Deregulation of apolipoprotein C2 gene in cancer: A potential metabolic vulnerability

Abstract

Dear Editor, Apolipoprotein C2 (APOC2), an activator of lipoprotein lipase, participates in hydrolysis of triglycerides, very low-density lipoproteins, and high-density lipoproteins to release free fatty acids (FA). 1 FA oxidation has emerged as an important source of energy for cancer survival and growth. 2 Patterns of APOC2 genomics and transcriptomic alterations in cancer remained unexplored. Here, we characterize APOC2 deregulation in cancer by analyzing 176 studies (supplementary-methods).In 46706 samples of 34 different cancers (Table S1), amplification, mutation, and deep deletion were the main identified APOC2 alterations (Figure S1A). Approximately 1% (251 patients) had at least one genetic alteration in APOC2 with the highest frequency (9.72%) present in bladder cancer and gene amplification being the most common alteration. The highest frequency of deep deletions in APOC2 occurred in diffuse glioma (1.36%). APOC2 mutations occurred in 2.3% of non-melanoma skin cancer and at lower frequencies in other cancers (Table S2). Among the 26 different APOC2 missense and truncating mutations, two were previously reported in hypertriglyceridemia (Figure S1B; Tables S3 and S4).APOC2 was expressed at significantly higher levels in several malignancies (Figures 1 and S2), such as patient-derived glioblastoma stem cells (33.7-fold, p < 0.0001; Figure 1A), invasive ductal breast cancer (2.9fold, p < 0.0001; Figure 1B), centroblastic lymphoma (10.1fold, p < 0.0001; Figure 1C), early stage colorectal tumor (3.8-fold, p = 0.0001; Figure 1D), hypopharyngeal cancer (2.1-fold, p = 0.04; Figure 1E), clear cell renal cell carcinoma (5.9-fold, p < 0.001; Figure 1F), skin squamous cell carcinoma (2.3-fold, p = 0.023; Figure 1G), and gastric cancer (4.8-fold, p = 0.002; Figure 1H) compared with the corresponding normal tissues.

A multi-omics analysis identifies molecular features associated with heifer fertility in a case-control design including Angus and Holstein cattle

“…In mice, the ApoC2 gene is upregulated by high lipid load [90]. In humans, APOC2 is highly abundant in the serum of patients with cancer [91][92][93][94], and the current hypothesis is that APOC2 provides the lipid metabolism, and thus the energy needed for tumorigenesis and tumor progression [94,95]. The protein LCP1 is an actinbinding protein [96] that contributes to actin interaction and assembly in cells [97].…”

Lipids and genes: Regulatory roles of lipids in RNA expression

“…5,6 Growing evidence demonstrates that metabolites and molecules generated during disease-associated lipid metabolism can be an important source to identify and develop new diagnostic biomarkers and therapeutic targets. 1,2,[7][8][9] The clinical lipidomics platform integrates lipidomic profiles with clinical phenomes to uncover disease stage-, severity-, duration-and type-specific biomarkers. 10,11 The interaction between lipids and genes plays critical roles in expression and activation of gene-specific lipid proteins and enzymes and lipid metabolism-associated genes, as well as in multi-directional regulations.…”

“…Dysregulation of lipid metabolism contributes to mitochondrial injury and inter‐organelle dysrfunction, 1,2 imbalance between cell proliferation and cell death 3,4 and acceleration of epithelial‐mesenchymal transition and cancer cell metastasis 5,6 . Growing evidence demonstrates that metabolites and molecules generated during disease‐associated lipid metabolism can be an important source to identify and develop new diagnostic biomarkers and therapeutic targets 1,2,7–9 . The clinical lipidomics platform integrates lipidomic profiles with clinical phenomes to uncover disease stage‐, severity‐, duration‐ and type‐specific biomarkers 10,11 .…”

Lipids and Genes: Regulatory roles of lipids in RNA expression

“…5,6 Growing evidence demonstrates that metabolites and molecules generated during diseaseassociated lipid metabolism can be an important source to identify and develop new diagnostic biomarkers and therapeutic targets. 1,2,[7][8][9] The clinical lipidomics platform integrates lipidomic profiles with clinical phenomes to uncover disease stage-, severity-, duration,-and typespecific biomarkers. 10,11 The interaction between lipids and genes plays critical roles in the expression and activation of gene-specific lipid proteins and enzymes and lipid metabolism-associated genes, as well as in multidirectional regulation.…”

“…Dysregulation of lipid metabolism contributes to mitochondrial injury and interorganelle dysfunction, 1,2 imbalance between cell proliferation and cell death, 3,4 and acceleration of epithelial‐mesenchymal transition and cancer cell metastasis 5,6 . Growing evidence demonstrates that metabolites and molecules generated during disease‐associated lipid metabolism can be an important source to identify and develop new diagnostic biomarkers and therapeutic targets 1,2,7–9 . The clinical lipidomics platform integrates lipidomic profiles with clinical phenomes to uncover disease stage‐, severity‐, duration,‐ and type‐specific biomarkers 10,11 .…”