetic variation, the involvement of lipid metabolism in the tumourigenesis and progression of ccRCC has recently been suggested. Ohno et al [3] conducted a study enrolling 364 patients with ccRCC and concluded that higher preoperative levels
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