Identification of a novel microRNA profile including miR-106b, miR-17, miR-20b, miR-18a and miR-93 in the metastasis of nasopharyngeal carcinoma.
鉴定一种新的 microRNA 谱，包括 miR-106b 、 miR-17 、 miR-20b 、 miR-18a 和鼻咽癌转移中的 miR-93。
- 作者列表："Zhou W","Chang A","Zhao H","Ye H","Li D","Zhuo X
BACKGROUND:Metastasis often leads to poor prognosis in nasopharyngeal carcinoma (NPC) patients. Evidence has indicated the important roles of microRNA (miRNA) in cancer metastasis. The aim of this study was to identify and verify the key miRNAs that might be involved in the development of NPC metastasis. METHODS:Microarray data were obtained and analyzed to screen the differentially expressed miRNAs (DEMs) between NPC tissues with metastasis and those without metastasis. The target genes of the DEMs were predicted and their functions were annotated. Then, candidate hub genes were screened out through protein-protein interaction analysis, and the key miRNAs were identified. Afterwards, the expression levels of the key miRNAs were assessed by qRT-PCR based on an in vitro model. RESULTS:A total of 22 DEMs were screened out, and 616 target genes were predicted. Gene Ontology (GO) and pathway enrichment analysis showed that the target genes may be enriched in a diversity of GO terms and signaling pathways. Among them, eleven hub genes were identified, such as PTEN, KAT2B, CCND1, STAT3, and MAP3K5. Moreover, a five-miRNA profile (miR-106b, miR-17, miR-20b, miR-18a and miR-93) was identified and their expression levels were tested to be up-regulated in high-metastatic NPC cells relative to low-metastatic ones. CONCLUSION:The present study revealed that five miRNAs (miR-106b, miR-17, miR-20b, miR-18a and miR-93) and several hub genes such as PTEN, KAT2B, CCND1, STAT3, and MAP3K5, might play critical roles in the development of NPC metastasis. Future investigations are needed to confirm the results.
背景: 在鼻咽癌 (NPC) 患者中，转移常导致不良预后。有证据表明 microRNA (miRNA) 在癌症转移中的重要作用。本研究的目的是鉴定和验证可能参与鼻咽癌转移发展的关键 miRNAs。 方法: 获得基因芯片数据并进行分析，筛选有转移和无转移的 NPC 组织之间的差异表达 miRNAs (DEMs)。预测了 DEMs 的靶基因，并对其功能进行了注释。然后，通过蛋白质-蛋白质相互作用分析筛选出候选的 hub 基因，并鉴定出关键的 miRNAs。随后，基于体外模型通过 qRT-PCR 评估关键 miRNAs 的表达水平。 结果: 共筛选出 22 个 DEMs，预测出 616 个目的基因。基因本体论 (Gene Ontology，GO) 和 pathway 富集分析表明，目的基因可能富集在 GO 术语和信号通路的多样性中。其中，确定了 11 个 hub 基因，如 PTEN 、 KAT2B 、 CCND1 、 STAT3 和 MAP3K5。此外，五个 miRNA 谱 (miR-106b 、 miR-17 、 miR-20b 、 miR-18a 和 miR-93) 进行了鉴定，并检测了它们的表达水平在高转移 NPC 细胞中相对于低转移细胞的表达水平上调。 结论: 本研究揭示了 5 个 miRNAs (miR-106b 、 miR-17 、 miR-20b 、 miR-18a 和 miR-93) 和几个中心基因，如 PTEN 、 KAT2B 、 CCND1 、 STAT3 和 MAP3K5, 可能在鼻咽癌转移的发展中起关键作用。需要未来的调查来确认结果。
METHODS:INTRODUCTION:Human papillomavirus (HPV) is the most common sexually transmitted infection and is associated with several types of cancer. The number of cases of HPV-associated head and neck squamous cell carcinomas (HNSCCs), especially oropharyngeal carcinomas, has increased significantly in recent years despite decreased tobacco smoking rates. Currently, no data concerning the risk factors and prevalence of HPV in HNSCC patients in all regions of Brazil are available, making it difficult to promote advances in this field of public health. Therefore, our goal is to determine the impact of infection by HPV, including HPVs with different genotypes, on head and neck cancer and the risk factors associated with the development of head and neck cancer in all regions of Brazil. METHODS AND ANALYSIS:This is a case-control study that will include 622 patients and 622 controls from all regions of Brazil. A questionnaire will be applied to gather information on sociodemographic, behavioural and health factors. Oral, cervical or penile/scrotal, and anal specimens and serum samples will be collected from all participants. Formalin-fixed paraffin-embedded tissue from tumour biopsies will be analysed only in the case group. Molecular and serological analyses will be performed to evaluate the presence and role of HPV in the development of head and neck cancer. ETHICS AND DISSEMINATION:This project was approved by the research ethical committee of the proposing institution (Hospital Moinhos de Vento, number 2.852.060). Ethical approval from the collaborators is currently under evaluation and is not yet complete. The results of this study will be presented at meetings with the Brazilian Ministry of Health through technical reports and to the scientific community at national and international events, with subsequent publication of scientific articles.
METHODS:BACKGROUND:Factors related to head and neck cancer and the treatment of the disease can affect quality of life. The aim of this study was to determine factors associated with the severity of impact on oral health-related quality of life (OHRQoL) in survivors of head and neck cancer using a multivariate analysis. METHODS:This cross-sectional study evaluated 90 volunteers who had completed radiotherapy at least 3 months earlier. OHRQoL was assessed using oral health impact profile (OHIP-14) and the data were analyzed using robust variance poisson regression models. RESULTS:The mean total OHIP-14 score was 23.98 ± 12.55. Patients with hyposalivation had 56% higher (worse) mean OHIP-14 total scores (CI:1.11-2.18) and patients with advanced stage tumors had 31% higher mean OHIP-14 total scores (CI:1.03-1.66) in multivariate analyses. CONCLUSION:OHRQoL of survivors of head and neck cancer experienced a negative impact following radiotherapy. The impact was associated with hyposalivation and advanced stage tumors.
METHODS:BACKGROUND:To immunohistochemically evaluate the association between the presence of cancer-associated fibroblasts (CAFs) and the tumour expression of podoplanin (PDPN) in head and neck squamous cell carcinoma (HNSCC) and their association with clinicopathological variables. MATERIAL AND METHODS:A tissue microarray (TMA) with biopsy sections from patients diagnosed with HNSCC was stained with antibodies against the CAFs marker, α-smooth muscle actin (α-SMA), and PDPN. We subsequently evaluated their expression to determine the association between them and with clinicopathological variables including age, primary tumour site, TNM stage, and tumour differentiation grade. RESULTS:Positive reaction to α-SMA was observed in the tumour stroma, revealing spindle-shaped cells compatible with CAFs, which showed a high expression in 62% of cases and a significant association with laryngeal carcinomas, advanced clinical stages, and lower tumour differentiation (P ≤ 0.05). PDPN staining on tumour cells showed low expression in 72% of cases, and it was not associated with any clinicopathological variable or with the presence of CAFs. CONCLUSIONS:The presence of CAFs in the tumour stroma is related to an aggressive phenotype and could increase as the disease progresses, although based on our findings, it would have no relationship, at least directly, with the expression of PDPN.