Abstract
Simple SummaryCellular metabolism has become a key determinant of cancer cell and immune cell viability and function. To sustain the enormous anabolic demands, tumors adopt a specialized metabolism different from that of normal cells. Tumor cells synthesize acetyl-CoA by uptake of extracellular acetic acid via acetyl coenzyme A synthetase 2 (ACSS2) to provide a carbon source for tumor cells. We found that the expression level of ACSS2 was significantly higher in CESC patients than in normal cells, and confirmed a positive correlation between the level of immune infiltration and ACSS2, thus ACSS2 as a key enzyme of tumor energy metabolism has become a new focus for researchers.Cervical squamous cell carcinoma (CESC) is one of the most common malignant tumors in women worldwide with a low survival rate. Acetyl coenzyme A synthase 2 (ACSS2) is a conserved nucleosidase that converts acetate to acetyl-CoA for energy production. Our research intended to identify the correlations of ACSS2 with clinical prognosis and tumor immune infiltration in CESC. ACSS2 is highly expressed in many tumors and is involved in the progression and metastasis of these tumors. However, it is not clear how ACSS2 affects CESC progression and immune infiltration. Analysis of the cBioPortal, GEPIA2, UALCAN, and TCGA databases showed that ACSS2 transcript levels were significantly upregulated in multiple cancer types including CESC. Quantitative RT-PCR analysis confirmed that ACSS2 expression was significantly upregulated in human cervical cancer cells. Here, we performed tissue microarray analysis of paraffin-embedded tissues from 240 cervical cancer patients recorded at FIGO/TNM cancer staging. The results showed that ACSS2 and PDL1 were highly expressed in human CESC tissues, and its expression was associated with the clinical characteristics of CESC patients. TIMER database analysis showed that ACSS2 expression in CESC was associated with tumor infiltration of B cells, CD4+ and CD8+ T cells, and cancer-associated fibroblasts (CAF). Kaplan–Meier survival curve analysis showed that CESC with high ACSS2 expression was associated with shorter overall survival. Collectively, our findings establish ACSS2 as a potential diagnostic and prognostic biomarker for CESC.
Highlights
Cervical cancer is one of the most common malignancies in female patients, and despite the improved prognosis through early detection, cervical cancer remains the second most common cause of death in women [1]
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We further tested the mRNA levels of ACSS1~3 in multiple cervical cancer cells and our results revealed that the expression of ACSS2 was higher than the other two genes in Hela and CaSki cells (Figure 5b)
Summary
Cervical cancer is one of the most common malignancies in female patients, and despite the improved prognosis through early detection, cervical cancer remains the second most common cause of death in women [1]. Since cancer cells use acetate as a carbon source, ACSS2 is critical for tumor metabolism in a hypoxic and glucose-restricted environment, leading to a shift in metabolism from aerobic glycolysis to oxidative phosphorylation (OXPHOS) [8,10]. It helps cancer cells to survive in a hypoxic environment through lipogenesis [8]. It promotes lipid synthesis and transcription of cell proliferation genes in breast and hepatocellular carcinomas [11,12]. ACSS2 promotes OXPHOS and lipid synthesis in NSCLC and ESCC cells, leading to a metabolic reprogramming and enhanced invasion [13,14]. We attempted to dissect the possible regulatory mechanisms of immune metabolism in CESC through the present study
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