Contributions
Abstract: PB1544
Type: Publication Only
Session title: Gene therapy, cellular immunotherapy and vaccination - Biology & Translational Research
Background
Acetyl-CoA acetyltransferase 1 (ACAT1) is an enzyme to catalyze the condensation of two acetyl-CoAs to make acetoacetyl-CoA as well as the reverse reaction. Recently, the abnormal ACAT1 enzyme activity in diverse cancer cell lines was recently reported. Yet, the roles of ACAT1 in malignant progression have been incompletely understood so far.
Aims
The aim of this study was to investigate the function and significance of ACAT1 in tumors.
Methods
In the present study, gene expression analysis is completed through the TIMER2 and GEPIA2 web, based on the combination of the HPA, GTEx, and FANTOM5 datasets. The data of protein expression is acquired from the CPTAC dataset. The statistical significance of survival prognosis is analyzed by log-rank test. Genetic alteration analysis is accomplished by cBioPortal web.
Results
Aberrantly alleviated expression of ACAT1 was detected in multiple tumors at mRNA level compared with normal cells, such as bladder urothelial carcinoma (BLCA), head and neck squamous cell carcinoma (HNSC) et al (Figure 1A). After including the normal tissue of the GTEx dataset as controls, we further evaluated the expression difference of ACAT1 between the normal tissues and tumor tissues of PCPG, SARC, TGCT, et al. ACAT1 expression levels were significantly downregulated (tumor versus normal) in above types of tumor (Figure 1B, P<0.05). Similarly, the outcome of decreased protein level of ACAT1 (tumor versus normal) could be obtained (Figure 1C, P<0.001). Next, we investigated the correlation of ACAT1 expression with the prognosis of patients with different tumors. Stratified ACAT1low patients were observed with significantly shorter overall survival (OS) versus the ACAT1high group in kidney renal clear cell carcinoma (KIRC, P<0.001), kidney renal papillary cell carcinoma (KIRP, P<0.001), brain lower grade glioma (LGG, P=0.019) and liver hepatocellular carcinoma (LIHC, P=0.004) (Figure 1D). Likewise, the shorter disease-free survival (DFS) was shown in ACAT1low patients (Figure 1E). Intriguingly, ACAT1low group showed a better OS and DFS than ACAT1high group in mesothelioma (MESA, P=0.02) and uveal melanoma (UVM, P=0.017), respectively. Then, we observed the genetic alteration status of ACAT1 in different tumor samples of the TCGA cohorts. As shown in Figure 1F, the highest alteration frequency of ACAT1 (>7%) appears for patients with uterine tumors. The types, sites, and case number of the ACAT1 genetic alteration are further presented in Figure 1G. We found that missense mutation of ACAT1 was the main type of genetic alteration (N=48). Additionally, we explored the potential association between genetic alteration of ACAT1 and the clinical survival prognosis of cases with different types of cancer. The data of Figure 1H indicated a better overall survival in cases without altered ACAT1 compared with cases with ACAT1 alteration in variety of malignant, such as esophagogastric carcinoma (P<0.001), prostate cancer (P=0.03) and sarcoma (P=0.04).
Conclusion
Taken together, the present study was the first pan-cancer analysis on the role of ACAT1 in tumors. ACAT1 was down-regulated and conferred independent prognostic significance, highlighting the effectiveness and potential of ACAT1 as a potential target for future therapeutic strategies.
Keyword(s): Prognosis, Tumor suppressor
Abstract: PB1544
Type: Publication Only
Session title: Gene therapy, cellular immunotherapy and vaccination - Biology & Translational Research
Background
Acetyl-CoA acetyltransferase 1 (ACAT1) is an enzyme to catalyze the condensation of two acetyl-CoAs to make acetoacetyl-CoA as well as the reverse reaction. Recently, the abnormal ACAT1 enzyme activity in diverse cancer cell lines was recently reported. Yet, the roles of ACAT1 in malignant progression have been incompletely understood so far.
Aims
The aim of this study was to investigate the function and significance of ACAT1 in tumors.
Methods
In the present study, gene expression analysis is completed through the TIMER2 and GEPIA2 web, based on the combination of the HPA, GTEx, and FANTOM5 datasets. The data of protein expression is acquired from the CPTAC dataset. The statistical significance of survival prognosis is analyzed by log-rank test. Genetic alteration analysis is accomplished by cBioPortal web.
Results
Aberrantly alleviated expression of ACAT1 was detected in multiple tumors at mRNA level compared with normal cells, such as bladder urothelial carcinoma (BLCA), head and neck squamous cell carcinoma (HNSC) et al (Figure 1A). After including the normal tissue of the GTEx dataset as controls, we further evaluated the expression difference of ACAT1 between the normal tissues and tumor tissues of PCPG, SARC, TGCT, et al. ACAT1 expression levels were significantly downregulated (tumor versus normal) in above types of tumor (Figure 1B, P<0.05). Similarly, the outcome of decreased protein level of ACAT1 (tumor versus normal) could be obtained (Figure 1C, P<0.001). Next, we investigated the correlation of ACAT1 expression with the prognosis of patients with different tumors. Stratified ACAT1low patients were observed with significantly shorter overall survival (OS) versus the ACAT1high group in kidney renal clear cell carcinoma (KIRC, P<0.001), kidney renal papillary cell carcinoma (KIRP, P<0.001), brain lower grade glioma (LGG, P=0.019) and liver hepatocellular carcinoma (LIHC, P=0.004) (Figure 1D). Likewise, the shorter disease-free survival (DFS) was shown in ACAT1low patients (Figure 1E). Intriguingly, ACAT1low group showed a better OS and DFS than ACAT1high group in mesothelioma (MESA, P=0.02) and uveal melanoma (UVM, P=0.017), respectively. Then, we observed the genetic alteration status of ACAT1 in different tumor samples of the TCGA cohorts. As shown in Figure 1F, the highest alteration frequency of ACAT1 (>7%) appears for patients with uterine tumors. The types, sites, and case number of the ACAT1 genetic alteration are further presented in Figure 1G. We found that missense mutation of ACAT1 was the main type of genetic alteration (N=48). Additionally, we explored the potential association between genetic alteration of ACAT1 and the clinical survival prognosis of cases with different types of cancer. The data of Figure 1H indicated a better overall survival in cases without altered ACAT1 compared with cases with ACAT1 alteration in variety of malignant, such as esophagogastric carcinoma (P<0.001), prostate cancer (P=0.03) and sarcoma (P=0.04).
Conclusion
Taken together, the present study was the first pan-cancer analysis on the role of ACAT1 in tumors. ACAT1 was down-regulated and conferred independent prognostic significance, highlighting the effectiveness and potential of ACAT1 as a potential target for future therapeutic strategies.
Keyword(s): Prognosis, Tumor suppressor