Zhongguo quanke yixue (Nov 2024)
Investigating Serum PARP2 as a Potential Diagnostic Biomarker for Hepatocellular Carcinoma
Abstract
Background Hepatocellular carcinoma (HCC) is the most common malignant liver tumor, with an increasing incidence rate. Since alpha-fetoprotein (AFP), the traditional serum marker for HCC, has a low sensitivity, there is a critical need for novel molecular biomarkers to enable early detection of HCC. Objective To detect the protein expression level of serum polyadenosine diphosphate ribose polymerase 2 (PARP2) in HCC patients in the blood of HCC patients and investigate its potential as a diagnostic marker for HCC. Methods PARP2 mRNA levels of 50 healthy individuals and 371 HCC patients were analyzed in the TCGA database, and the diagnostic efficacy was analyzed by plotting the receiver operating characteristic (ROC) curve of subjects diagnosed with HCC by PARP2 expression. The levels of PARP2 mRNA and protein expression were assessed in both HCC cells and normal hepatocytes. Serum samples from 38 newly diagnosed HCC patients and 38 healthy individuals undergoing physical examinations at the First Affiliated Hospital of Xinjiang Medical University from March 2021 to July 2022 were collected to measure serum PARP2 protein levels by using the enzyme-linked immunosorbent assay (ELISA) method, and their correlation with HCC clinical characteristics was analyzed. Additionally, the characteristics of serum PARP2 expression levels in diagnosing HCC, particularly in alpha-fetoprotein (AFP) -negative HCC (AFP <20 μg/L) was analyzed, and the efficacy of the combination of serum PARP2 and AFP for the diagnosis of HCC in patients with HCC and healthy individuals was evaluated. Results TCGA data showed that PARP2 mRNA expression is higher in malignant tissues compared to paracancerous tissues based on the big data analysis of TCGA (P<0.001). PARP2 mRNA and protein expression levels were higher in HCC cells HepG2 compared to normal hepatocytes WRL68 (P<0.05). HCC patients had higher serum PARP2 protein expression levels compared to healthy individuals (P<0.001). Comparison of serum PARP2 expression levels in those with different lymphatic metastases and tumor counts showed statistically significant differences (P<0.05). The area under the ROC curve (AUC) of serum PARP2 expression level plotted for the diagnosis of HCC was 0.92, with a sensitivity of 76.32%, a specificity of 97.37% and a cut-off value of 19.45 μg/L. Upon serum AFP testing, 21 of the 38 HCC patients were AFP-negative HCC. The AUC of serum PARP2 protein level for diagnosing AFP-negative HCC was 0.95 (95%CI=0.88-1.00), with a sensitivity of 85.71%, a specificity of 97.37%, and a cutoff value of 19.59 μg/L. The diagnostic efficacy of PARP2 in combination with AFP was further evaluated using a "parallel" co-diagnostic approach, the results showed that the diagnostic efficacy of the combined diagnosis of HCC was 92.11%, the specificity was 94.74%, and the AUC was 0.934 2. For AFP-negative HCC patients, the sensitivity of the combined diagnosis was 85.71%, the specificity was 94.74%, and the AUC was 0.902 3. Conclusion PARP2 is highly expressed in HCC and can be used as a biological marker for HCC screening, especially in AFP-negative HCC.
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