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分析 Septin9 基因甲基化在老年原发性肝癌诊断和治疗中的作用。

Analyzing the Role of Septin9 Gene Methylation in the Diagnosis and Treatment of Primary Liver Cancer in the Elderly.

出版信息

Altern Ther Health Med. 2023 May;29(4):194-199.

Abstract

CONTEXT

Because the early symptoms of primary hepatocellular carcinoma (PHC) aren't significant, it's difficult to diagnose it by routine inspection clinically, and if the lesion's diameter is small, less than 2.0 cm, false negatives can occur in pathological examinations. Researchers need to actively search for more diagnostic methods.

OBJECTIVE

The study intended to detect and analyze the value of plasma Septin9 gene methylation for the diagnosis and therapeutic monitoring of PHC in older adults.

DESIGN

The research team performed a prospective controlled study.

SETTING

The study took place at the First Hospital of Qiqihar, an Affiliated Qiqihar Hospital at Southern Medical University in Qiqihar, China.

PARTICIPANTS

Participants were 32 patients with PHC and 28 with cholangiocarcinoma (CCA) who had been admitted to the hospital between January 2021 and July 2022 and 40 healthy individuals.

GROUPS

The research team divided participants into three groups: (1) patients with PHC, the PHC group; (2) patients with CCA, the CCA group; and (3) healthy individuals, the control group.

OUTCOME MEASURES

The research team: (1) determined the positive expression rate of Septin9 gene methylation; (2) measured liver function indicators-alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum total bilirubin (TBIL), direct bilirubin (DBIL), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), albumin (ALB); and (3) measured tumor markers-alpha-fetoprotein (AFP), carbohydrate antigen (CA) 199, CA125, and CA153. The team also: (1) established a binary logistic regression model based on levels of GGT and plasma Septin9 gene methylation to analyze risk factors and diagnosis accuracy, (2) created a receiver operating characteristic (ROC) curve to analyze diagnostic values; and (3) during followup, analyzed the negative conversion rate of Septin9 gene methylation in participants.

RESULTS

The positive expression rate of Septin9 methylation in the PHC group was significantly lower than that that of the CCA group and significantly higher than that of the control group (P < .05). The PHC group's ALT, AST, TBIL, DBIL, ALP, and GGT were significantly higher than those of the control group but significantly lower than those of the CCA group (all P < .05). PHC group's ALB was significantly lower than that of the control group (P < .05). The PHC group's AFP, CA199, and CA125 were significantly higher than those of the control group, and the PHC group's CA199 and CA125 were significantly lower than those in the CCA group (all P < .05). The positive expression of Septin9 gene methylation and the high expression of GGT were risk factors for PHC (OR>1, P < .05). The AUC of the Septin9 gene methylation, the GGT level, and the combined detection of both variables (all AUC > 0.70), suggests that the variables have a diagnostic value in the detection of PHC, with the combined detection having the highest value. The negative conversion rate after surgery of Septin9 gene methylation was 87.10%, for 27 out of 31 participants in the PHC and CCA groups (χ2 = 29.405, P < .001).

CONCLUSION

Plasma Septin9 gene methylation is a sensitive molecular marker for the diagnosis and therapeutic monitoring of older adults with PHC, and combined with the serum GGT level, has a high diagnostic efficiency, which may reflect the treatment status of patients.

摘要

背景

原发性肝细胞癌(PHC)的早期症状并不明显,临床上常规检查很难诊断,而且病变直径小于 2.0cm 时,病理检查可能出现假阴性。研究人员需要积极寻找更多的诊断方法。

目的

本研究旨在检测和分析血浆 Septin9 基因甲基化在老年原发性肝细胞癌(PHC)诊断和治疗监测中的价值。

设计

本研究团队进行了一项前瞻性对照研究。

地点

研究地点位于中国齐齐哈尔市,齐齐哈尔医学院附属第一医院。

参与者

参与者为 2021 年 1 月至 2022 年 7 月期间收治的 32 例 PHC 患者和 28 例胆管癌(CCA)患者,以及 40 名健康个体。

分组

研究团队将参与者分为三组:(1)PHC 患者,PHC 组;(2)CCA 患者,CCA 组;(3)健康个体,对照组。

观察指标

研究团队:(1)确定 Septin9 基因甲基化的阳性表达率;(2)测量肝功能指标-丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、血清总胆红素(TBIL)、直接胆红素(DBIL)、碱性磷酸酶(ALP)、γ-谷氨酰转肽酶(GGT)、白蛋白(ALB);(3)测量肿瘤标志物-甲胎蛋白(AFP)、碳水化合物抗原(CA)199、CA125 和 CA153。团队还:(1)根据 GGT 水平和血浆 Septin9 基因甲基化建立二元逻辑回归模型,分析危险因素和诊断准确性;(2)创建受试者工作特征(ROC)曲线分析诊断价值;(3)在随访期间,分析参与者 Septin9 基因甲基化的阴性转化率。

结果

PHC 组 Septin9 甲基化的阳性表达率明显低于 CCA 组,明显高于对照组(P <.05)。PHC 组的 ALT、AST、TBIL、DBIL、ALP 和 GGT 明显高于对照组,但明显低于 CCA 组(均 P <.05)。PHC 组的 ALB 明显低于对照组(P <.05)。PHC 组的 AFP、CA199 和 CA125 明显高于对照组,CA199 和 CA125 明显低于 CCA 组(均 P <.05)。Septin9 基因甲基化的阳性表达和 GGT 高表达是 PHC 的危险因素(OR>1,P <.05)。Septin9 基因甲基化、GGT 水平和两者联合检测的 AUC(均 AUC > 0.70)表明,这些变量在 PHC 的检测中具有诊断价值,联合检测具有最高的价值。PHC 和 CCA 组中 31 例患者中的 27 例(χ2 = 29.405,P <.001)在手术后 Septin9 基因甲基化的阴性转化率为 87.10%。

结论

血浆 Septin9 基因甲基化是老年原发性肝细胞癌(PHC)诊断和治疗监测的敏感分子标志物,与血清 GGT 水平联合具有较高的诊断效率,可能反映患者的治疗状态。

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