切换至 "中华医学电子期刊资源库"

中华肺部疾病杂志(电子版) ›› 2023, Vol. 16 ›› Issue (06) : 774 -778. doi: 10.3877/cma.j.issn.1674-6902.2023.06.006

论著

肺鳞癌血清外泌体hsa_circ_0018430的表达和临床意义
王志鹏, 张倩, 黄燕华, 孙赟, 方晓明, 施宇佳()   
  1. 213003 常州,南京医科大学附属常州第二人民医院呼吸与危重症医学科
  • 收稿日期:2023-09-11 出版日期:2023-12-25
  • 通信作者: 施宇佳
  • 基金资助:
    常州市卫生健康青苗人才培养工程(CZQM2020077)

Expression and clinical significance of serum exosomal hsa_circ_0018430 in lung squamous cell carcinoma

Zhipeng Wang, Qian Zhang, Yanhuan Huang, Yun Sun, Xiaoming Fang, Yujia Shi()   

  1. Department of Respiratory and Critical Care Medicine, the Affiliated Changzhou NO.2 People′s Hospital of Nanjing Medical University, Changzhou 213003, China
  • Received:2023-09-11 Published:2023-12-25
  • Corresponding author: Yujia Shi
引用本文:

王志鹏, 张倩, 黄燕华, 孙赟, 方晓明, 施宇佳. 肺鳞癌血清外泌体hsa_circ_0018430的表达和临床意义[J]. 中华肺部疾病杂志(电子版), 2023, 16(06): 774-778.

Zhipeng Wang, Qian Zhang, Yanhuan Huang, Yun Sun, Xiaoming Fang, Yujia Shi. Expression and clinical significance of serum exosomal hsa_circ_0018430 in lung squamous cell carcinoma[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2023, 16(06): 774-778.

目的

分析血清外泌体环状RNA hsa_circ_0018430在肺鳞状细胞癌(lung squamous cell carcinoma, LSCC)的表达水平与临床意义。

方法

2021年3月至2022年10月期间收集46例LSCC患者的肿瘤组织与血清样本。提取血清外泌体,通过透射电镜、NTA以及western blot对血清外泌体的形态与粒径分布进行了表征。利用实时荧光定量PCR(quantitative real-time PCR, qPCR)法检测血清外泌体hsa_circ_0018430相对表达水平,采用受试者工作特征(ROC)曲线并结合患者临床特征分析hsa_circ_0018430对LSCC的诊断,采用ELISA检测LSCC患者BICC1蛋白的表达。

结果

LSCC患者血清外泌体呈具有皮膜结构的球状,粒径分布在30~180 nm之间,血清外泌体hsa_circ_0018430表达水平分布为3.928(2.553~5.303)。ROC分析表明血清外泌体hsa_circ_0018430的AUC值为0.881(95%CI:0.809~0.952,P<0.001),灵敏度86.51%,特异性91.37%。血清外泌体hsa_circ_0018430表达水平与肺鳞癌患者TNM分期、淋巴结转移和血清CEA基线水平有关(P<0.05)。TCGA数据库分析表明LSCC患者组织中BICC1呈低表达(P<0.05),BICC1的表达水平与TNM分期和总生存期无显著相关性。ELISA检测LSCC患者癌组织中BICC1的表达水平相比于癌旁组织显著下调(P<0.05)。

结论

LSCC患者血清外泌体hsa_circ_0018430表达水平升高,与癌症进展指标相关,有望成为LSCC诊断与治疗评估的新型生物标志物。

Objective

To analyze the expression and clinical significance of serum exosomal circular RNA hsa_circ_0018430 in lung squamous cell carcinoma (LSCC).

Methods

From March 2020 to October 2022, tumor tissues and serum samples were collected from patients with LSCC. Serum exosomes were extracted, and the morphology and particle size distribution of serum exosomes were characterized by transmission electron microscopy, NTA, and western blot. Quantitative real-time PCR (qPCR) was used to detect the relative expression of hsa_circ_0018430. The receiver operating characteristic (ROC) curve and clinical significance of hsa_circ_0018430 in serum exosomes were used to analyze the efficacy of hsa_circ_0018430 in diagnosing LSCC. ELISA assays were used to detect the expression of BICC1 in LSCC.

Results

The relative expression level of serum exosomal hsa_circ_0018430 in LSCC patients was significantly higher than that in healthy controls [3.928 (2.553~5.303) vs. 1.823 (0.798~2.848), P<0.001], sensitivity 86.51%, specificity 91.37%. According to the ROC analysis, the AUC of hsa_circ_0018430 expression for distinguishing LSCC from healthy controls was 0.881 (95%CI: 0.809~0.952, P<0.001). The level of serum exosomal hsa_circ_0018430 was correlated with TNM stage, lymphatic metastasis and serum CEA level (P<0.05), but not with age, sex, tumor size, and smoking history (P>0.05). The TCGA database analysis showed the significant impaired BICC1 expression in LSCC patients (P<0.05), and there was no significant association between the expression level of BICC1 and TNM stage and overall survival (P>0.05). The expression level of BICC1 in cancer tissues of 46 LSCC patients was significantly down-regulated compared with that in adjacent tissues by ELISA assays (P<0.05).

Conclusion

The serum exosomal hsa_circ_0018430 expression level in LSCC patients is increased, which is expected to be the valuable new biomarkers for the diagnosis and treatment of LSCC.

图1 两组血清外泌体特征鉴定结果。注:A:透射电镜观察血清外泌体形态;B:纳米颗粒追踪分析;C: Western blotting法检测典型特征蛋白表达
表1 血清外泌体hsa_circ_0018430表达水平与LSCC临床病理特征[n(±s)]
图2 LSCC患者组织中BICC1的表达水平。注:A: TCGA数据库LUAD与LSCC患者组织BICC1表达水平(*P<0.05);B:不同TNM分期LSCC患者组织BICC1的表达水平;C: LSCC患者总体生存率;D: LSCC患者癌组织与癌旁
1
Osmani L, Askin F, Gabrielson E, et al. Current WHO guidelines and the critical role of immunohistochemical markers in the subclassification of non-small cell lung carcinoma (NSCLC): Moving from targeted therapy to immunotherapy[J]. Semin Cancer Biol, 2018, 52: 103-109.
2
白 莹,马 娟,吕 欣,等. 慢性阻塞性肺疾病合并肺癌临床特征分析[J/CD]. 中华肺部疾病杂志(电子版), 2021, 14(3): 265-271.
3
Coudray N, Ocampo PS, Sakellaropoulos T, et al. Classification and mutation prediction from non-small cell lung cancer histopathology images using deep learning[J]. Nat Med, 2018, 24: 1559-1567.
4
Lim SW, Ahn MJ. Current status of immune checkpoint inhibitors in treatment of non-small celllung cancer[J]. Korean J Intern Med, 2019, 34(1): 50- 59.
5
Shehzad A, Islam SU, Shahzad R, et al. Extracellular vesicles in cancer diagnostics and therapeutics[J]. Pharmacol Therapeut, 2021, 223: 107806.
6
Shehzad A, Islam SU, Shahzad R, et al. Extracellular vesicles in cancer diagnostics and therapeutics[J]. Pharmacol Therapeut, 2021: 107806.
7
Paskeh MDA, Entezari M, Mirzaei S, et al. Emerging role of exosomes in cancer progression and tumor microenvironment remodeling[J]. J Hematol Oncol, 2022, 15(1): 83.
8
Skalnikova HK, Bohuslavova B, Turnovcova K, et al. Isolation and Characterization of Small Extracellular Vesicles from Porcine Blood Plasma, Cerebrospinal Fluid, and Seminal Plasma[J]. Proteomes, 2019, 7(2): 17.
9
Logozzi M, Di Raimo R, Mizzoni D, et al. What we know on the potential use of exosomes for nanodelivery[J]. Semin Cancer Biol, 2022, 86(1): 13-25.
10
Stefanius K, Servage K, Orth K. Exosomes in cancer development[J]. Curr Opin Genet Dev, 2021, 66: 83-92.
11
Medeiros T, Myette RL, Almeida JR, et al. Extracellular Vesicles: Cell-Derived Biomarkers of Glomerular and Tubular Injury[J]. Cell Physiol Biochem, 2020, 54(1): 88-109.
12
Wang Y, Zhang H, Wang J, et al. Circular RNA expression profile of lung squamous cell carcinoma: identification of potential biomarkers and therapeutic targets[J]. Biosci Rep, 2020, 40(4): BSR20194512.
13
Salzman J, Chen RE, Olsen MN, et al. Cell-type specific features of circular RNA expression[J]. PLoS Genet, 2013, 9(9): e1003777.
14
Charlesworth A, Meijer HA, De Moor CH. Specificity factors in cytoplasmic polyadenylation[J]. Wiley Interdiscip Rev RNA, 2013, 4(4): 437-461.
15
Zhao R, Peng C, Song C, et al. BICC1 as a novel prognostic biomarker in gastric cancer correlating with immune infiltrates[J]. Int Immunopharmacol, 2020, 87: 106828.
16
Wang H, Guo Y, Mi N, et al. miR-101-3p and miR-199b-5p promote cell apoptosis in oral cancer by targeting BICC1[J]. Mol Cell Probes, 2020, 52: 101567.
17
Wankhede D. Evaluation of eighth AJCC TNM sage for lungcancer NSCLC: ameta-analysis[J]. Ann Surg Oncol, 2021, 28(1): 142-147.
18
Hessvik NP, Liorente A. Current knowledge on exosome biogenesis and release[J]. Cell Mol Life Sci, 2018, 75: 193-208.
19
Li X, Yang L, Chen LL. The Biogenesis, functions, and challenges of circular RNAs[J]. Mol Cell, 2018, 71: 428-442.
20
Cheng Z, Yu C, Cui S, et al. circTP63 functions as a ceRNA to promote lung squamous cell carcinoma progression by upregulating FOXM1[J]. Nat Commun, 2019, 10(1): 3200.
21
Zhang LX, Gao J, Long X, et al. The circular RNA circHMGB2 drives immunosuppression and anti-PD-1 resistance in lung adenocarcinomas and squamous cell carcinomas via the miR-181a-5p/CARM1 axis[J]. Mol Cancer, 2022, 21(1): 110.
22
Liang Y, Wang N, Zhang Y, et al. Self-restricted circular RNA circSOX2 suppressed the malignant progression in SOX2-amplified LUSC[J]. Cell Death Dis, 2022, 13(10): 873.
23
Paskeh MDA, Entezari M, Mirzaei S, et al. Emerging role of exosomes in cancer progression and tumor microenvironment remodeling[J]. J Hematol Oncol, 2022, 15(1): 83.
24
Medeiros T, Myette RL, Almeida JR, et al. Extracellular vesicles: Cell-derived biomarkers of glomerular and tubular injury[J]. Cell Physiol Biochem, 2020, 54(1): 88-109.
25
Stahl PD, Raposo G. Extracellular vesicles: Exosomes and microvesicles,integrators of homeostasis[J]. Physiology, 2019, 34(3): 169-177.
26
Perez-Boza J, Lion M, Struman I. Exploring the RNA landscape of endothelial exosomes[J]. RNA, 2018, 24: 423-435.
27
Santangelo L, Giurato G, Cicchini C, et al. The RNA-binding protein SYNCRIP is a component of the hepatocyte exosomal machinery controlling microRNA sorting [J]. Cell Rep, 2016, 17: 799-808.
28
Wei H, Chen Q, Lin L, et al. Regulation of exosome production and cargo sorting[J]. Int J Biol Sci, 2021, 17(1): 163-177.
29
Li X, Yang L, Chen LL. The Biogenesis, functions, and challenges of circular RNAs[J]. Mol Cell, 2018, 71(3): 428-442.
30
Wilusz JE. A 360° view of circular RNAs: From biogenesis to functions[J]. Wiley Interdiscip Rev RNA, 2018, 9(4): e1478.
31
Luo Y, Liu F, Ma J, et al. A novel epigenetic regulation of circFoxp1 on Foxp1 in colon cancer cells[J]. Cell Death Dis, 2020, 11(9): 782.
[1] 纪文鑫, 王茂, 邱春丽, 李尚鹏, 代引海. 血清外泌体circ PVT1与circ 0014606在三阴性乳腺癌中的表达及临床意义[J]. 中华普外科手术学杂志(电子版), 2023, 17(03): 267-271.
[2] 张博, 韩威, 郝少龙, 李泽乾, 纪智礼. 竞争内源性RNA在胰腺癌研究中的进展[J]. 中华普外科手术学杂志(电子版), 2023, 17(02): 213-216.
[3] 王邦郁, 陈晓鹏, 唐国军, 王佳妮. 尿液细胞外囊泡circRNA分类器对高级别前列腺癌诊断价值的初步研究[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(04): 339-342.
[4] 黄承路, 廖飞, 刘显平, 王志强. 血清外泌体Has_circ_0060937过度表达与NSCLC转移和不良预后的关系[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 490-494.
[5] 杨美, 简亿, 方莉, 余枝娟, 张建勇. 肺鳞癌合并鼻部弥漫大B细胞淋巴瘤一例[J]. 中华肺部疾病杂志(电子版), 2022, 15(06): 926-928.
[6] 黄朝旺, 韦雅琴, 许发琼, 徐康乔, 胡巧, 张静, 夏世金, 胡明冬. mmu_circ_0001033过表达慢病毒载体的构建与鉴定[J]. 中华肺部疾病杂志(电子版), 2022, 15(02): 141-145.
[7] 孙文思, 于皎皎, 林杉. circ_0000267靶向miR-198对急性淋巴细胞白血病细胞KOCL44增殖和凋亡的影响[J]. 中华细胞与干细胞杂志(电子版), 2022, 12(01): 19-25.
[8] 郭静, 齐卫红. circ_0000218通过靶向吸附miR-1182对宫颈癌HeLa细胞增殖、迁移和侵袭的影响[J]. 中华细胞与干细胞杂志(电子版), 2021, 11(02): 113-119.
[9] 王楚风, 蒋安. 原发性肝癌的分子诊断[J]. 中华肝脏外科手术学电子杂志, 2023, 12(05): 499-503.
[10] 魏英城, 霍励耘, 谭文亮, 陈新明, 陈亚进, 商昌珍. 环状RNA circRTN4IP1在肝细胞癌中的生物信息学分析及其与预后的关系[J]. 中华肝脏外科手术学电子杂志, 2021, 10(03): 331-336.
[11] 范博洋, 王宁, 张骞, 王贵玉. 结直肠癌转移调控的环状RNA分子机制研究进展[J]. 中华结直肠疾病电子杂志, 2023, 12(05): 426-430.
[12] 潘娟, 乔晞. 环状核糖核酸:糖尿病肾病治疗新靶点[J]. 中华肾病研究电子杂志, 2022, 11(01): 44-47.
[13] 方蕊, 宋旭东. 非编码核糖核酸与白内障相关的研究进展[J]. 中华眼科医学杂志(电子版), 2023, 13(02): 94-98.
[14] 李燕, 姚毅冰, 毛志远, 于海燕, 刘昕, 樊再雯. NCAPH在肺鳞癌中表达的临床意义及与免疫微环境浸润的关系[J]. 中华临床医师杂志(电子版), 2023, 17(04): 446-454.
[15] 邹春燕, 赵东强. 环状RNA在胃肠道间质瘤的作用及机制研究进展[J]. 中华胃肠内镜电子杂志, 2021, 08(04): 179-181.
阅读次数
全文


摘要