血浆Septin9基因甲基化状态和水平在胃癌患者诊断和预后评估中的应用价值

doi:10.19401/j.cnki.1007-3639.2023.02.009

中国癌症杂志 ›› 2023, Vol. 33 ›› Issue (2): 162-167.doi: 10.19401/j.cnki.1007-3639.2023.02.009

血浆Septin9基因甲基化状态和水平在胃癌患者诊断和预后评估中的应用价值

陈馨宁¹(), 姜惠琴¹, 杨轶慧¹, 虞倩¹, 张春燕¹^,²(), 王蓓丽¹^,², 潘柏申¹, 郭玮¹^,²

1.复旦大学附属中山医院检验科，上海 200032
2.复旦大学附属中山医院厦门医院检验科，福建厦门 361015

收稿日期:2022-06-24 修回日期:2022-10-13 出版日期:2023-02-28 发布日期:2023-03-22
通信作者: 张春燕（ORCID: 0000-0002-0345-6236），硕士，副主任技师，主任。
作者简介:陈馨宁（ORCID: 0000-0002-2614-6003），本科，技师。
基金资助:
国家自然科学基金(81972000);国家自然科学基金(82172348);复旦大学附属中山医院临床研究专项基金(2018ZSLC05);国家自然科学基金青年项目(81902139);复旦大学附属中山医院临床研究专项基金(2020ZSLC54);上海市临床重点专科建设项目(shslczdzk03302);上海市医学重点专科项目(ZK2019B28);厦门市医疗卫生重点项目(YDZX20193502000002);复旦大学附属中山医院青年基金(2021ZSQN38)

Expression of plasma methylated Septin9 gene and its clinical significance in patients with gastric cancer

CHEN Xinning¹(), JIANG Huiqin¹, YANG Yihui¹, YU Qian¹, ZHANG Chunyan¹^,²(), WANG Beili¹^,², PAN Baishen¹, GUO Wei¹^,²

1. Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
2. Department of Laboratory Medicine, Zhongshan Hospital (Xiamen Branch), Fudan University, Xiamen 361015, Fujian Province, China

Received:2022-06-24 Revised:2022-10-13 Published:2023-02-28 Online:2023-03-22
Contact: ZHANG Chunyan.

摘要/Abstract

摘要：

背景与目的： 胃癌是中国常见的恶性肿瘤之一，胃癌诊疗过程中仍缺乏高特异性、高灵敏度的生物标志物。甲基化的Septin9基因（methylated Septin9 gene，mSEPT9）在胃癌患者癌组织中特征性增高。本文旨在探讨胃癌患者血浆mSEPT9的表达及临床意义。方法： 纳入2020年4月—11月在复旦大学附属中山医院检验科检测血浆mSEPT9（PCR荧光探针法）的221例诊断为胃癌的患者以及34例无疾病证据受检者，并应用ΔΔCt法对mSEPT9水平进行相对定量。收集相关临床资料，包括临床病理学资料（患者基本信息和病理学检查结果）和血清蛋白标志物[癌胚抗原（carcinoembryonic antigen，CEA）、糖类抗原（carbohydrate antigen，CA）12-5、CA19-9和CA72-4]并采用配对t检验、χ²检验和受试者工作特征（receiver operating characteristic，ROC）曲线进行分析。结果： mSEPT9在胃癌未治疗人群中的阳性率为35%（28/80），曲线下面积（area under curve，AUC）为0.815 3，灵敏度为35%，特异度为100%。脉管内见癌栓、侵及浆膜层或周围组织和存在淋巴结转移的胃癌患者术前mSEPT9阳性率较高（46.87% vs 12.50%，45.16% vs 14.29%，75.00% vs 40.00%），差异均有统计学意义（P<0.05）。治疗后疾病进展（progressive disease，PD）患者mSEPT9阳性率高于治疗后部分缓解（partial response，PR）和稳定（stable disease，SD）患者（68.75% vs 17.74%），差异有统计学意义（P<0.05）。患者疾病进展前和疾病进展时mSEPT9 ΔΔCt差异均有统计学意义（P <0.05）。结论： 血浆mSEPT9基因检测在胃癌诊断中的灵敏度和特异性较传统血清蛋白标志物（CEA、CA12-5、CA19-9和CA72-4）更优。该标志物能提供严重程度相关信息，且在PD患者中阳性率较高。SEPT9状态和相对定量结果在预测术后病理学分期和治疗反应中具有潜在临床意义。

关键词: Septin9 基因, 甲基化, 胃癌, 血浆, 循环肿瘤DNA

Abstract:

Background and purpose: Gastric cancer is one of the most common malignant tumors in our country. The diagnosis and treatment process of gastric cancer lacks of sensitive and specific biomarker. This study aimed to explore the expression of plasma methylated Septin9 gene (mSEPT9) and its clinical significance in patients with gastric cancer. Methods: From April 2020 to November 2020, 221 patients with gastric cancer and 34 patients with no evidence of disease who visited Zhongshan Hospital Fudan University were enrolled. The status of mSEPT9 was detected by polymerase chain reaction (PCR) fluorescence probe method, and relative mSEPT9 value was determined by the ΔΔCt method. Detailed clinical data including pathological characteristics (patients characteristics and pathology characteristics) and serum biomarkers [carcinoembryonic antigen (CEA), carbohydrate antigen (CA)12-5, CA19-9 and CA72-4] were collected and analyzed. Paired t test, χ² test and receiver operating characteristic (ROC) curve analysis were performed for statistical analysis. Results: The positive rate, sensitivity and specificity of plasma mSEPT9 were 35%, 35% and 100%, respectively in untreated patients with gastric cancer. The positive rate of mSEPT9 was higher in patients with blood vessel invasion, serosa invasion and lymphatic metastasis, which was 46.87% vs 12.50%, 45.16% vs 14.29%, 75.00% vs 40.00%, respectively (P<0.05). The positive rate of mSEPT9 was higher in progressive disease (PD) patients than in partial response (PR) and stable disease (SD) patients, which were 68.75% and 17.74%, the differences were statistically significant (P<0.05). mSEPT9 level before PD and at the time of PD showed statistically significance. Conclusion: Plasma mSEPT9 detection demonstrates a more satisfactory diagnostic performance in gastric cancer than traditional serum biomarkers. The biomarker can provide information regarding severity with high positive rate among PD patients. The status and level of mSEPT9 were of clinical significance in evaluating tumor burden and predicting treatment response.

Key words: Septin9 gene, Methylated, Gastric cancer, Plasma, Circulating tumor DNA

中图分类号:

R735.2

陈馨宁, 姜惠琴, 杨轶慧, 虞倩, 张春燕, 王蓓丽, 潘柏申, 郭玮. 血浆Septin9基因甲基化状态和水平在胃癌患者诊断和预后评估中的应用价值[J]. 中国癌症杂志, 2023, 33(2): 162-167.

CHEN Xinning, JIANG Huiqin, YANG Yihui, YU Qian, ZHANG Chunyan, WANG Beili, PAN Baishen, GUO Wei. Expression of plasma methylated Septin9 gene and its clinical significance in patients with gastric cancer[J]. China Oncology, 2023, 33(2): 162-167.

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参考文献 15

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Characteristic	N	Percentage/%
Median age (range)/year	62 (30-84)
Gender	221
Male	138	62
Female	83	38
Differentiation status	177
Well	2	1
Moderately	42	24
Poorly	133	75
Lauren classification	186
Intestinal type	61	33
Diffuse type	60	32
Mixed type	65	35
HER2	180
Negative	165	92
Positive	15	8

Item	Cut-off value	AUC	Sensitivity/%	Specificity/%	SE	95% CI	P value
CEA	5	0.573 9	25.32	100.00	0.0527 6	0.470 5-0.677 3	0.214 0
CA19-9	34	0.600 1	17.95	97.06	0.0593 4	0.483 8-0.716 3	0.092 9
CA72-4	10	0.562 9	22.78	94.12	0.0559 1	0.453 3-0.672 5	0.290 1
CA12-5	25	0.711 6	16.25	100.00	0.0473 0	0.618 9-0.804 3	0.000 4
mSEPT9	-0.152 1	0.815 3	35.00	100.00	0.0414 1	0.734 2-0.896 5	<0.000 1
Joint	2.852	0.822 2	66.25	96.77	0.382 1	0.747 3-0.897 1	<0.000 1

Item	Group	mSEPT9 positive	mSEPT9 negative	P value
Blood vessel invasion	Yes	15	17	0.025 8
Blood vessel invasion	No	2	14
Perineural invasion	Yes	13	17	0.362 7
Perineural invasion	No	5	13
Depth of invasion	Serosa negative	4	24	0.012 3
Depth of invasion	Serosa positive	14	17
Lymphatic metastasis	Yes	15	18	0.014 8
Lymphatic metastasis	No	5	27

Item	PR+SD	PD	P value
mSEPT9 positive	11	11	0.000 2
mSEPT9 negative	51	5	0.000 2

血浆Septin9基因甲基化状态和水平在胃癌患者诊断和预后评估中的应用价值

Expression of plasma methylated Septin9 gene and its clinical significance in patients with gastric cancer

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