scholarly journals Clinical Significance of miR-149 in the Survival of Patients with Laryngeal Squamous Cell Carcinoma

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Yi Xu ◽  
Yun-Peng Lin ◽  
Dong Yang ◽  
Geng Zhang ◽  
Hui-Fang Zhou

MicroRNAs (miRNAs) play critical roles in the progression of laryngeal cancer (LC). In this study, we aimed to investigate whether miR-149 is associated with the prognosis of patients with LC. A total of 97 laryngeal squamous cell carcinoma patients who underwent tumor resection were included in our follow-up study.In vitrostudies was performed in cancer cell line Hep-2 to explore the antitumor role of miR-149 in LC. We found that the expression of miR-149 was significantly lower in tumor tissues, compared with vocal cord polyp tissues (P<0.05). Kaplan-Meier analysis revealed that miR-149 expression status is significantly associated with survival duration (log rank test,P<0.05), and multivariate Cox regression analysis revealed that patients with low miR-149 expression had shorter survival times compared with patients with high miR-149 expression.In vitrostudies revealed that the exogenous expression of miRNA-149 inhibits the proliferation of human Hep-2 cells and induces cell apoptosis. Our study suggests that miR-149 expression in laryngeal squamous cell carcinoma tissues is critically associated with the prognosis of patients, and the ectopic expression of miR-149 in Hep-2 cells inhibits proliferation and cell cycle progression.

2020 ◽  
Author(s):  
Qun Zhang ◽  
Feng Li ◽  
Peng Cai ◽  
Hongwei Li ◽  
Hongmei Yin ◽  
...  

Abstract Background To investigate the expression of PD-L1(programmed death-ligand 1)in patients with esophageal squamous cell carcinoma (ESCC) and its clinical significance. Methods The tissue expression of PD-L1 protein in 139 cases of ESCC and 50 adjacent non-malignant epithelial tissues (> 5 cm from the tumor resection margins) were identified by immunohistochemical staining. Subsequently, the relationship between expression and the observed clinical characteristics was analyzed. Results The positive expression rate of PD-L1 protein was increased in tumor tissues compared to that of adjacent noncancerous mucosa tissues (40.3% vs. 22.0%, P < 0.05). The findings also indicated that PD-L1 protein expression had no significant correlation with age, gender, tumor location, differentiation and lymph node (N) status (P > 0.05). The 91 months follow-up Kaplan-Meier survival analysis showed that patients in positively expressed PD-L1 group experienced a lower survival rate compared to their negatively expressed PD-L1 counterparts (32.1% vs. 48.2%, P < 0.05). The COX regression analysis results suggested that PD-L1 represented an independent prognosis factor for ESCC. Conclusions The findings indicated that PD-L1 plays an important role in the progression of ESCC and might represent a potential therapeutic and prognostic target for ESCC patients.


2020 ◽  
Author(s):  
Yujie Shen ◽  
Han Zhou ◽  
Shikun Dong ◽  
Meiping Lu ◽  
Weida Dong ◽  
...  

Abstract Background: The immune system greatly affects the prognosis of various malignancies. Studies on differentially expressed immune-related genes (IRGs) in the immune microenvironment of laryngeal squamous cell carcinoma (LSCC) have rarely been reported.Methods: In this paper, the prognostic potentials of IRGs in LSCC were explored. The RNAseq dataset containing differentially expressed IRGs and corresponding clinical information of LSCC patients was obtained from The Cancer Genome Atlas (TCGA). A total of 371 up-regulated and 61 down-regulated IRGs were identified. Subsequent functional enrichment analysis revealed that the pathway of IRGs was mainly enriched in the cytokine-cytokine receptor interaction. Then, 30 IRGs with prognostic potentials in LSCC were screened out, and the regulatory network induced by relevant transcription factors (TFs) were constructed.Results: Finally, multivariate Cox regression analysis was conducted to assess the prognostic potential of 15 IRGs after adjustment of clinical factors and LSCC patients were classified into 2 subgroups based on different outcomes. The gene expression of the model was verified by other independent databases. Nomogram including the 15 IRGs signature was established and shown some clinical net beneft. Intriguingly, B cells were significantly enriched in the low-risk group. Conclusion:These findings may contribute to the development of potential therapeutic targets and biomarkers for the new-immunotherapy of LSCC.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7456 ◽  
Author(s):  
Lian Hui ◽  
Jing Wang ◽  
Jialiang Zhang ◽  
Jin Long

Background Long non-coding RNAs (lncRNAs) can function as competing endogenous RNAs (ceRNAs) to interact with miRNAs to regulate target genes and promote cancer initiation and progression. The expression of lncRNAs and miRNAs can be epigenetically regulated. The goal of this study was to construct an lncRNA-miRNA-mRNA ceRNA network in laryngeal squamous cell carcinoma (LSCC) and reveal their methylation patterns, which was not investigated previously. Methods Microarray datasets available from the Gene Expression Omnibus database were used to identify differentially expressed lncRNAs (DELs), miRNAs (DEMs), and genes (DEGs) between LSCC and controls, which were then overlapped with differentially methylated regions (DMRs). The ceRNA network was established by screening the interaction relationships between miRNAs and lncRNAs/mRNAs by corresponding databases. TCGA database was used to identify prognostic biomarkers. Results Five DELs (downregulated: TMEM51-AS1, SND1-IT1; upregulated: HCP5, RUSC1-AS1, LINC00324) and no DEMs were overlapped with the DMRs, but only a negative relationship occurred in the expression and methylation level of TMEM51-AS1. Five DELs could interact with 11 DEMs to regulate 242 DEGs, which was used to construct the ceRNA network, including TMEM51-AS1-miR-106b-SNX21/ TRAPPC10, LINC00324/RUSC1-AS1-miR-16-SPRY4/MICAL2/ SLC39A14, RUSC1-AS1-miR-10-SCG5 and RUSC1-AS1-miR-7-ZFP1 ceRNAs axes. Univariate Cox regression analysis showed RUSC1-AS1 and SNX21 were associated with overall survival (OS); LINC00324, miR-7 and ZFP1 correlated with recurrence-free survival (RFS); miR-16, miR-10, SCG5, SPRY4, MICAL2 and SLC39A14 were both OS and RFS-related. Furthermore, TRAPPC10 and SLC39A14 were identified as independent OS prognostic factors by multivariate Cox regression analysis. Conclusion DNA methylation-mediated TMEM51-AS1 and non-methylation-mediated RUSC1-AS1 may function as ceRNAs for induction of LSCC. They and their ceRNA axis genes (particularly TMEM51-AS1-miR-106b-TRAPPC10; RUSC1-AS1-miR-16-SLC39A14) may be potentially important prognostic biomarkers for LSCC.


2016 ◽  
Author(s):  
Zhen Shen ◽  
Wanli Ren ◽  
Yanxia Bai ◽  
Zhengshuai Chen ◽  
Jingjie Li ◽  
...  

Laryngeal squamous cell carcinoma (LSCC) is one of the most common and aggressive malignancies in the upper digestive tract that has a high mortality rate and a poor prognosis. Prognostic factors were determined through multivariate Cox regression analysis. The overall survival rates were calculated by the Kaplan-Meier method. The SPSS statistical software package version 17.0 (SPSS Inc., Chicago, IL, USA) was used for all analyses. Median follow-up was 38 (range 3-122) months and the median survival time was 48 months. We adjusted to confounding factors (total laryngectomy, poor differentiation, T3-T4 stage, N1-N2 stage, III-IV TNM stage) into multivariate Cox proportional hazards model, we confirmed rs11903757 GT genotype (HR = 2.036; 95% CI, 1.071 - 3.872; p = 0.030) and rs966423 TT genotype (HR = 11.677; 95% CI, 3.901 - 34.950; p = 0.000) were significantly correlated with prognostic survival of patients with LSCC compared with rs11903757 TT genotype and rs966423 CC genotype, respectively. Our research provided new evidence for patients with LSCC, it seemed to be the first that demonstrated rs11903757 GT genotype on chromosome 2q32.3 close to NABP1 and rs966423 TT genotype in the intron region of DIRC3 on chromosome 2q35 predict poor prognostic survival in patients with LSCC.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guichuan Huang ◽  
Jing Zhang ◽  
Ling Gong ◽  
Yi Huang ◽  
Daishun Liu

Abstract Background Lung cancer is one of the most lethal and most prevalent malignant tumors worldwide, and lung squamous cell carcinoma (LUSC) is one of the major histological subtypes. Although numerous biomarkers have been found to be associated with prognosis in LUSC, the prediction effect of a single gene biomarker is insufficient, especially for glycolysis-related genes. Therefore, we aimed to develop a novel glycolysis-related gene signature to predict survival in patients with LUSC. Methods The mRNA expression files and LUSC clinical information were obtained from The Cancer Genome Atlas (TCGA) dataset. Results Based on Gene Set Enrichment Analysis (GSEA), we found 5 glycolysis-related gene sets that were significantly enriched in LUSC tissues. Univariate and multivariate Cox proportional regression models were performed to choose prognostic-related gene signatures. Based on a Cox proportional regression model, a risk score for a three-gene signature (HKDC1, ALDH7A1, and MDH1) was established to divide patients into high-risk and low-risk subgroups. Multivariate Cox regression analysis indicated that the risk score for this three-gene signature can be used as an independent prognostic indicator in LUSC. Additionally, based on the cBioPortal database, the rate of genomic alterations in the HKDC1, ALDH7A1, and MDH1 genes were 1.9, 1.1, and 5% in LUSC patients, respectively. Conclusion A glycolysis-based three-gene signature could serve as a novel biomarker in predicting the prognosis of patients with LUSC and it also provides additional gene targets that can be used to cure LUSC patients.


2021 ◽  
Vol 8 (1) ◽  
pp. e000492
Author(s):  
Sarah Derby ◽  
Matthew Forshaw ◽  
Caroline Lowrie ◽  
Derek Grose ◽  
Husam Marashi ◽  
...  

BackgroundOesophageal cancer remains a common cause of cancer mortality worldwide. Increasingly, oncology centres are treating an older population and comorbidities may preclude multimodality treatment with chemoradiotherapy (CRT). We review outcomes of radical radiotherapy (RT) in an older population treating squamous cell carcinoma (SCC) oesophagus.MethodsPatients over 65 years receiving RT for SCC oesophagus between 2013 and 2016 in the West of Scotland were identified. Kaplan-Meier and Cox-regression analysis were used to compare overall survival (OS) between patients treated with radical RT and radical CRT.ResultsThere were 83 patients over 65 years treated with either RT (n=21) or CRT (n=62). There was no significant difference in median OS between CRT versus RT (26.8 months vs 28.5 months, p=0.92). All patients receiving RT completed their treatment whereas 11% of CRT patients did not complete treatment.ConclusionSurvival in this non-trial older patient group managed with CRT is comparable to that reported in previous trials. RT shows better than expected outcomes which may reflect developments in RT technique. This review supports RT as an alternative in older patients, unfit for concurrent treatment.


Author(s):  
Nattinee Charoen ◽  
Kitti Jantharapattana ◽  
Paramee Thongsuksai

Objective: Programmed cell death ligand 1 (PD-L1) and mammalian target of rapamycin (mTOR) are key players in host immune evasion and oncogenic activation, respectively. Evidence of the prognostic role in oral squamous cell carcinoma (OSCC) is conflicting. This study examined the associations of PD-L1 and mTOR expression with 5-year overall survival in OSCC patients. Material and Methods: The expressions of PD-L1 and mTOR proteins were immunohistochemically evaluated on tissue microarrays of 191 patients with OSCC who were treated by surgery at Songklanagarind Hospital, Thailand from 2008 to 2011. Cox regression analysis was used to determine independent prognostic factors. Results: PD-L1 expression was observed in 14.1% of cases while mTOR expression was present in 74.3% of cases. Females were more likely to have tumors with PD-L1 (p-value=0.007) and mTOR expressions (p-value=0.003) than males. In addition, lower clinical stage and well differentiated tumor are more likely to have mTOR expression (p-value= 0.038 and p-value<0.001, respectively). Cox regression analysis showed that age, tumor stage, nodal stage, combined surgical treatment with radiation or chemoradiation therapy, surgical margin status, PD-L1 expression and mTOR expression are independent prognostic factors. High PD-L1 expression (hazard ratio (HR) 3.14, 95% confidence interval (CI), 1.26–7.79) and high mTOR expression (HR 1.69, 95% CI, 1.00–2.84) are strong predictors of poor outcome. Conclusion: A proportion of OSCC expressed PD-L1 and mTOR proteins. Expression of PD-L1 and mTOR proteins are strong prognostic factors of OSCC.


2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Wei Gao ◽  
Yuliang Zhang ◽  
Hongjie Luo ◽  
Min Niu ◽  
Xiwang Zheng ◽  
...  

Abstract Spindle and kinetochore-associated complex subunit 3 (SKA3) is a well-known regulator of chromosome separation and cell division, which plays an important role in cell proliferation. However, the mechanism of SKA3 regulating tumor proliferation via reprogramming metabolism is unknown. Here, SKA3 is identified as an oncogene in laryngeal squamous cell carcinoma (LSCC), and high levels of SKA3 are closely associated with malignant progression and poor prognosis. In vitro and in vivo experiments demonstrate that SKA3 promotes LSCC cell proliferation and chemoresistance through a novel role of reprogramming glycolytic metabolism. Further studies reveal the downstream mechanisms of SKA3, which can bind and stabilize polo-like kinase 1 (PLK1) protein via suppressing ubiquitin-mediated degradation. The accumulation of PLK1 activates AKT and thus upregulates glycolytic enzymes HK2, PFKFB3, and PDK1, resulting in enhancement of glycolysis. Furthermore, our data reveal that phosphorylation at Thr360 of SKA3 is critical for its binding to PLK1 and the increase in glycolysis. Collectively, the novel oncogenic signal axis “SKA3-PLK1-AKT” plays a critical role in the glycolysis of LSCC. SKA3 may serve as a prognostic biomarker and therapeutic target, providing a potential strategy for proliferation inhibition and chemosensitization in tumors, especially for LSCC patients with PLK1 inhibitor resistance.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ying Zheng ◽  
Bowen Zheng ◽  
Xue Meng ◽  
Yuwen Yan ◽  
Jia He ◽  
...  

Abstract Background Tongue squamous cell carcinoma (TSCC) is a most invasive cancer with high mortality and poor prognosis. It is reported that lncRNA DANCR has implications in multiple types of cancers. However, its biological role and underlying mechanism in TSCC progress are not well elucidated. Methods Our present study first investigated the function of DANCR on the proliferation, migration and invasion of TSCC cells by silencing or overexpressing DANCR. Further, the miR-135a-5p-Kruppel-like Factor 8 (KLF8) axis was focused on to explore the regulatory mechanism of DANCR on TSCC cell malignant phenotypes. Xenografted tumor growth using nude mice was performed to examine the role of DANCR in vivo. Results DANCR knockdown reduced the viability and inhibited the migration and invasion of TSCC cells in vitro, while ectopic expression of DANCR induced opposite effects. In vivo, the tumor growth and the expression of matrix metalloproteinase (MMP)-2/9 and KLF8 were also blocked by DANCR inhibition. In addition, we found that miR-135-5p directly targeted DANCR, which was negatively correlated with DANCR on TSCC progression. Its inhibition reversed the beneficial effects of DANCR silence on TSCC malignancies. Furthermore, the expression of KLF8 evidently altered by both DANCR and miR-135a-5p. Silencing KLF8 using its specific siRNA showed that KLF8 was responsible for the induction of miR-135a-5p inhibitor on TSCC cell malignancies and MMP-2/9 expression. Conclusions These findings, for the first time, suggest that DANCR plays an oncogenic role in TSCC progression via targeting miR-135a-5p/KLF8 axis, which provides a promising biomarker and treatment approach for preventing TSCC.


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