Hudcova Kristyna, Raudenska Martina, Gumulec Jaromir, Binkova Hana, Horakova Zuzana, Kostrica Rom, Babula Petr, Adam Vojtech, Masarik Michal
Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00, Brno, Czech Republic.
Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00, Brno, Czech Republic.
Tumour Biol. 2016 Sep;37(9):12627-12633. doi: 10.1007/s13277-016-5147-2. Epub 2016 Jul 20.
Altered expression of microRNAs (miRNAs) has been shown in many types of malignancies including the head and neck squamous cell carcinoma (HNSCC). Although there are many new and innovative approaches in the treatment of HNSCC, a clear marker of this disease is still missing. Three candidate miRNAs (miR-29c-3p, miR-200b-5p and miR-375-3p) were studied in connection with HNSCC using quantitative real-time PCR expression levels in 42 tissue samples of HNSCC patients and histologically normal tumour-adjacent tissue samples of these patients. Primary HNSCC carcinoma tissues can be distinguished from histologically normal-matched noncancerous tumour-adjacent tissues based on hsa-miR-375-3p expression (sensitivity 87.5 %, specificity 65 %). Additionally, a significant decrease of hsa-miR-200b-5p expression was revealed in tumour-adjacent tissue samples of patients with node positivity. Lower expression of hsa-miR-200b-5p and hsa-miR-29c-3p in HNSCC tumour tissue was associated with higher tumour grade. Consequently, survival analysis was performed. Lower expression of hsa-miR-29c-3p in tumour-adjacent tissue was associated with worse overall and disease-specific survivals. Lower expression of miR-29c-3p in tumourous tissue was associated with worse relapse-free survival. hsa-miR-375-3p seems to be a relatively promising diagnostic marker in HNSCC but is not suitable for prognosis of patients. Furthermore, this study highlighted the importance of histologically normal tumour-adjacent tissue in HNSCC progress (significant decrease of hsa-miR-200b-5p expression in tumour-adjacent tissue of patients with node positivity and low expression of hsa-miR-29c-3p in HNSCC tumour-adjacent tissue associated with worse prognosis).
微小RNA(miRNA)表达的改变已在包括头颈部鳞状细胞癌(HNSCC)在内的多种恶性肿瘤中被发现。尽管在HNSCC的治疗方面有许多新的创新方法,但这种疾病仍缺乏明确的标志物。使用定量实时PCR检测了42例HNSCC患者的组织样本以及这些患者组织学正常的肿瘤邻近组织样本中,三种候选miRNA(miR-29c-3p、miR-200b-5p和miR-375-3p)与HNSCC的关系。基于hsa-miR-375-3p的表达,原发性HNSCC癌组织可与组织学正常的配对非癌性肿瘤邻近组织区分开来(敏感性87.5%,特异性65%)。此外,在淋巴结阳性患者的肿瘤邻近组织样本中,hsa-miR-200b-5p的表达显著降低。HNSCC肿瘤组织中hsa-miR-200b-5p和hsa-miR-29c-3p的低表达与更高的肿瘤分级相关。因此,进行了生存分析。肿瘤邻近组织中hsa-miR-29c-3p的低表达与总体生存率和疾病特异性生存率较差相关。肿瘤组织中miR-29c-3p的低表达与无复发生存率较差相关。hsa-miR-375-3p似乎是HNSCC中一个相对有前景的诊断标志物,但不适合用于患者的预后评估。此外,本研究强调了组织学正常的肿瘤邻近组织在HNSCC进展中的重要性(淋巴结阳性患者的肿瘤邻近组织中hsa-miR-200b-5p表达显著降低,HNSCC肿瘤邻近组织中hsa-miR-29c-3p低表达与预后较差相关)。