循环 miR-10b、可溶性尿激酶型纤溶酶原激活物受体和纤溶酶原激活物抑制剂-1 可预测非小细胞肺癌的进展和治疗反应。

IF 2.2 4区 医学 Q3 ONCOLOGY Cancer Biomarkers Pub Date : 2024-01-01 DOI:10.3233/CBM-220222
Lyana Setiawan, Rahajuningsih Setiabudy, Siti Boedina Kresno, Noorwati Sutandyo, Elisna Syahruddin, Frederica Jovianti, Siti Nadliroh, Sofia Mubarika, Rianto Setiabudy, Nurjati C Siregar
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引用次数: 0

摘要

背景:尽管肺癌治疗取得了进展,但大多数肺癌都是在晚期确诊的。microRNA10b(miR-10b)的表达以及可溶性尿激酶型纤溶酶原激活物受体(suPAR)和纤溶酶原激活物抑制剂 1(PAI-1)所反映的纤溶活性是很有希望的候选生物标记物:目的:评估晚期非小细胞肺癌(NSCLC)患者体内 miR-10b 的表达、血清中 suPAR 和 PAI-1 的水平及其与病情进展、治疗反应和预后的相关性:本前瞻性队列和生存研究在达迈斯国立癌症医院进行,纳入了2015年3月至2016年9月期间确诊的晚期NSCLC患者。采用 qRT-PCR 对 miR-10b 的表达进行量化。使用ELISA检测了suPAR和PAI-1的水平。治疗反应采用 RECIST 1.1 标准进行评估。对患者进行随访,直至死亡或治疗后至少 1 年:结果:在入组的40名患者中,25人完成了至少4个周期的化疗,15人在治疗期间死亡。miR-10b绝对表达量⩾ 592 145拷贝/μL或miR-10b折叠变化⩾ 0.066是疾病进展和治疗反应差的保护因素,而suPAR水平⩾ 4 237 pg/mL是疾病进展和反应差的危险因素。PAI-1水平大于4.6纳克/毫升是不良反应的保护因素。多变量分析表明,suPAR 是导致疾病进展和反应不佳的危险因素。
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Circulating miR-10b, soluble urokinase-type plasminogen activator receptor, and plasminogen activator inhibitor-1 as predictors of non-small cell lung cancer progression and treatment response.

Background: Despite advances in lung cancer treatment, most lung cancers are diagnosed at an advanced stage. Expression of microRNA10b (miR-10b) and fibrinolytic activity, as reflected by soluble urokinase-type plasminogen activator receptor (suPAR) and plasminogen activator inhibitor 1 (PAI-1), are promising biomarker candidates.

Objective: To assess the expression of miR-10b, and serum levels of suPAR and PAI-1 in advanced stage non-small cell lung cancer (NSCLC) patients, and their correlation with progression, treatment response and prognosis.

Methods: The present prospective cohort and survival study was conducted at Dharmais National Cancer Hospital and included advanced stage NSCLC patients diagnosed between March 2015 and September 2016. Expression of miR-10b was quantified using qRT-PCR. Levels of suPAR and PAI-1 were assayed using ELISA. Treatment response was evaluated using the RECIST 1.1 criteria. Patients were followed up until death or at least 1 year after treatment.

Results: Among the 40 patients enrolled, 25 completed at least four cycles of chemotherapy and 15 patients died during treatment. Absolute miR-10b expression ⩾ 592,145 copies/μL or miR-10b fold change ⩾ 0.066 were protective for progressive disease and poor treatment response, whereas suPAR levels ⩾ 4,237 pg/mL was a risk factor for progressive disease and poor response. PAI-1 levels > 4.6 ng/mL was a protective factor for poor response. Multivariate analysis revealed suPAR as an independent risk factor for progression (ORa⁢d⁢j, 13.265; 95% confidence intervals (CI), 2.26577.701; P= 0.006) and poor response (ORa⁢d⁢j, 15.609; 95% CI, 2.221-109.704; P= 0.006), whereas PAI-1 was an independent protective factor of poor response (ORa⁢d⁢j, 0.127; 95% CI, 0.019-0.843; P= 0.033).

Conclusions: Since miR-10b cannot be used as an independent risk factor for NSCLC progression and treatment response, we developed a model to predict progression using suPAR levels and treatment response using suPAR and PAI-1 levels. Further studies are needed to validate this model.

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来源期刊
Cancer Biomarkers
Cancer Biomarkers ONCOLOGY-
CiteScore
5.20
自引率
3.20%
发文量
195
审稿时长
3 months
期刊介绍: Concentrating on molecular biomarkers in cancer research, Cancer Biomarkers publishes original research findings (and reviews solicited by the editor) on the subject of the identification of markers associated with the disease processes whether or not they are an integral part of the pathological lesion. The disease markers may include, but are not limited to, genomic, epigenomic, proteomics, cellular and morphologic, and genetic factors predisposing to the disease or indicating the occurrence of the disease. Manuscripts on these factors or biomarkers, either in altered forms, abnormal concentrations or with abnormal tissue distribution leading to disease causation will be accepted.
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