食管癌高发人群血浆游离DNA中的p38MAPK基因检测研究

doi:10.3969/j.issn.1004-616x.2022.02.005

癌变·畸变·突变 ›› 2022, Vol. 34 ›› Issue (2): 105-109.doi: 10.3969/j.issn.1004-616x.2022.02.005

• 论著 • 上一篇

食管癌高发人群血浆游离DNA中的p38MAPK基因检测研究

冯志寅¹, 吴怡娴², 哈晓丹², 陈邬锦², 李秀梅², 董娟娟²

1. 新疆医科大学第一附属医院病理科, 新疆乌鲁木齐 830011;
2. 新疆医科大学基础医学院, 新疆乌鲁木齐 830011

收稿日期:2021-12-17 修回日期:2022-02-23 发布日期:2022-04-07
通讯作者: 董娟娟,E-mail:JuanJuanDong@163.com E-mail:JuanJuanDong@163.com
作者简介:冯志寅,E-mail:527165537@qq.com。
基金资助:
新疆维吾尔自治区自然科学基金(2018D01C175);省部共建中亚高发病成因与防治国家重点实验室开放课题基金(SKL-HIDCA-2018-26)

Detection of p38MAPK gene in plasma cell-free DNA among patients with high incidence of esophageal cancer

FENG Zhiyin¹, WU Yixian², HA Xiaodan², CHEN Wujin², LI Xiumei², DONG Juanjuan²

1. Department of Pathology, First Affiliated Hospital, Xinjiang Medical University, Urumqi 830011;
2. College of Basic Medicine, Xinjiang Medical University, Urumqi 830011, Xinjiang, China

Received:2021-12-17 Revised:2022-02-23 Published:2022-04-07

摘要/Abstract

摘要： 目的：检测食管癌高发人群哈萨克族食管癌患者血浆游离DNA (cfDNA)中的p38MAPK基因并结合食管癌组织样本中p38MAPK蛋白的表达情况，探讨cfDNA中p38MAPK基因作为食管癌诊断新型分子标志物的意义。方法：收集20例哈萨克族食管癌患者手术治疗前、后的清晨空腹外周静脉血各10mL及相对应患者术后组织的石蜡切片标本，10例健康哈萨克族人群的外周静脉血10mL。离心柱吸附法提取cfDNA，直接PCR法检测cfDNA中的p38MAPK基因。免疫组织化学法检测患者术后组织中p38MAPK蛋白的表达情况并根据患者年龄、性别、分化程度、肿瘤最大径、T分期进行分组比较。结果：哈萨克族食管癌患者手术治疗前、后血液中cfDNA浓度均高于健康哈萨克族人群(P<0.05)；患者手术治疗前cfDNA中p38MAPK基因检出率显著高于健康人群组(P<0.05)，手术后cfDNA中p38MAPK基因检出率与健康人群组差异无统计学意义(P>0.05)；患者术后免疫组化检测结果显示p38MAPK蛋白在高、中分化组中的阳性表达率高于低分化组(χ²=13.939，P<0.05)，在肿瘤最大径≤2.5cm组中的阳性表达率高于>2.5cm组(χ²=0.014，P<0.05)，p38MAPK蛋白的阳性表达率在不同年龄、性别、T分期患者肿瘤组织之间的表达差异无统计学意义(P>0.05)。结论：食管癌高发人群血液中cfDNA浓度显著高于健康人群，提示cfDNA浓度可能用于早期食管癌筛查。哈萨克族食管癌患者血液cfDNA中p38MAPK基因检出率显著高于健康人群组，又提示cfDNA中p38MAPK基因可能作为诊断食管癌的非侵入性新型分子标志物。

关键词: 食管癌, 哈萨克族, 血浆游离DNA, p38MAPK, 循环肿瘤DNA

Abstract: OBJECTIVE：To detect the p38MAPK gene in cell-free DNA (cfDNA) samples among Kazak esophageal cancer patients with high incidence of esophageal cancer， and the p38MAPK protein in cancer tissues， to explore their values as new molecular markers for detecting esophageal cancers. METHODS： Fasting peripheral venous blood samples from 20 Kazak esophageal cancer patients were collected before and after they had surgical treatments，and paraffin sections from the corresponding patients' postoperative tissues were collected. Blood samples from 10 healthy Kazaks were collected as controls. The cfDNA samples were extracted by the centrifugation column adsorption method and used for detection of p38MAPK via direct PCR. Expressions of p38MAPK protein in postoperative tissues were detected using immunohistochemistry and compared according to age， gender， degree of differentiation， maximum tumor diameter and T stage in clinicopathological report. RESULTS：The concentrations of cfDNA in blood of Kazakh with esophageal cancer before and after surgical resections were higher than that of healthy Kazakh (P<0.05). The detection rates of p38MAPK gene in cfDNA before operation were significantly higher than that in healthy population group (P< 0.05). However，there was no significant difference in the detection rates of p38MAPK gene in cfDNA after surgical resection between the two groups (P>0.05). Postoperative immunohistochemical detections show that the positive expression rate of p38MAPK protein in highly and moderately differentiated groups was higher than that in poorly differentiated groups (χ²=13.939， P<0.05). The positive expression rate in the group with maximum tumor diameter ≤2.5 cm was higher than that in the group with maximum tumor diameter >2.5 cm (χ²=0.014，P<0.05). There was no significant difference in the positive expression rates of p38MAPK protein between tumor tissues of patients with different age， sex and T stage(P>0.05). CONCLUSION： The concentrations of cfDNA in the blood of esophageal cancer patients were significantly higher than that of healthy people，suggesting that the concentrationscan possibly be used for early esophageal cancer screening. In addition，the detection rates of the p38MAPK gene in cfDNA of these cancer patients were significantly higher than that of healthy people，suggesting that p38MAPK gene in cfDNA can possibly be used as a potential noninvasive new molecular marker to detect the conditions of esophageal cancers.

Key words: esophageal cancer, Kazak, cfDNA, p38MAPK, ctDNA

中图分类号:

R734.2

冯志寅, 吴怡娴, 哈晓丹, 陈邬锦, 李秀梅, 董娟娟. 食管癌高发人群血浆游离DNA中的p38MAPK基因检测研究[J]. 癌变·畸变·突变, 2022, 34(2): 105-109.

FENG Zhiyin, WU Yixian, HA Xiaodan, CHEN Wujin, LI Xiumei, DONG Juanjuan. Detection of p38MAPK gene in plasma cell-free DNA among patients with high incidence of esophageal cancer[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(2): 105-109.

参考文献

[1] 陈万青, 郑荣寿, 张思维, 等. 2013年中国恶性肿瘤发病和死亡分析[J]. 中国肿瘤, 2017, 26(1): 1-7.
[2] DE ARRUDA HENRY M A C, LERCO M M, RIBEIRO P W, et al. Epidemiological features of esophageal cancer. Squamous cell carcinoma versus adenocarcinoma[J]. Acta Cir Bras, 2014, 29(6): 389-393.
[3] 崔芳芳, 何贤英, 宇传华, 等. 1990—2016年中国人群食管癌疾病负担变化趋势及危险因素分析[J]. 中国卫生统计, 2021, 38(1): 87-91, 95.
[4] 陈晓. 哈萨克族食管癌分子生物学研究进展[J]. 新疆医科大学学报, 2002, 2(2): 19-20.
[5] 董娟娟, 苗娜, 汪慧, 等. 哈萨克族食管鳞癌组织中SM22α的表达及其临床意义[J]. 新疆医科大学学报, 2017, 40(3): 396- 398, 404.
[6] ZHENG S T, VUITTON L, SHEYHIDIN I, et al. Northwestern China: a place to learn more on oesophageal cancer. Part two: gene alterations and polymorphisms[J]. Eur J Gastroenterol Hepatol, 2011, 23(12): 1087-1099.
[7] BIDARD F C, WEIGELT B, REIS-FILHO J S. Going with the flow: from circulating tumor cells to DNA[J]. Sci Transl Med, 2013, 5(207): 207ps14.
[8] CORCORAN R B, CHABNER B A. Application of cell- free DNA analysis to cancer treatment[J]. N Engl J Med, 2018, 379(18): 1754-1765.
[9] AZAD T D, CHAUDHURI A A, FANG P, et al. Circulating tumor DNA analysis for detection of minimal residual disease after chemoradiotherapy for localized esophageal cancer[J]. Gastroenterology, 2020, 158(3): 494-505.e6.
[10] CUENDA A, ROUSSEAU S. p38 MAP-kinases pathway regulation, function and role in human diseases[J]. Biochim Biophys Acta, 2007, 1773(8): 1358-1375.
[11] GAO S G, LIU R M, ZHAO Y G, et al. Integrative topological analysis of mass spectrometry data reveals molecular features with clinical relevance in esophageal squamous cell carcinoma [J]. Sci Rep, 2016, 6: 21586.
[12] 陈红芳, 邓华瑜. JAK/STAT3和MAPK/ERK在乳腺癌细胞侵袭转移中的交互作用及意义[J]. 肿瘤防治研究, 2009, 36(4): 293-297.
[13] LINNSKOG R, JÖNSSON G, AXELSSON L, et al. Interleukin- 6 drives melanoma cell motility through p38α-MAPK-dependent up-regulation of WNT5A expression[J]. Mol Oncol, 2014, 8(8): 1365-1378.
[14] 袁祖阳, 王新峰, 耿潇, 等. 食管癌液态活检: 检测循环游离DNA作为分子标志物是否可行?[J]. 癌症, 2021, 40(7): 279- 292.

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食管癌高发人群血浆游离DNA中的p38MAPK基因检测研究

Detection of p38MAPK gene in plasma cell-free DNA among patients with high incidence of esophageal cancer

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