Journal of Shandong University (Health Sciences) ›› 2024, Vol. 62 ›› Issue (5): 79-88.doi: 10.6040/j.issn.1671-7554.0.2024.0134

• Clinical Medicine • Previous Articles    

Expression and diagnostic value of plasma exosomal miR-548k in esophageal squamous cell carcinoma

FENG Xumei1, SONG Xiangqing2, JI Guanhong2, ZHAO Xiaogang2, XIAO Zhaohua2   

  1. 1. Health Management Center, The Second Hospital of Shandong University, Jinan 250033, Shandong, China;
    2. Department of Thoracic Surgery, The Second Hospital of Shandong University, Jinan 250033, Shandong, China
  • Published:2024-05-29

Abstract: Objective To screen out the candidate plasma exosomal microRNAs(miRNAs)which play crucial role in esophageal squamous cell carcinoma(ESCC)occurrence and evaluate their potential in ESCC diagnosis. Methods A total of 55 ESCC patients who underwent surgical resection at The Second Hospital of Shandong University from March 2020 to June 2021 and 55 healthy volunteers were enrolled in this study. After identified by transmission electron microscopy(TEM), NanoSight tracking analysis(NTA)and Western blotting assays, RNA sequencing was performed to determine the miRNA profiles of plasma exosomes from 5 ESCC patients and 5 healthy control. Then, quantitative real-time PCR(qRT-PCR)was used to detect the expression level of differential exosomal miRNAs in the training and validation sets. Then, receiver operating characteristic(ROC)curve was conducted to evaluate their diagnostic value. Results Five miRNAs(miR-548k, miR-6516-5p, let-7b-3p, miR-3934-5p, miR-196a-5p)were significantly higher, and 8 miRNAs(miR-34c-5p, novel_167, miR-548u, miR-548ah-3p, miR-548p, miR-200a-5p, miR-200b-3p,miR-1228-5p)were obviously decreased in plasma exosomes of ESCC group than that of control group. Additionally, through the training cohort, we verified that miR-548k was significantly up-regulated in plasma exosomes of ESCC group(P<0.001). ROC curve analysis revealed that exosomal miR-548k exhibited higher accuracy than miR-34c-5p, miR-548u, miR-6516-5p in ESCC diagnosis, and the area under ROC curve(AUC)value was 0.918. Finally, through the validation cohort, we further confirmed that miR-548k was highly expressed in plasma exosomes of ESCC group(P<0.001), and plasma exosomal miR-548k could be used for ESCC diagnosis(AUC=0.889). Conclusion MiR-548k is significantly up-regulated in plasma exosomes of ESCC patients and plasma exosomal miR-548k has high clinical diagnostic value for ESCC.

Key words: Esophageal squamous cell carcinoma, Plasma exosomes, Diagnosis, Biomarker, miR-548k

CLC Number: 

  • R735.1
[1] Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249.
[2] Yang S, Lin S, Li N, et al. Burden, trends, and risk factors of esophageal cancer in China from 1990 to 2017: an up-to-date overview and comparison with those in Japan and South Korea[J]. J Hematol Oncol, 2020, 13(1): 146.
[3] Visaggi P, Barberio B, Ghisa M, et al. Modern diagnosis of early esophageal cancer: from blood biomarkers to advanced endoscopy and artificial intelligence[J]. Cancers(Basel), 2021, 13(13): 3162. doi:10.3390/cancers13133162.
[4] Codipilly DC, Qin Y, Dawsey SM, et al. Screening for esophageal squamous cell carcinoma: recent advances[J]. Gastrointest Endosc, 2018, 88(3): 413-426.
[5] Ju M, Ge X, Di X, et al. Diagnostic, prognostic, and recurrence monitoring value of plasma CYFRA21-1 and NSE levels in patients with esophageal squamous cell carcinoma[J]. Front Oncol, 2021, 11: 789312. doi:10.3389/fonc.2021.789312.
[6] Mou X, Peng ZL, Yin T, et al. Non-endoscopic screening for esophageal squamous cell carcinoma:recent advances[J]. J Gastrointest Cancer, 2023. doi:10.1007/s12029-023-00980-x.
[7] 宋颂, 雷林, 张瑞, 等. 食管癌筛查的研究进展[J]. 中华肿瘤防治杂志, 2022, 29(7): 451-455. SONG Song, LEI Lin, ZHANG Rui, et al. Research progress on screening for esophageal cancer[J]. Chinese Journal of Cancer Prevention and Treatment, 2022, 29(7): 451-455.
[8] 刘宇英, 魏君丽, 江柔, 等. 食管癌的流行病学及筛查研究进展[J]. 中华疾病控制杂志, 2022, 26(7): 839-844. LIU Yuying, WEI Junli, JIANG Rou, et al. Research progress on the epidemiology and screening of esophageal cancer[J]. Chinese Journal of Disease Control and Prevention, 2022, 26(7): 839-844.
[9] 凌媛媛, 于文俊, 乔永霞. 液体活检对食管癌诊疗和预后的价值[J]. 中国细胞生物学学报, 2023, 45(12): 1896-1907. LING Yuanyuan, YU Wenjun, QIAO Yongxia. Diagnostic and prognostic values of liquid biopsy in esophageal cancer[J]. Chinese Journal of Cell Biology, 2023, 45(12): 1896-1907.
[10] Liu J, Ren L, Li S, et al. The biology, function, and applications of exosomes in cancer[J]. Acta Pharm Sin B, 2021, 11(9): 2783-2797.
[11] Pegtel DM, Gould SJ. Exosomes[J]. Annu Rev Biochem, 2019, 88: 487-514.doi:10.1146/annurev-biochem-013118-111902.
[12] Shang RF, Lee S, Senavirathne G, et al. MicroRNAs in action: biogenesis, function and regulation[J]. Nat Rev Genet, 2023, 24: 816-833. doi:10.1038/s41576-023-00611-y.
[13] Sun Z, Sun Z, Shi K, et al. Effect of exosomal miRNA on cancer biology and clinical applications[J]. Mol Cancer, 2018, 17(1): 147.
[14] Du Y, Wu L, Wang L, et al. Extracellular vesicles in cardiovascular diseases: from pathophysiology to diagnosis and therapy[J]. Cytokine Growth Factor Rev, 2023, 74: 40-55. doi:10.1016/j.cytogfr.2023.09.006.
[15] 郑清月, 赵秋红, 渠香云, 等. 血清外泌体miR-205-5p/miR-152-5p 对早期非小细胞肺癌的诊断价值[J]. 山东大学学报(医学版), 2019, 57(10): 101-106. ZHENG Qingyue, ZHAO Qiuhong, QU Xiangyun, et al. Diagnosis value of serum exosome miR-205-5p/miR-152-5p on early non-small cell lung cancer[J]. Journal of Shandong University(Health Sciences), 2019, 57(10): 101-106.
[16] Preethi KA, Selvakumar SC, Ross K, et al. Liquid biopsy: exosomal microRNAs as novel diagnostic and prognostic biomarkers in cancer[J]. Mol Cancer, 2022, 21(1): 54. doi:10.1186/s12943-022-01525-9.
[17] Xiao Z, Feng X, Zhou Y, et al. Exosomal miR-10527-5p inhibits migration, invasion, lymphangiogenesis and lymphatic metastasis by affecting Wnt/β-catenin signaling via Rab10 in esophageal squamous cell carcinoma[J]. Int J Nanomedicine, 2023, 18: 95-114. doi:10.2147/ijn.s391173.
[18] Zhou L, Wang W, Wang F, et al. Plasma-derived exosomal miR-15a-5p as a promising diagnostic biomarker for early detection of endometrial carcinoma[J]. Mol Cancer, 2021, 20(1): 57. doi:10.1186/s12943-021-01352-4.
[19] Chandrashekar DS, Karthikeyan SK, Korla PK, et al. UALCAN: an update to the integrated cancer data analysis platform[J]. Neoplasia, 2022, 25: 18-27. doi:10.1016/j.neo.2022.01.001.
[20] Lánczky A, Györffy B. Web-based survival analysis tool tailored for medical research(KMplot): development and implementation[J]. J Med Internet Res, 2021, 23(7): e27633. doi:10.2196/27633.
[21] Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes[J]. Science, 2020, 367(6478): eaau6977.
[22] Boriachek K, Islam MN, Möller A, et al. Biological functions and current advances in isolation and detection strategies for exosome nanovesicles[J]. Small, 2018, 14(6). doi:10.1002/smll.201702153.
[23] 王传新. 外泌体生物标志物与肿瘤发生发展的研究进展[J]. 山东大学学报(医学版), 2018, 56(10): 18-23. WANG Chuanxin. Research progress of exosomes biomarkers in tumor development[J]. Journal of Shandong University(Health Sciences), 2018, 56(10): 18-23.
[24] Yu W, Hurley J, Roberts D, et al. Exosome-based liquid biopsies in cancer: opportunities and challenges[J]. Ann Oncol, 2021, 32(4): 466-477.
[25] Patel G, Agnihotri TG, Gitte M, et al. Exosomes: a potential diagnostic and treatment modality in the quest for counteracting cancer[J]. Cell Oncol, 2023, 46(5): 1159-1179.
[26] 金玮娜,陈蒙蒙,彭天娇,等. 食管癌相关外泌体miRNA的研究进展[J]. 食管疾病, 2022, 4(3): 193-197. JIN Weina, CHEN Mengmeng, PENG Tianjiao, et al. Progress in esophageal cancer-related exosomal miRNA[J]. Journal of Esophageal Diseases, 2022, 4(3): 193-197.
[27] Jing Z, Chen K, Gong L. The significance of exosomes in pathogenesis, diagnosis, and treatment of esophageal cancer[J]. Int J Nanomedicine, 2021, 16: 6115-6127. doi:10.2147/ijn.s321555.
[28] Yan S, Du L, Jiang X, et al. Evaluation of serum exosomal lncRNAs as diagnostic and prognostic biomarkers for esophageal squamous cell carcinoma[J]. Cancer Manag Res, 2020, 12: 9753-9763. doi:10.2147/cmar.s250971.
[29] Zhang W, Hong R, Li L, et al. The chromosome 11q13.3 amplification associated lymph node metastasis is driven by miR-548k through modulating tumor microenvironment[J]. Mol Cancer, 2018, 17(1): 125. doi:10.1186/s12943-018-0871-4.
[30] Chen Z, Lin J, Wu S, et al. Up-regulated miR-548k promotes esophageal squamous cell carcinoma progression via targeting long noncoding RNA-LET[J]. Exp Cell Res, 2018, 362(1): 90-101.
[31] Lin J, Chen Z, Wu S, et al. An NF90/long noncoding RNA-LET/miR-548k feedback amplification loop controls esophageal squamous cell carcinoma progression[J]. J Cancer, 2019, 10(21): 5139-5152.
[32] Yadollahi-Farsani M, Amini-Farsani Z, Moayedi F, et al. MiR-548k suppresses apoptosis in breast cancer cells by affecting PTEN/PI3K/AKT signaling pathway[J]. IUBMB Life, 2023, 75(2): 97-116.
[33] Liu Z, Huang Y, Han Z, et al. Exosome-mediated miR-25/miR-203 as a potential biomarker for esophageal squamous cell carcinoma: improving early diagnosis and revealing malignancy[J]. Transl Cancer Res, 2021, 10(12): 5174-5182.
[34] Kim S, Kim GH, Park SJ, et al. Exosomal microRNA analyses in esophageal squamous cell carcinoma cell lines[J]. J Clin Med, 2022, 11(15): 4426. doi:10.3390/jcm11154426.
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