Identification of exosomal microRNA panel as diagnostic and prognostic biomarker for small cell lung cancer

被引：34

作者：

Kim, Dong Ha ^{[1
]}

Park, Hyojeong ^{[2
]}

Choi, Yun Jung ^{[1
]}

Im, Kyungtaek ^{[1
]}

Lee, Chae Won ^{[2
]}

Kim, Da-Som ^{[2
]}

Pack, Chan-Gi ^{[3
]}

Kim, Hyun-Yi ^{[6
]}

Choi, Chang-Min ^{[4
,5
]}

Lee, Jae Cheol ^{[5
]}

Ji, Wonjun ^{[4
]}

Rho, Jin Kyung ^{[3
]}

机构：

[1] Asan Inst Life Sci, Seoul 05505, South Korea

[2] AMIST, Dept Biomed Sci, Seoul 05505, South Korea

[3] Univ Ulsan, Coll Med, Dept Convergence Med, 88 Olymp Ro 43 Gil, Seoul 05505, South Korea

[4] Univ Ulsan, Dept Pulm Crit & Care Med, Coll Med, 88 Olymp Ro 43 Gil, Seoul 05505, South Korea

[5] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul 05505, South Korea

[6] NGeneS Inc, ., Asan, Gyeonggi Do, South Korea

来源：

BIOMARKER RESEARCH | 2023年 / 11卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

Exosome; Exosomal miRNA; Diagnosis; Prognosis; SCLC; MICROVESICLES; RNA; METASTASIS; MEMBRANE; RELEASE; MIRNAS; ROC;

D O I：

10.1186/s40364-023-00517-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BackgroundSmall cell lung cancer (SCLC) has an exceptionally poor prognosis; as most of the cases are initially diagnosed as extensive disease with hematogenous metastasis. Therefore, the early diagnosis of SCLC is very important and may improve its prognosis.MethodsTo investigate the feasibility of early diagnosis of SCLC, we examined exosomal microRNAs (miRNAs) present in serum obtained from patients with SCLC. First, exosomes were isolated in serum from patients with SCLC and healthy individuals and were characterized using particle size and protein markers. Additionally, miRNA array was performed to define SCLC-specific exosomal miRNAs. Second, the obtained miRNAs were further validated employing a large cohort. Finally, the ability to diagnose SCLC was estimated by area under the curve (AUC), and intracellular mRNA change patterns were verified through validated miRNAs.ResultsFrom the miRNA array results, we selected 51-miRNAs based on p-values and top 10 differentially expressed genes, and 25-miRNAs were validated using quantitative reverse transcription-polymerase chain reaction. The 25-miRNAs were further validated employing a large cohort. Among them, 7-miRNAs showed significant differences. Furthermore, 6-miRNAs (miR-3565, miR-3124-5p, miR-200b-3p, miR-6515, miR-3126-3p and miR-9-5p) were up-regulated and 1-miRNA (miR-92b-5p) was down-regulated. The AUC value of each miRNA sets between 0.64 and 0.76, however the combined application of 3-miRNAs (miR-200b-3p, miR-3124-5p and miR-92b-5p) remarkably improved the diagnostic value (AUC = 0.93). Gene ontology analysis revealed that the 3-miRNA panel is linked to various oncogene pathways and nervous system development. When the 3-miRNAs were introduced to cells, the resulting changes in total mRNA expression strongly indicated the presence of lung diseases, including lung cancer. In addition, the 3-miRNA panel was significantly associated with a poorer prognosis, although individual miRNAs have not been validated as prognostic markers.ConclusionOur study identified SCLC-specific exosomal miRNAs, and the 3-miRNAs panel (miR-200b-3p, miR-3124-5p and miR-92b-5p) may serve as a diagnostic and prognostic marker for SCLC.

引用

页数：14

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