血清 PARP2 作为潜在的肝细胞癌诊断标志物的研究
Investigating Serum PARP2 as a Potential Diagnostic Biomarker for Hepatocellular Carcinoma
背景 ?肝细胞癌（HCC）是肝脏最常见的恶性肿瘤，近年 HCC 发病率上升，甲胎蛋白（AFP）是 HCC诊断中的经典血清标志物，其灵敏度低，亟待研发新型分子生物标志物用于 HCC 的早期诊断。目的 ?检测 HCC 患者血清聚腺苷二磷酸核糖聚合酶 2（PARP2）蛋白表达水平，并探讨其是否可以作为潜在的 HCC 诊断标志物。方法 ?在TCGA数据库中分析 50 例健康体检者与 371 例 HCC 患者的 PARP2 mRNA 水平，通过 PARP2 表达量绘制诊断 HCC 的受试者工作特征（ROC）曲线，分析诊断效能。在 HCC 细胞和正常肝细胞中检测PARP2 mRNA表达水平和蛋白水平。收集 2021 年 3 月—2022 年 7 月新疆医科大学第一附属医院新发 HCC 患者的血清样本 38 例及同期体检健康者血清样本 38 例，采用酶联免疫吸附试验（ELISA）方法，检测血清 PARP2 蛋白水平，并分析 HCC 患者血清 PARP2 蛋白水平与临床特征的相关性，分析血清 PARP2 表达水平用于 HCC 诊断与甲胎蛋白（AFP）阴性 HCC（AFP<20 ng/mL）诊断的效能分析，评估血清 PARP2 与 AFP 联合诊断 HCC 患者与健康体检者的效能。结果 ?基于 TCGA 的大数据分析，癌组织PARP2 mRNA表达量高于癌旁组织（P<0.001）；HCC 细胞 HepG2 中 PARP2 mRNA 表达水平、PARP2蛋白表达水平高于正常肝细胞WRL68（P<0.05）。HCC患者血清PARP2蛋白表达水平高于体检健康者（P<0.001）。不同淋巴转移、肿瘤数目者血清PARP2表达水平比较，差异均有统计学意义（P<0.05）。血清 PARP2 表达水平绘制诊断 HCC的 ROC 曲线下面积（AUC）为 0.92，灵敏度为 76.32%，特异度为97.37%，截断值为19.45 ng/mL。经血清 AFP 检测，38 例 HCC 患者中21例为AFP阴性HCC。血清PARP2蛋白水平诊断AFP阴性 HCC 的 AUC 为 0.95（95%CI=0.88~1.00），灵敏度为 85.71%，特异度为97.37%，截断值为19.59 ng/mL。进一步评估PARP2联用AFP的诊断效能，使用“并联”的联合诊断模式，结果显示：联合诊断HCC的灵敏度为92.11%，特异度为94.74%，AUC为0.934 2；针对AFP阴性的HCC患者，联合诊断的灵敏度为85.71%，特异度为94.74%，AUC为0.902 3。结论 ?PARP2在HCC中高表达，可以作为HCC筛查的生物学标志物，尤其是AFP阴性的HCC。
Background ?Hepatocellular carcinomaHCCis the most common malignant liver tumorwith an increasing incidence rate. Since alpha-fetoproteinAFPthe traditional serum marker for HCChas a low sensitivitythere 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 2PARP2in 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 databaseand the diagnostic efficacy was analyzed by plotting the receiver operating characteristicROCcurve 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 assayELISAmethodand their correlation with HCC clinical characteristics was analyzed. Additionallythe characteristics of serum PARP2 expression levels in diagnosing HCCparticularly in alpha-fetoproteinAFP-negative HCCAFP<20 ng/mLwas analyzedand 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 TCGAP<0.001. PARP2 mRNA and protein expression levels were higher in HCC cells HepG2 compared to normal hepatocytes WRL68P<0.05. HCC patients had higher serum PARP2 protein expression levels compared to healthy individualsP<0.001. Comparison of serum PARP2 expression levels in those with different lymphatic metastases and tumor counts showed statistically significant differencesP<0.05. The area under the ROC curveAUCof serum PARP2 expression level plotted for the diagnosis of HCC was 0.92with a sensitivity of 76.32%a specificity of 97.37% and a cut-off value of 19.45 ng/mL. Upon serum AFP testing21 of the 38 HCC patients were AFP-negative HCC. The AUC of serum PARP2 protein level for diagnosing AFP-negative HCC was 0.9595%CI=0.88-1.00 with a sensitivity of 85.71%a specificity of 97.37%and a cutoff value of 19.59 ng/mL. The diagnostic efficacy of PARP2 in combination with AFP was further evaluated using a “parallel” co-diagnostic approachthe 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. For AFP-negative HCC patientsthe 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 screeningespecially in AFP negative HCC.
亚库甫·托合提、赵辉、叶建蔚、麦尔哈巴·麦麦提艾力、张凯楠、吕国栋
10.12114/j.issn.1007-9572.2023.0553
肿瘤学基础医学临床医学
肝肿瘤PARP2甲胎蛋白诊断标志物Wilcoxon 秩和检验
亚库甫·托合提,赵辉,叶建蔚,麦尔哈巴·麦麦提艾力,张凯楠,吕国栋.血清 PARP2 作为潜在的肝细胞癌诊断标志物的研究[EB/OL].(2024-02-19)[2025-08-24].https://chinaxiv.org/abs/202402.00177.点此复制
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