MicroRNA-15a tissue expression is a prognostic marker for survival in patients with clear cell renal cell carcinoma

被引:10
作者
Mytsyk, Yulian [1 ]
Borys, Yuriy [1 ]
Tumanovska, Lesia [2 ]
Stroy, Dmytro [2 ]
Kucher, Askold [3 ]
Gazdikova, Katarina [4 ,5 ]
Rodrigo, Luis [6 ,7 ]
Kruzliak, Peter [8 ,9 ,10 ]
Prosecky, Robert [8 ]
Urdzik, Peter [11 ,12 ]
Dosenko, Victor [2 ]
机构
[1] Danylo Halytsky Lviv Natl Med Univ, Dept Urol, Pekarska Str 69, Lvov, Ukraine
[2] Natl Acad Sci, Bogomoletz Inst Physiol, Gen & Mol Pathophysiol Dept, Kiev, Ukraine
[3] Danylo Halytsky Lviv Natl Med Univ, Dept Radiol, Lvov, Ukraine
[4] Slovak Med Univ, Fac Nursing & Profess Hlth Studies, Dept Nutr, Limbova 12, Bratislava 83303, Slovakia
[5] Slovak Med Univ, Fac Med, Dept Gen Med, Bratislava, Slovakia
[6] Univ Oviedo, Fac Med, Oviedo, Spain
[7] Cent Univ Hosp Asturias HUCA, Oviedo, Spain
[8] Bros Mercy Hosp, Dept Internal Med, Polni 3, Brno 63900, Czech Republic
[9] Masaryk Univ, Fac Med, Dept Surg 2, Brno, Czech Republic
[10] St Annes Univ Hosp, Brno, Czech Republic
[11] Pavol Jozef Safarik Univ, Fac Med, Dept Gynaecol & Obstet, Tr SNP 1, Kosice 04001, Slovakia
[12] Louis Pasteur Univ Hosp, Tr SNP 1, Kosice 04001, Slovakia
关键词
Cancer; Renal cell carcinoma; Clear cell; miRNA-15a; MicroRNA-15a; Biomarker; Genetic; Prediction; Prognosis; Survival; DOWN-REGULATION; CANCER INCIDENCE; PROLIFERATION; SYSTEM; ALPHA; MODEL; 15A;
D O I
10.1007/s10238-019-00574-7
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
None of the currently investigated molecular markers demonstrated sufficient accuracy in prognostication of the renal cell carcinoma (RCC) oncologic outcomes; thus, none of them has been recommended for the application in the routine clinical practice. The role of miR-15a as a potential prognostic marker for RCC is still not unveiled. The aim of our study was to assess the expression of miR-15a in tumor tissues of the patients with RCC and to evaluate the possibility of its usage as a prognostic molecular biomarker of this disease. The retrospective included 64 adult patients with clear cell RCC (ccRCC) in whom radical or partial nephrectomy was conducted. After deparaffinization of formalin-fixed paraffin-embedded (FFPE) ccRCC specimens, the tissue expression of miR-15a was measured using the reverse transcription and quantitative polymerase chain reaction in the real time. For the reference, the expression of miR-15a was estimated in 15 FFPE tissue specimens of the normal renal parenchyma. Survival analysis involved all cases of non-metastatic RCCs (n = 57). Five-year cancer-specific survival (CSS) was estimated by means of the Kaplan-Meier method and was calculated from the date of surgery to the date of death. Patients with the RCC were characterized by significantly upregulated tumor tissue mean levels of miR-15a compared to the healthy controls: 0.10 +/- 2.62 relative units (RU) versus 4.84E - 03 +/- 3.11E - 03 RU (p < 0.001). Overexpression of miR-15a was strongly associated with poor histologic prognostic features of ccRCC. Poorly differentiated tumors tend to have more pronounced upregulation of miR-15a compared to highly differentiated lesions: Mean expression values were 4.57 +/- 3.19 RU for Fuhrman grade 4 versus 0.02 +/- 0.01 RU for Fuhrman grade 1 (p < 0.001). The metastatic involvement of the regional lymphatic nodules (N +) was associated with significantly upregulated miRNA-15a in comparison with N - cases: Mean expression values were 4.92 +/- 2.80 RU versus 1.10 +/- 2.29 RU, respectively (p < 0.001). In patients with miR-15a expression in RCC tissues <= 0.10 RU, mean 5-year CSS was significantly longer compared to patients with expression levels above this threshold: 92.31% (mean duration of survival-59.88 +/- 0.12 months) versus 54.8% (mean duration of survival-49.74 +/- 2.16 months), respectively (p < 0.001). The tissue expression of miR-15a could be used as a potential prognostic molecular biomarker for conventional RCC.
引用
收藏
页码:515 / 524
页数:10
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