scholarly journals lncRNA TMEM51-AS1 and RUSC1-AS1 function as ceRNAs for induction of laryngeal squamous cell carcinoma and prediction of prognosis

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.

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.


2021 ◽  
Author(s):  
Xiang Lv ◽  
Songtao Han ◽  
Bin Xu ◽  
Yuqin Deng ◽  
Feng Yangchun

Abstract Objective To investigate the value of complete blood count in predicting the survival rate of patients with esophageal squamous cell carcinoma. Methods A total of 3587 patients with esophageal squamous cell carcinoma who were initially admitted to the Affiliated Cancer Hospital of Xinjiang Medical University from January 2010 to December 2017 were collected by retrospective study. The relevant clinical data were collected by the medical record system, and the patients were followed up by the hospital medical record follow-up system. The follow-up outcome was death. The survival time of all patients was obtained. The survival curve was established using the cut-off value of each index obtained by ROC curve. The Cox proportional hazards regression analysis model and nomogram were established to predict the survival prognosis of esophageal squamous cell carcinoma. The role of each index in the prognosis of patients with esophageal squamous cell carcinoma was studied Results The cut-off values of NLR, NMR, LMR, RDW and PDW in blood routine were 3.52, 10.22, 2.25, 13.85% and 12.05%, respectively. Survival curve analysis showed that patients aged < 60 years and NLR < 3.52 had survival. All indicators were divided into high and low groups according to ROC curve. Univariate Cox regression analysis model showed that RDW (≥ 13.85) and NLR (≥ 3.52) groups were risk factors for the prognosis of ESCC, with HR values of 1.099 (1.015–1.191; p = 0.020) and 1.340 (1.231–1.458; p < 0.001) compared with RDW (< 13.85) and NLR (< 3.52), respectively; multivariate Cox regression analysis model showed that NLR was significantly associated with the prognosis of ESCC, with HR of 1.342 (1.232–1.461; p < 0.001) for NLR (≥ 3.52) NLR (< 3.52). Conclusion NLR results in blood count can be used to predict the survival of patients with esophageal squamous cell carcinoma.


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.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chenguang Zhao ◽  
Yingrui Zhou ◽  
Hongwei Ma ◽  
Jinhui Wang ◽  
Haoliang Guo ◽  
...  

Abstract Background Oral squamous cell carcinoma (OSCC) is one of the most common maligancies of the head and neck. The prognosis was is significantly different among OSCC patients. This study aims to identify new biomarkers to establish a prognostic model to predict the survival of OSCC patients. Methods The mRNA expression and corresponding clinical information of OSCC patients were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus. Additionally, a total of 26 hypoxia-related genes were also obtained from a previous study. Univariate Cox regression analysis and LASSO Cox regression analysis were performed to screen the optimal hypoxia-related genes which were associated with the prognosis of OSCC. to establish the predictive model (Risk Score) was established for estimating the patient's overall survival (OS). Multivariate Cox regression analysis was used to determine whether the Risk Score was an independent prognostic factor. Based on all the independent prognostic factors, nomogram was established to predict the OS probability of OSCC patients. The relative proportion of 22 immune cell types in each patient was evaluated by CIBERSORT software. Results We determined that a total of four hypoxia-related genes including ALDOA, P4HA1, PGK1 and VEGFA were significantly associated with the prognosis of OSCC patients. The nomogram established based on all the independent factors could reliably predict the long-term OS of OSCC patients. In addition, our resluts indicated that the inferior prognosis of OSCC patients with high Risk Score might be related to the immunosuppressive microenvironments. Conclusion This study shows that high expression of hypoxia-related genes including ALDOA, P4HA1, PGK1 and VEGFA is associated with poor prognosis in OSCC patients, and they can be used as potential markers for predicting prognosis in OSCC patients.


2020 ◽  
Vol 29 ◽  
pp. 096368972092930
Author(s):  
Zeng-hong Wu ◽  
Yun-Tang ◽  
Qing Cheng

Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor of the upper aerodigestive tract affecting the oral cavity, lips, paranasal sinuses, larynx, and nasopharynx. Proteogenomics combines proteomics and genomics and employs mass spectrometry and high-throughput sequencing technologies to identify novel peptides. The aim of this study was to identify potential protein biomarkers for clinical treatment of HNSCC. To achieve this, we utilized two sets of data, one on proteins from The Cancer Proteome Atlas (TCPA) and the other on gene expression from The Cancer Genome Atlas (TCGA) database, to evaluate dysfunctional proteogenomics microenvironment. Univariate Cox regression analysis was performed to examine the relationship between protein signatures and prognosis. A total of 19 proteins were significantly associated with overall survival (OS) of patients, of which E2F transcription factor 1 (E2F1; HR = 4.557, 95% CI = 1.810 to 11.469) and enhancer of zeste homolog 2 (EZH2; HR = 0.430, 95% CI = 0.187 to 0.984) were the most differentially expressed between patients with longer and shorter OS, respectively. Furthermore, multivariate Cox regression analysis on six proteins (ERALPHA, HER3, BRAF, P27, RAPTOR, and E2F1) was performed to build the prognostic model. The receiver operating characteristic curves were used to determine whether the expression pattern of survival-related proteins could provide an early prediction of the occurrence of HNSCC. Herein, we found an AUC of 0.720. Based on an online database, we identified novel protein markers for the prognosis of HNSCC. The findings of the present study may provide new insights into the development of new and reliable tools for precise cancer intervention.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Haishan Wu ◽  
Yilin Yu ◽  
Qunhao Zheng ◽  
Tianxiu Liu ◽  
Yahua Wu ◽  
...  

Abstract Objective There is still no definitely therapeutic evidence of a beneficial effect of chemotherapy with radiotherapy for older patients with esophageal squamous cell carcinoma (ESCC). We aim to determine the influence of chemoradiotherapy (CRT) and radiotherapy (RT) alone in patients aged 65 years or older with locally advanced ESCC. Methods We retrospectively analyzed 581 ESCC patients who underwent CRT and RT alone. Univariate and multivariate Cox regression analysis was used to analyze the impact of clinical factors on long‐term overall survival (OS) and progression-free survival (PFS). Finally, we compared the toxicity rates of these patients. Results The median OS and PFS of the overall population were 23.2 months (2.0–162.6 months) and 18.6 months (1.1–159.6 months). Multivariate Cox regression analysis showed that chemotherapy (p < 0.05), tumor thickness (p < 0.01), and N stage (p < 0.05) were independent prognostic factors associated with both OS and PFS. In the chemotherapy subgroup, patients who received 2–8 cycles of chemotherapy had better OS than those who received 1 cycle (p = 0.015). The results also revealed that the CRT group has better OS and PFS than RT alone group for patients aged 65–74 years (both p < 0.01). However, for patients aged 75 years or older, there was no statistically significant difference between CRT and RT alone (both p > 0.05). Besides, higher staged ESCC has the inferior OS and PFS than lower staged ESCC for patients received RT alone and aged 65–74 years (both p < 0.05). Finally, there were significantly more severe hematologic toxicities in the CRT group than in those treated with RT alone in this study (p < 0.001). Conclusions The present study suggested that CRT for locally advanced ESCC in patients aged 65 years or older had a significant benefit over RT alone in terms of OS and PFS. However, for patients aged 75 years or older, there was no statistically significant difference between CRT and RT alone. CRT should be performed with special attention in patients aged 75 years or older.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
LangXiong Chen ◽  
XiaoSong He ◽  
ShiJiang Yi ◽  
GuanCheng Liu ◽  
Yi Liu ◽  
...  

Objective. Head and neck squamous cell carcinoma (HNSCC) is one of the worst-prognosis malignant tumors. This study used bioinformatic analysis of the transcriptome sequencing data of HNSCC and the patients’ survival and clinical data to construct a prediction signature of glycolysis-related genes as the prognostic risk markers. Methods. Gene expression profile data about HNSCC tissues ( n = 498 ) and normal tissues in the head and neck ( n = 44 ) were got from The Cancer Genome Atlas (TCGA), as well as patients’ survival and clinical data. Then, we obtained core genes; their expression in head and neck squamous cell carcinoma tissues is significantly different from that in normal head and neck tissues. The predicted glycolysis-related genes are screened through univariate Cox regression analysis, and then, the prognostic risk markers were constructed through further correction of multivariate Cox regression analysis. The Kaplan-Meier curve and receiver operating characteristic curve are used to analyze the potential value of these risk markers in diagnosis and prognosis. We also evaluated that the glycolysis-related prognostic risk markers composed of 6 oncogenes are correlated with clinical features, such as age, gender, grade, and clinical stage of the tumor, by univariate and multivariate Cox regression analyses. Results. Differentially expressed glycolytic genes in HNSCC tissues and normal head and neck tissues were screened from TCGA databases using the bioinformatic method. We confirmed a set of six glycolytic genes that were significantly associated with OS in the test series. According to our analysis, the prognostic risk markers composed of HPRT1, STC2, PLCB3, GPR87, PYGL, and SLC5A12 may be an independent risk factor for the prognosis of HNSCC. Conclusions. Through this analysis, we constructed new prognostic risk markers related to glycolysis as a prognostic risk marker for patients with HNSCC and provided new ideas and molecular targets for the research and individualized treatment of HNSCC.


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.


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.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuzi Xu ◽  
Fengqin Xu ◽  
Yiming Lv ◽  
Siyuan Wang ◽  
Jia Li ◽  
...  

AbstractHead and neck squamous cell carcinoma (HNSCC) is one of the most malignant cancers with poor prognosis worldwide. Emerging evidence indicates that competing endogenous RNAs (ceRNAs) are involved in various diseases, however, the regulatory mechanisms of ceRNAs underlying HNSCC remain unclear. In this study, we retrieved differentially expressed long non-coding RNAs (DElncRNAs), messenger RNAs (DEmRNAs) and microRANs (DEmiRNAs) from The Cancer Genome Atlas database and constructed a ceRNA-based risk model in HNSCC by integrated bioinformatics approaches. Functional enrichment analyses showed that DEmRNAs might be involved in extracellular matrix related biological processes, and protein–protein interaction network further selected out prognostic genes, including MYL1 and ACTN2. Importantly, co-expressed RNAs identified by weighted co-expression gene network analysis constructed the ceRNA networks. Moreover, AC114730.3, AC136375.3, LAT and RYR3 were highly correlated to overall survival of HNSCC by Kaplan–Meier method and univariate Cox regression analysis, which were subsequently implemented multivariate Cox regression analysis to build the risk model. Our study provides a deeper understanding of ceRNAs on the regulatory mechanisms, which will facilitate the expansion of the roles on the ceRNAs in the tumorigenesis, development and treatment of HNSCC.


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