Expression level and prospective mechanism of miRNA-99a-3p in head and neck squamous cell carcinoma based on miRNA-chip and miRNA-sequencing data in 1, 167 cases

2019 ◽  
Vol 215 (5) ◽  
pp. 963-976 ◽  
Author(s):  
Gan-Guan Wei ◽  
Wan-Ping Guo ◽  
Zheng-Yi Tang ◽  
Sheng-Hua Li ◽  
Hua-Yu Wu ◽  
...  
BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yusheng Huang ◽  
Zhiguo Liu ◽  
Limei Zhong ◽  
Yi Wen ◽  
Qixiang Ye ◽  
...  

Abstract Background Head and neck squamous cell carcinoma (HNSCC) is a fatal malignancy owing to the lack of effective tools to predict overall survival (OS). MicroRNAs (miRNAs) play an important role in HNSCC occurrence, development, invasion and metastasis, significantly affecting the OS of patients. Thus, the construction of miRNA-based risk signatures and nomograms is desirable to predict the OS of patients with HNSCC. Accordingly, in the present study, miRNA sequencing data of 71 HNSCC and 13 normal samples downloaded from The Cancer Genome Atlas (TCGA) were screened to identify differentially expressed miRNAs (DEMs) between HNSCC patients and normal controls. Based on the exclusion criteria, the clinical information and miRNA sequencing data of 67 HNSCC samples were selected and used to establish a miRNA-based signature and a prognostic nomogram. Forty-three HNSCC samples were assigned to an internal validation cohort for verifying the credibility and accuracy of the primary cohort. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore the functions of 11 miRNA target genes. Results In total, 11 DEMs were successfully identified. An 11-miRNA risk signature and a prognostic nomogram were constructed based on the expression levels of these 11 DEMs and clinical information. The signature and nomogram were further validated by calculating the C-index, area under the curve (AUC) in receiver-operating characteristic curve analysis, and calibration curves, which revealed their promising performance. The results of the internal validation cohort shown the reliable predictive accuracy both of the miRNA-based signature and the prognostic nomogram. GO and KEGG analyses revealed that a mass of signal pathways participated in HNSCC proliferation and metastasis. Conclusion Overall, we constructed an 11-miRNA-based signature and a prognostic nomogram with excellent accuracy for predicting the OS of patients with HNSCC.


2021 ◽  
Author(s):  
Jian Guan ◽  
Jinru Weng ◽  
Qiaosheng Ren ◽  
Chunbin Zhang ◽  
Liantao Hu ◽  
...  

CXCL3 plays extensive roles in tumorigenesis in various types of human cancers through its roles in tumor cell differentiation, invasion, and migration. However, the mechanisms of CXCL3 in head and neck squamous cell carcinoma (HNSCC) remains unclear. In our study, multiple databases were used to explore the expression level, prognostic value, and related mechanisms of CXCL3 in human HNSCC through bioinformatic methods. We also performed further experiments in vivo and in vitro to evaluate the expression of CXCL3 in a human head and neck tissue microarray and the underlying effect mechanisms of CXCL3 on the tumor biology of HNSCC tumor cells. The result showed that the expression level of CXCL3 in patients with HNSCC was significantly higher as compared with that in normal tissues (p<0.05). Kaplan-Meier survival analysis demonstrated that patients with high CXCL3 expression had a lower overall survival rate (p=0.038). CXCL3 was further identified as an independent prognostic factor for HNSCC patients by Cox regression analysis, and GSEA exhibited that several signaling pathways including Apoptosis, Toll-like receptor, Nod-like receptor, Jak-STAT, and MAPK signaling pathways may be involved in the tumorigenesis of HNSCC. CAL27 cells overexpressing or HNSCC cells treated with exogenous CXCL3 exhibited enhanced cell malignant behaviors, whereas downregulating CXCL3 expression resulted in decreased malignant behaviors in HSC4 cells. In addition, CXCL3 may affect the expression of several genes, including ERK1/2, Bcl-2, Bax, STAT3, and NF-κB. In summary, our bioinformatics and experiment findings effectively suggest the information of CXCL3 expression, roles, and the potential regulatory network in HNSCC.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hiroe Tada ◽  
Hideyuki Takahashi ◽  
Reika Kawabata-Iwakawa ◽  
Yurino Nagata ◽  
Miho Uchida ◽  
...  

AbstractThe emergence of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Biomarkers of the therapeutic efficacy of ICIs have been extensively investigated. In this study, we aimed to analyze whether molecular phenotypes of circulating tumor cells (CTCs) are associated with treatment responses and clinical outcomes in patients with R/M HNSCC treated with nivolumab. Peripheral blood samples were collected before treatment initiation and after four infusions of nivolumab. CTCs isolated by depletion of CD45-positive cells were analyzed to determine the expression of EPCAM, MET, KRT19, and EGFR using real-time quantitative polymerase chain reaction. CTC-positive samples were analyzed to determine the expression of PIK3CA, CCND1, SNAI1, VIM, ZEB2, CD44, NANOG, ALDH1A1, CD47, CD274, and PDCD1LG2. Of 30 patients treated with nivolumab, 28 (93.3%) were positive for CTCs. In 20 CTC-positive patients, molecular alterations in CTCs before and after nivolumab treatment were investigated. Patients with MET-positive CTCs had significantly shorter overall survival than those with MET-negative CTCs (p = 0.027). The expression level of CCND1 in CTCs of disease-controlled patients was significantly higher than that of disease-progressed patients (p = 0.034). In disease-controlled patients, the expression level of CCND1 in CTCs significantly decreased after nivolumab treatment (p = 0.043). The NANOG expression in CTCs was significantly increased in disease-controlled patients after nivolumab treatment (p = 0.036). Our findings suggest that the molecular profiling of CTCs is a promising tool to predict the treatment efficacy of nivolumab.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5590-5590
Author(s):  
Antonio Lopez-Pousa ◽  
Xavier Leon ◽  
Miquel Quer ◽  
Ana Quintana ◽  
Luis Vila ◽  
...  

5590 Background: There are not validated markers of radioresistance in patients with a head and neck squamous cell carcinoma (HNSCC). The objective of our study was to explore the relationship between response to radiotherapy and the expression at transcriptional level of a panel of genes related with the HNSCC carcinogenic process. Methods: The study group was 76 consecutive HNSCC patients treated with radiotherapy (n=51) or chemoradiotherapy (n=25) with curative intention, and a minimum follow-up of three years. Thirty-seven patients were T1-T2 tumors and 16 had an advanced tumor (T3-T4). Biopsy specimens were performed from the primary tumor before treatment and conveniently stored until processing. Expression of genes related with cell cycle (cyclin D1), apoptosis (Bcl-XL), angiogenesis (VEGF), inflammation (IL-8), and tissue invasiveness (MMP-2 and MMP-9) were examined using a RT-PCR method. The continuous value of the mRNA expression level was evaluated with a classification and regression tree (CRT) method, considering the local control of the disease achieved with radiotherapy as the dependent variable. Results: During the follow-up 26 patients (33.8%) had a local failure. The CRT method found a significant relationship between VEGF and MMP-9 expression and local control of the disease. According the expression level of VEGF and MMP-9 the patients were classified in three groups: the A group (n=19) defined by a low expression of VEGF, the B group (n=19) defined by a high expression of VEGF and a low expression of MMP-9 and the C group (n=38) defined by a high expression of both VEGF and MMP-9. The 5-year local recurrence free survival was: A group 94.7% (CI 95%: 84.7-100%), B group 83.3% (CI 95%: 66.1-100%), and C group 37.6% (CI 95%: 21.0-54.2%). There were significant differences in the local control of the disease according to the VEGF and MMP-9 expression values (test log rank, P<0.0001). Conclusions: Expression of VEGF and MMP-9 genes may be a radiosensitivity marker for patients with HNSCC treated with radical intention. We didn’t find prognostic significance for other genes explored.


2020 ◽  
Vol 19 ◽  
pp. 153303382098011
Author(s):  
Ziyan Zhou ◽  
Chang Liu ◽  
Kang Liu ◽  
Meixin Lv ◽  
Baibei Li ◽  
...  

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignancy worldwide, with high incidence and poor survival rates. Increased expression of microRNA-205-5p (miR-205-5p) may influence the outcomes of HNSCC, but the identities of miR-205-5p target genes and the potential signaling pathways related to HNSCC remain unclear. RT-qPCR was used to detect the expression levels of miR-205-5p in the plasma of patients with HNSCC. We also performed a meta-analysis using data from relevant literature, and the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases to evaluate the expression level of miR-205-5p in HNSCC. Next, we predicted the potential miR-205-5p target genes in HNSCC. We also used Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for enrichment analyses adapted to investigate the dynamics and possible mechanisms of miR-205-5p in HNSCC. Lastly, we predicted the potential miR-205-5p target genes by evaluating their expression level and using Spearman analysis. Expression of miR-205-5p was higher in HNSCC tissues compared to normal unafflicted tissue samples (P < 0.05), and the corresponding summary receiver operating characteristic (sROC) was 0.82.The pooled sensitivity, specificity, PLR, NLR, and DOR values were 0.78 (95% CI: 0.75-0.81), 0.67 (95% CI: 0.60-0.73), 2.34 (95% CI: 1.45-3.76), 0.34 (95% CI: 0.19-0.60), and 8.16 (95% CI: 4.01-16.64), respectively. Based on GO and KEGG analyses, we found that miR-205-5p was correlated with the progression of HNSCC through association with signaling pathways, including the drug metabolism-cytochrome P450 pathway. Analysis of the target genes revealed that flavin-containing monooxygenase isoform 2 (FMO2) and alcohol dehydrogenase 1B (ADH1B) may be important targets of miR-205-5p. In summary, miR-205-5p may have a significant role in the prognosis of HNSCC and may serve as a potential biomarker in HNSCC.


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