血清外泌体LncRNA ZFAS1与老年局部中晚期不可切除食管癌患者病理特征及同步放化疗敏感性的关系研究-现代医学

血清外泌体LncRNA ZFAS1与老年局部中晚期不可切除食管癌患者病理特征及同步放化疗敏感性的关系研究

单位：长江航运总医院肿瘤科, 湖北武汉 430005

分类号：R735.1

出版年·卷·期（页码）：2022·50·第八期（987-994）

摘要：

目的：研究血清外泌体长链非编码RNA ZNFX1反义RNA 1(LncRNA ZFAS1)与老年局部中晚期不可切除食管癌患者病理特征及同步放化疗(CCRT)敏感性之间的关系。方法：收集2020年5月至2021年7月在我院确诊并接受治疗的142例老年局部中晚期不可切除食管癌患者(食管癌组)放疗前(0 d)和放疗后(105 d)的血液样本，以及同期100例非癌志愿者的血液样本作为非癌对照组，qRT-PCR法检测血清外泌体LncRNA ZFAS1基因水平。食管癌患者均行CCRT，根据临床疗效分为放化疗敏感组和非敏感组。结果：食管癌患者放疗前血清外泌体中LncRNA ZFAS1基因水平明显高于非癌对照组(P＜0.05)，其受试者工作特征(ROC)曲线下面积(AUC)为0.844(95%CI：0.805～0.878)。此外，患者血清外泌体LncRNA ZFAS1水平升高与肿瘤直径＞50 mm 、T_4a/4b分期有关(P＜0.05)。患者放疗后血清外泌体LncRNA ZFAS1基因水平均较放疗前显著降低，且放化疗敏感组患者血清ΔLncRNA ZFAS1明显高于非敏感组患者(P＜0.05)。0 d lncRNA ZFAS1≥2.75、ΔlncRNA ZFAS1≥-0.076是影响食管癌组患者CCRT敏感性的独立危险因素(P＜0.05)。结论：血清外泌体lncRNA ZFAS1与老年中晚期食管癌患者病理特征及CCRT敏感性密切相关，有望成为一个潜在的诊断和监测治疗反应的有效生物分子。

Objective: To study the relationship between serum exosomal long non-coding RNA ZNFX1 antisense RNA 1(LncRNA ZFAS1) and pathological characteristics and sensitivity to concurrent chemoradiotherapy (CCRT) in elderly patients with advanced unresectable esophageal carcinoma.Methods: The blood samples of 142 elderly patients with locally advanced unresectable esophageal cancer diagnosed and treated in our hospital from May 2020 to July 2021 were collected before radiotherapy (0 d) and after radiotherapy (105 d),as well as the blood samples of 100 non-cancer volunteers in the same period as the control.Serum exosomal LncRNA ZFAS1 gene levels were detected by qRT-PCR.Esophageal carcinoma patients were treated with CCRT,and divided into sensitive group and insensitive group according to the improvement of the lesions.Results: The level of LncRNA ZFAS1 gene in the serum exosomal of elderly patients with advanced esophageal cancer before radiotherapy was significantly higher than that of control group (P<0.05).The area under the receiver operating characteristic curve (AUC) of serum exosomal LncRNA ZFAS1 for the diagnosis of advanced esophageal cancer was 0.844(95%CI:0.805-0.878).The increased serum exosomal LncRNA ZFAS1 was significantly correlated with tumor diameter>50 mm and T_4a/4b staging (P<0.05).After radiotherapy,the level of serum exosomal LncRNA ZFAS1 gene in elderly patients with advanced esophageal cancer was significantly lower than that before radiotherapy,and the serum exosomal ΔLncRNA ZFAS1 of patients in the sensitive group was significantly higher than that in the insensitive group (P<0.05).0 d lncRNA ZFAS1 ≥ 2.75,and ΔlncRNA ZFAS1 ≥-0.076 were independent risk factors that affected the CCRT sensitivity of patients with esophageal cancer (P<0.05).Conclusion: Serum exosomal LncRNA ZFAS1 is closely related to pathological characteristics and sensitivity to concurrent chemoradiotherapy in elderly patients with advanced esophageal cancer,and is expected to become a potential effective biomolecule for diagnosis and monitoring treatment response.

参考文献：

[1] SHORT M W, BURGERS K G, FRY V T. Esophageal cancer[J].Am Fam Physician, 2017, 95(1):22-28.
[2] 陈洁,袁志平.吸烟对中晚期食管癌患者放化疗后相关并发症和相关指标及预后的影响[J].东南大学学报(医学版),2019,38(1):47-50.
[3] 王涛,李颖,张西志,等.不可切除食管癌紫杉烷或氟尿嘧啶类联合铂类同步放化疗荟萃分析[J].中华肿瘤防治杂志,2020,27(4):316-325.
[4] LI Z, QIN X, BIAN W, et al. Exosomal lncRNA ZFAS1 regulates esophageal squamous cell carcinoma cell proliferation, invasion, migration and apoptosis via microRNA-124/STAT3 axis[J].J Exp Clin Cancer Res, 2019, 38(1):477-489.
[5] ZHANG S, WANG J, YAO T, et al. LncRNA ZFAS1/miR-589 regulates the PTEN/PI3K/AKT signal pathway in the proliferation, invasion and migration of breast cancer cells[J].Cytotechnology, 2020, 72(3):415-425.
[6] SHI H, LIU Z, PEI D, et al. Development and validation of nomogram based on lncRNA ZFAS1 for predicting survival in lymph node-negative esophageal squamous cell carcinoma patients[J].Oncotarget, 2017, 8(35):59048-59057.
[7] 王琪,章文成,张宝忠,等.食管癌UICC/AJCC第8版临床分期对根治性放疗患者预后评估价值[J].中华肿瘤防治杂志,2019,26(7):483-488.
[8] 薛良军,冯艳,汪楠. miR-20a及HER-2表达对食管癌同步放化疗疗效的预测[J].临床肿瘤学杂志,2019,24(12):1099-1103.
[9] BOLLSCHWEILER E, PLUM P, MONIG S P, et al. Current and future treatment options for esophageal cancer in the elderly[J].Expert Opin Pharmacother,2017,18(10):1001-1010.
[10] 车玲玉,李昂,谢俞宁,等.肿瘤坏死因子超家族15-358T>C变异与食管癌发病风险的相关性[J].中国临床药理学杂志,2021,37(17):2262-2265.
[11] UHLENHOPP D J, THEN E O, SUNKARA T, et al. Epidemiology of esophageal cancer:update in global trends, etiology and risk factors[J].Clin J Gastroenterol, 2020, 13(6):1010-1021.
[12] WATANABE M, OTAKE R, KOZUKI R, et al. Recent progress in multidisciplinary treatment for patients with esophageal cancer[J].Surg Today, 2020, 50(1):12-20.
[13] 田胜伟,张光远,许斌,等. LINC00958与肿瘤预后的Meta分析及生物信息学分析[J].东南大学学报(医学版),2021,40(1):27-33.
[14] O'BRIEN S J, FIECHTER C, BURTON J, et al. Long non-coding RNA ZFAS1 is a major regulator of epithelial-mesenchymal transition through miR-200/ZEB1/E-cadherin, vimentin signaling in colon adenocarcinoma[J].Cell Death Discov, 2021, 7(1):61-74.
[15] ZHANG B, CHEN J, CUI M, et al. LncRNA ZFAS1/miR-1271-5p/HK2 promotes glioma development through regulating proliferation, migration, invasion and apoptosis[J].Neurochem Res, 2020, 45(12):2828-2839.
[16] FENG L L, SHEN F R, ZHOU J H, et al. Expression of the lncRNA ZFAS1 in cervical cancer and its correlation with prognosis and chemosensitivity[J].Gene, 2019, 696:105-112.
[17] HE Z, YAN T, YUAN Y, et al. miRNAs and lncRNAs in echinococcus and echinococcosis[J].Int J Mol Sci, 2020, 21(3):730-750.
[18] LI F, SIMON M C. Cancer cells don't live alone:metabolic communication within tumor microenvironments[J].Dev Cell, 2020, 54(2):183-195.
[19] ZHANG J, LI S, LI L, et al. Exosome and exosomal microRNA:trafficking, sorting, and function[J].Genomics Proteomics Bioinformatics, 2015, 13(1):17-24.
[20] NADERI-MESHKIN H, LAI X, et al. Exosomal lncRNAs and cancer:connecting the missing links[J].Bioinformatics,2019,35(2):352-360.
[21] WANG X, HAO R, WANG F, et al. ZFAS1 promotes cisplatin resistance via suppressing miR-421 expression in oral squamous cell carcinoma[J].Cancer Manag Res, 2020, 12:7251-7262.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录