scholarly journals DIRC3 and close to NABP1 Genetics Polymorphisms correlated with Prognostic Survival in Patients with Laryngeal Squamous Cell Carcinoma

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.

2020 ◽  
Vol 66 (6) ◽  
pp. 784-788
Author(s):  
Lihua Zhang ◽  
Yu Zhang ◽  
Chunjie Zhang ◽  
Yun Hou ◽  
Fang Tian

SUMMARY OBJECTIVE Long noncoding RNA (lncRNAs) are frequently abnormally expressed in tumors and involved in the occurrence and progression of human cancer. Recently, a disease-related lncRNA, TMPO antisense RNA 1 (TMPO-AS1), was identified to be dysregulated in several tumors. Hence, we aimed to demonstrate whether TMPO-AS1 could be a promising prognostic marker for patients with laryngeal squamous cell carcinoma (LSCC). METHODS RT-PCR was performed to test TMPO-AS1 expressions in 187 LSCC specimens compared with matched normal specimens. Chi-squared tests were used to determine the associations between TMPO-AS1 expressions and the clinicopathological characteristics of LSCC patients. Then, the clinical outcome of LSCC patients who had lower or higher TMPO-AS1 expression was analyzed using Kaplan-Meier assays. Finally, a Cox proportional hazards model was carried out to evaluate the prognostic values of TMPO-AS1 and other clinical features. RESULTS We found that TMPO-AS1 was distinctly upregulated in human LSCC tissues compared with corresponding normal specimens (p < 0.01). Higher expressions of TMPO-AS1 were observed to be positively associated with the clinical stage (p = 0.020) and lymph node metastasis (p = 0.027). A clinical study in 187 patients revealed that patients with TMPO-AS1 low expressions had poorer survival than those with TMPO-AS1 high expressions (p = 0.0012). In addition, the result of multivariate assays demonstrated TMPO-AS1 expression is an independent predictor for the overall survival of LSCC patients. CONCLUSIONS TMPO-AS1 might be considered a novel molecule involved in LSCC progression, which provides a possible prognostic biomarker.


2019 ◽  
Vol 9 (1) ◽  
pp. 72 ◽  
Author(s):  
Hiroyuki Shimomura ◽  
Tomonori Sasahira ◽  
Chie Nakashima ◽  
Miyako Kurihara-Shimomura ◽  
Tadaaki Kirita

Background: Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth most common malignancy. OSCC has strong invasive ability, and its malignant potential is closely associated with local expansion and lymph node metastasis. Furthermore, local or nodal recurrence worsens OSCC prognosis. In our previous cDNA microarray analysis, non-structural maintenance of chromosome (SMC) condensin I complex subunit H (NCAPH) was identified as an upregulated gene in recurrent OSCC. Although NCAPH has several functions in tumors, its role in OSCC is unknown. Methods: In this study, we examined NCAPH expression in OSCC and performed a functional analysis of human OSCC cells. Results: NCAPH expression was higher in OSCC than in normal oral mucosa. In immunohistochemistry using 142 OSCC specimens, the immunostaining of NCAPH was strongly associated with nodal metastasis and lymphatic infiltration. In multivariate analysis using the Cox proportional hazards model, NCAPH expression was an independent poor prognostic indicator for OSCC. Moreover, NCAPH promoted the migration and adhesion of endothelial cells to OSCC cells and promoted the resistance to platinum anticancer drugs. Conclusions: Our present findings suggest that NCAPH is a novel diagnostic and therapeutic target in OSCC.


2014 ◽  
Vol 8 (2) ◽  
pp. 255-261
Author(s):  
Paramee Thongsuksai ◽  
Kowit Pruegsanusak ◽  
Pleumjit Boonyaphiphat

Abstract Background: The proteins p16, p53, Bcl-2, and Bax are important cell cycle and apoptotic regulators involved in carcinogenesis and found to have prognostic significance in various cancers. However, the data for squamous cell carcinoma of oral cavity (OSCC) and of oropharynx (OPSCC) are conflicting. Objective: We sought to determine if expression of p16, p53, Bcl-2, and Bax expression are associated with 5-year overall survival (OS) of patients with OSCC and OPSCC. Methods: One-hundred thirty-seven cases of OSCC and 140 cases of OPSCC diagnosed from January 2002 to December 2004 at Songklanagrind Hospital, Songkhla, Thailand, were analyzed using a Cox proportional hazards model for 5-year OS in relation to immunohistochemical detection of Bcl-2, Bax, p53, and p16 proteins. Results: The frequencies of p16, p53, Bcl-2, and Bax expression in OSCC were 13%, 45%, 4%, and 66%, and in OPSCC were 18%, 53%, 22%, and 75%, respectively. In univariate analysis, clinical variables including T stage, N stage and treatment were significantly associated with survival. In multivariate Cox regression, Bax overexpression was significantly associated with poor survival both in OSCC (HR 1.77, 95% CI 1.04-3.01) and in OPSCC (HR 2.21, 95% CI 1.00-4.85). We found no significant association of p16, Bcl-2, and p53 expression with survival. Conclusion: The expression pattern of p16, p53, Bcl-2, and Bax are similar in OSCC and OPSCC. Only Bax expression has prognostic significance for both tumor sites.


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.


2021 ◽  
pp. 1-10
Author(s):  
Yohei Mineharu ◽  
Yasushi Takagi ◽  
Akio Koizumi ◽  
Takaaki Morimoto ◽  
Takeshi Funaki ◽  
...  

OBJECTIVE Although many studies have analyzed risk factors for contralateral progression in unilateral moyamoya disease, they have not been fully elucidated. The aim of this study was to examine whether genetic factors as well as nongenetic factors are involved in the contralateral progression. METHODS The authors performed a multicenter cohort study in which 93 cases with unilateral moyamoya disease were retrospectively reviewed. The demographic features, RNF213 R4810K mutation, lifestyle factors such as smoking and drinking, past medical history, and angiographic findings were analyzed. A Cox proportional hazards model was used to find risk factors for contralateral progression. RESULTS Contralateral progression was observed in 24.7% of cases during a mean follow-up period of 72.2 months. Clinical characteristics were not significantly different between 63 patients with the R4810K mutation and those without it. Cox regression analysis showed that the R4810K mutation (hazard ratio [HR] 4.64, p = 0.044), childhood onset (HR 7.21, p < 0.001), male sex (HR 2.85, p = 0.023), and daily alcohol drinking (HR 4.25, p = 0.034) were independent risk factors for contralateral progression. CONCLUSIONS These results indicate that both genetic and nongenetic factors are associated with contralateral progression of unilateral moyamoya disease. The findings would serve to help us better understand the pathophysiology of moyamoya disease and to manage patients more appropriately.


2019 ◽  
Vol 15 (2) ◽  
Author(s):  
Jean de Dieu Tapsoba ◽  
Edward C. Chao ◽  
Ching-Yun Wang

Abstract Many biomedical or epidemiological studies often aim to assess the association between the time to an event of interest and some covariates under the Cox proportional hazards model. However, a problem is that the covariate data routinely involve measurement error, which may be of classical type, Berkson type or a combination of both types. The issue of Cox regression with error-prone covariates has been well-discussed in the statistical literature, which has focused mainly on classical error so far. This paper considers Cox regression analysis when some covariates are possibly contaminated with a mixture of Berkson and classical errors. We propose a simulation extrapolation-based method to address this problem when two replicates of the mismeasured covariates are available along with calibration data for some subjects in a subsample only. The proposed method places no assumption on the mixture percentage. Its finite-sample performance is assessed through a simulation study. It is applied to the analysis of data from an AIDS clinical trial study.


Hand ◽  
2016 ◽  
Vol 12 (5) ◽  
pp. 446-452 ◽  
Author(s):  
Suzanne C. Wilkens ◽  
Zichao Xue ◽  
Jos J. Mellema ◽  
David Ring ◽  
Neal Chen

Background: Trapeziometacarpal (TMC) arthritis is an expected part of ageing to which most patients adapt well. Patients who do not adapt to TMC arthritis may be offered operative treatment. The factors associated with reoperation after TMC arthroplasty are incompletely understood. The purpose of this study was to determine the rate of, the underlying reasons for, and the factors associated with unplanned reoperation after TMC arthroplasty. Methods: In this retrospective study, we included all adult patients who had TMC arthroplasty for TMC arthritis at 1 of 3 large urban area hospitals between January 2000 and December 2009. Variables were inserted into a multivariable Cox proportional hazards model to determine factors associated with unplanned reoperation, and the Kaplan-Meier curve was used to estimate and describe the probability of unplanned reoperation over time. Results: Among 458 TMC arthroplasties, 19 (4%) had an unplanned reoperation; 16 of 19 (84%) for persistent pain and two-thirds within the first year. The multivariate Cox regression analysis showed that unplanned reoperation was independently associated with younger age, surgeon inexperience, and index procedure type. Conclusions: Surgeons should be aware as well as patients should be informed that as many as 4% are offered or request a second surgery, usually for persistent pain and often within the 1-year window when additional improvement is anticipated.


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.


Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3248
Author(s):  
Eric Miller ◽  
Ansel Nalin ◽  
Dayssy Diaz Pardo ◽  
Andrea Arnett ◽  
Laith Abushahin ◽  
...  

The optimal treatment for stage I squamous cell carcinoma of the anus (SCCA) remains undefined. Recently, wide local excision alone was found to have comparable survival to those treated with chemoradiation (CRT). Given that local excision may be sufficient for the treatment of stage I SCCA, we hypothesized that radiation therapy (RT) alone, compared to CRT would result in equivalent overall survival (OS) in this population. We identified non-surgically treated patients with stage I SCCA from the National Cancer Database from 2004–2015. We included only patients treated either with CRT (45–59.4 Gy with chemotherapy initiated within 14 days of RT) or RT alone (45–59.4 Gy with no chemotherapy). The primary endpoint was OS between CRT and RT patients. Propensity-score matched (PSM) analysis was performed to determine the effect of concurrent chemotherapy on OS using a Cox proportional hazards model with robust standard error to account for clustering in matched pairs. We identified 3552 stage I patients treated with CRT and 287 treated with RT. Compared to patients treated with CRT, those that received RT were more likely to be ≥70 years old (33.1% vs. 19.7%, p < 0.001) and less likely to be female (63.1% vs. 71.0%, p < 0.001). The proportion of patients with a Charlson-Deyo score of 0 was similar in both groups (80.8% RT vs. 82.7% CRT, p = 0.164). The PSM cohort consisted of 287 pairs of patients with median follow-up 48.3 months (interquartile range, 24.4–85.1 months) and 151 deaths (86 RT, 65 CRT). CRT was associated with a 31% reduction in the risk of death (HR = 0.69, 95% CI 0.50–0.95, p = 0.023). We found that CRT was associated with improved OS, compared to RT alone, in patients with non-surgically treated stage I SCCA. These data suggest that de-intensification of therapy in stage I SCCA must be used with caution. However, given the retrospective nature of the data, prospective trials are required.


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