scholarly journals Role of the TGFβ/PDCD4/AP-1 Signaling Pathway in Nasopharyngeal Carcinoma and Its Relationship to Prognosis

2017 ◽  
Vol 43 (4) ◽  
pp. 1392-1401 ◽  
Author(s):  
Jie Ma ◽  
Shu-Hong Xuan ◽  
Yan Li ◽  
Zhi-Ping Zhang ◽  
Xin-Hua Li
Keyword(s):  
Regression Analysis ◽  
Prognostic Factors ◽  
Nasopharyngeal Carcinoma ◽  
Cox Regression ◽  
Advanced Tumor Stage ◽  
Cox Regression Analysis ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Low Expression

Background: The objective of the present study was to evaluate the role of the TGFβ/PDCD4/AP-1 pathway in nasopharyngeal carcinoma (NPC) and its relationship to NPC prognosis. Methods: NPC tissues collected from 66 NPC patients were compared to 17 nasopharyngeal mucosa biopsy specimens collected as normal tissues. Immunohistochemical staining was performed to assess expression of transforming growth factor-β receptor I (TGFβRI), programmed cell death 4 (PDCD4) and activator protein-1 (AP-1). The Kaplan-Meier method was applied to evaluate NPC patient overall survival (OS) and progression-free-survival (PFS). Cox regression analysis was used to estimate independent prognostic factors for NPC. The human NPC cell line CNE2 was selected and treated with SB431542, an inhibitor of TGFβRI; expression of TGFβRI and PDCD4 in CNE2 cells was determined by western blotting. NPC tissues showed higher expression of TGFβRI and AP-1 but lower expression of PDCD4 than normal tissues (all P < 0.05). Results: The results of Kaplan-Meier analysis showed that TGFβRI-positive patients and AP-1-positive patients had shorter OS and PFS than TGFβRI-negative patients and AP-1-negative patients; additionally, PDCD4-positive patients had higher OS and PFS than PDCD4-negative patients. Cox regression analysis revealed that advanced tumor stage, overexpression of TGFβRI and AP-1, and low expression of PDCD4 were unfavorable factors influencing OS and PFS in NPC patients. Compared with the control group, expression of TGFβRI decreased and that of PDCD4 increased significantly in CNE2 cells treated with the inhibitor (all P < 0.05). These findings indicate that the TGFβ/PDCD4/AP-1 pathway may be associated with NPC development and progression. Conclusion: High expression of TGFβRI and AP-1 and low expression of PDCD4 may be unfavorable prognostic factors for NPC.

scholarly journals Expression Status and Prognostic Value of m6A RNA Methylation Regulators in Lung Adenocarcinoma

2020 ◽  
Author(s):  
Rui Wang ◽  
Zian Feng ◽  
Jie Hu ◽  
Xiaodong He ◽  
Zuojun Shen
Keyword(s):  
Regression Analysis ◽  
Survival Analysis ◽  
Roc Curve ◽  
Cox Regression ◽  
Risk Group ◽  
Cox Regression Analysis ◽  
Rna Methylation ◽  
Kaplan Meier ◽  
Prediction Efficiency

Abstract Background: N6-methyladenosine (m6A) RNA modification is the most abundant modification method in mRNA, and it plays an important role in the occurrence and development of many cancers. However, data on the role of m6A RNA methylation regulators in lung adenocarcinoma (LUAD) are still lacking. This paper mainly discusses the role of m6A RNA methylation regulators in LUAD, to identify novel prognostic biomarkers.Methods: The gene expression data of 19 m6A methylation regulator in LUAD patients and its relevant clinical parameters were extracted from The Cancer Genome Atlas (TCGA) database. The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm were performed to construct a risk signature and evaluated its prognostic prediction efficiency by using the receiver operating characteristic (ROC) curve. The risk score of each patient was calculated according to the risk signature, and LUAD patients were divided into high-risk group and low-risk group. Kaplan-Meier survival analysis and Cox regression analysis were used to identify the independent prognostic significance of risk signature. Finally, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the differential signaling pathways and cellular processes between the two groups.Results: The expression of 15 m6A RNA methylation regulators in LUAD tissues was significantly different than that in normal tissues. YTHDF3, YTHDF2, KIAA1429, HNRNPA2B1, RBM15, METTL3, HNRNPC, YTHDF1, IGF2BP2, IGF2BP3, IGF2BP1 were significantly up-regulated in LUAD, and the expressions of FTO, ZC3H13, WTAP, and METL14 were significantly down-regulated. We selected IGF2BP1, HNRNPC, and HNRNPA2B1 to construct the risk signature. ROC curve indicated the area under the curve (AUC) was 0.659, which means the risk signature had a good prediction efficiency. The results of Kaplan-Meier survival analysis and Cox regression analysis showed that the risk score can be used as an independent prognostic factor for LUAD.Conclusions: The m6A RNA methylation regulators IGF2BP1, HNRNPC, and HNRNPA2B1 have a significant correlation with the clinicopathological characteristics of LUAD, which may be a promising prognostic feature and clinical treatment target.

Associations between TAB2 gene polymorphisms and dilated cardiomyopathy in a Chinese population

2020 ◽  
Author(s):  
Can Shen ◽  
Yue Zhong ◽  
Xingming Huang ◽  
Yanyun Wang ◽  
Ying Peng ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Survival Analysis ◽  
Dilated Cardiomyopathy ◽  
Gene Polymorphisms ◽  
Chinese Population ◽  
Cox Regression ◽  
Bonferroni Correction ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Aim: The present study aimed to investigate the role of TAB2 gene polymorphisms in dilated cardiomyopathy (DCM) susceptibility and prognosis in a Chinese population. Materials & methods: A total of 343 DCM patients and 451 controls were enrolled and had their blood genotyped. Survival analysis was evaluated with Kaplan-Meier curves and Cox regression analysis. Results: G carriers (AG/GG) and AG genotype of rs237028 had a higher DCM susceptibility as well as a worse DCM prognosis. Additionally, C carriers (CT/CC) of rs652921 and G carriers (TG/GG) of rs521845 had a higher DCM risk and CC homozygote of rs652921 had a worse DCM prognosis. These associations were still significant after adjustment for the Bonferroni correction. Conclusion: TAB2 gene polymorphisms were associated with DCM susceptibility and prognosis in the Chinese population.

scholarly journals The relationship between miR-219-5p Gene Polymorphisms and the prognosis of colorectal cancer

2020 ◽  
Author(s):  
Yang Yan ◽  
Xiaohui Du ◽  
Shaoyou Xia ◽  
Songyan Li ◽  
Da Teng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Regression Analysis ◽  
Prognostic Value ◽  
Cox Regression ◽  
Malignant Tumors ◽  
Survival Rates ◽  
Tnm Staging ◽  
Cox Regression Analysis ◽  
Normal Tissues ◽  
Kaplan Meier

Abstract Background Colorectal cancer (CRC) is one of the most common malignant tumors, its morbidity and mortality are increasing year by year, it is a serious threat to people's health. Some studies have reported that miR-219-5p acts as a tumor suppressor in some malignant tumors. So the purpose of this study was to investigate the prognostic value of miR-219-5p expression in CRC patients. Methods QRT-PCR was used to detect the expression levels of miR-219-5p in CRC tissues and corresponding normal tissues (P < 0.001). The prognostic value of miR-219-5p in CRC was analyzed by Kaplan-Meier and Cox regression analysis. Results The results indicated that the expression of miR-219-5p was significantly lower in CRC tissues, and its expression was closely correlated with tumor differentiation, TNM staging and lymph node metastasis (all P < 0.05). Moreover, Kaplan Meier survival analysis showed that the patients with low expression of miR-219-5p had worse overall survival rates (P < 0.05). Cox regression analysis further demonstrated that miR-219-5p expression was an independent prognostic factor for survival time in CRC patients (P = 0.018, HR = 2.026 and 95%CI: 1.127–3.643). Conclusions All the results suggest that miR-219-5p expression can be used as a potential prognostic biomarker for CRC patients.

scholarly journals Low Expression of RILPL2 Predicts Poor Prognosis and Correlates with Immune Infiltration in Endometrial Carcinoma

2021 ◽  
Author(s):  
Jinihui Liu ◽  
Xu Mengtimg ◽  
Zhipemg Wu ◽  
Jianqiamg Liamg ◽  
Hongjun Zhu
Keyword(s):  
Regression Analysis ◽  
Endometrial Carcinoma ◽  
Immune Cell ◽  
Cox Regression ◽  
Critical Role ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Low Expression

Abstract Increasing numbers of biomarkers have been identified for various cancers. However, biomarkers associated with endometrial carcinoma (EC) remain largely to be explored. In the current research, we downloaded the RNA-seq data and corresponding clinicopathological features from the Cancer Genome Atlas (TCGA) database. We conducted expression analysis, which resulted in identification of RILPL2 as a novel diagnostic biomarker in EC. The dysregulation of RILPL2 in EC was also validated in multiple datasets. The correlations between clinical features and RILPL2 expression were assessed by logistic regression analysis. Then, Kaplan-Meier analysis, univariate, and multivariate Cox regression analysis were performed to estimate prgnostic values of RILPL2 in the TCGA cohort, which unveiled that increased level of RILPL2 was remarkably associated with better prognosis and could be severd as an independent prognostic biomarker in patients with EC. Moreover, correlation analysis of RILPL2 and tumor-infiltrating immune cells (TIICs) indicated that RILPL2 might play a critical role in regulating immune cell infiltration in EC and is related to immune response. Besides, high methylation level was a significant cause for RILPL2 low expression in EC. Subsequently, weighted gene co-expression network analysis (WGCNA) and enrichment analysis were conducted to explore the RILPL2-involved underlyingl oncogenic mechanisms, and the results indicated that RILPL2 mainly regulated cell cycle. In conclusion, our findings provided evidence that downregulation of RILPL2 in EC is an indicator of adverse prognosis and RILPL2 may act as a promising target for the theraputics of EC.

scholarly journals SURVIVAL ANALYSIS OF PEDIATRIC WILMS TUMOR BASED ON RISK STRATIFICATION

2022 ◽  
Vol 29 (1) ◽  
Author(s):  
Andy ◽  
Yacobda Hamonangan Sigumonrong
Keyword(s):  
Overall Survival ◽  
Regression Analysis ◽  
Prognostic Factors ◽  
Cox Regression ◽  
Wilms Tumor ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Rank Score ◽  
Age Of Diagnosis ◽  
Male Patients

Objective: This study aims to determine prognostic factors of WT patient in Adam Malik Hospital, Medan. Material & Methods: at Adam Malik Hospital, Medan. Univariate and multivariate Cox regression analyses were performed to determine independent prognostic factors for WT. The primary endpoint of this study were patients’ overall survival (OS) obtained by performing Kaplan-Meier analysis on significant variables. Results: From the univariate Cox regression analysis, gender was found to be the sole significant factor (HR = 0.218, p = 0.005) with males have a higher hazard ratio. The multivariate Cox regression analysis yielded age of diagnosis (HR = 13.860, p = 0.014) and incomplete tumor removals (HR = 0.056, p = 0.008). Kaplan-Meier analysis were performed on three significant variables mentioned before. Only gender yielded a significant Mantel-Cox log-rank score (p = 0.002) with male patients were found to have better survivability (which median survival 476 days compared to females’ 11 days). The survival of the boys was 45.45% while all of the girls did not survive until the cut-off. Conclusion: Three prognostic factors, including children’s gender, age of diagnosis, and tumor removal status, were confirmed to be prognostic factors for the overall survival of children with WT. Further studies covering broader demographic areas were suggested to confirm significant results.  

Prognostic role of aberrant mTOR activation in patients with stage II and III colorectal cancer

2020 ◽  
Vol 14 (12) ◽  
pp. 1127-1137
Author(s):  
Tong-Tong Zhang ◽  
Yi-Qing Zhu ◽  
Hong-Qing Cai ◽  
Jun-Wen Zheng ◽  
Jia-Jie Hao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Poor Prognostic Factor ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Risk Predictor

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan–Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.

scholarly journals Identification of Prognostic RBPs in Osteosarcoma

2021 ◽  
Vol 20 ◽  
pp. 153303382110049
Author(s):  
Bei Li ◽  
Long Fang ◽  
Baolong Wang ◽  
Zengkun Yang ◽  
Tingbao Zhao
Keyword(s):  
Regression Analysis ◽  
Prognostic Factors ◽  
Differential Expression ◽  
Ribosome Biogenesis ◽  
Rna Binding ◽  
Cox Regression ◽  
Rna Binding Proteins ◽  
Malignant Tumors ◽  
Differential Expression Analysis ◽  
Cox Regression Analysis

Osteosarcoma often occurs in children and adolescents and causes poor prognosis. The role of RNA-binding proteins (RBPs) in malignant tumors has been elucidated in recent years. Our study aims to identify key RBPs in osteosarcoma that could be prognostic factors and treatment targets. GSE33382 dataset was downloaded from Gene Expression Omnibus (GEO) database. RBPs extraction and differential expression analysis was performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to explore the biological function of differential expression RBPs. Moreover, we constructed Protein-protein interaction (PPI) network and obtained key modules. Key RBPs were identified by univariate Cox regression analysis and multiple stepwise Cox regression analysis combined with the clinical information from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Risk score model was generated and validated by GSE16091 dataset. A total of 38 differential expression RBPs was identified. Go and KEGG results indicated these RBPs were significantly involved in ribosome biogenesis and mRNA surveillance pathway. COX regression analysis showed DDX24, DDX21, WARS and IGF2BP2 could be prognostic factors in osteosarcoma. Spearman’s correlation analysis suggested that WARS might be important in osteosarcoma immune infiltration. In conclusion, DDX24, DDX21, WARS and IGF2BP2 might play key role in osteosarcoma, which could be therapuetic targets for osteosarcoma treatment.

The Role of Surgery in IDH-Wild-Type Lower-Grade Gliomas: Threshold at a High Extent of Resection Should be Pursued

Neurosurgery ◽  
2021 ◽  
Author(s):  
Peng Wang ◽  
Chen Luo ◽  
Peng-jie Hong ◽  
Wen-ting Rui ◽  
Shuai Wu
Keyword(s):  
Cox Regression ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Lower Grade ◽  
Wild Type ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Lower Grade Glioma ◽  
Clinical Benefits

Abstract BACKGROUND While maximizing extent of resection (EOR) is associated with longer survival in lower-grade glioma (LGG) patients, the number of cases remains insufficient in determining a EOR threshold to elucidate the clinical benefits, especially in IDH-wild-type LGG patients. OBJECTIVE To identify the effects of EOR on the survival outcomes of IDH-wild-type LGG patients. METHODS IDH-wild-type LGG patients were retrospectively reviewed. The effect of EOR and other predictor variables on overall survival (OS) and progression-free survival (PFS) was analyzed using Cox regression models and the Kaplan-Meier method. RESULTS A total of 94 patients (median OS: 48.9 mo; median follow-up: 30.6 mo) were included in this study. In the multivariable Cox regression analysis, postoperative residual volume was associated with prolonged OS (HR = 2.238; 95% confidence interval [CI], 1.130-4.435; P = .021) and PFS (HR = 2.075; 95% CI, 1.113-3.869; P = .022). Thresholds at a minimum EOR of 97.0% or a maximum residue of 3.0 cm3 were necessary to impact OS positively. For the telomerase reverse transcriptase (TERT)p-wild-type group, such an association was absent. Significant differences in survival existed between the TERTp-wild-type and mutant patients who underwent relatively incomplete resections (residual ≥2.0 cm3 + TERTp wild type: median OS of 62.6 mo [95% CI: 39.7-85.5 mo]; residual ≥2.0 cm3 + TERTp mutant: median OS of 20.0 mo [95% CI:14.6-25.4 mo]). CONCLUSION Our results support the core role of maximal safe resection in the treatment of IDH-wild-type LGGs, especially for IDH-wild-type + TERTp-mutant LGGs. Importantly, the survival benefits of surgery could only be elucidated at a high EOR cut-off point.

scholarly journals Prognostic Significance of PD-L1 and mTOR Expression in Oral Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Nattinee Charoen ◽  
Kitti Jantharapattana ◽  
Paramee Thongsuksai
Keyword(s):  
Squamous Cell Carcinoma ◽  
Regression Analysis ◽  
Prognostic Factors ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cox Regression ◽  
Prognostic Significance ◽  
P Value ◽  
Cox Regression Analysis

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.

scholarly journals Identification and Analysis of Three Hub Prognostic Genes Related to Osteosarcoma Metastasis

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Jianye Tan ◽  
Haofeng Liang ◽  
Bingsheng Yang ◽  
Shuang Zhu ◽  
Guofeng Wu ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cox Regression ◽  
Survival Rates ◽  
Prognostic Biomarkers ◽  
Messenger Rnas ◽  
Hub Genes ◽  
Cox Regression Analysis ◽  
Expression Levels ◽  
Kaplan Meier ◽  
Before And After

Osteosarcoma (OS) often occurs in children and often undergoes metastasis, resulting in lower survival rates. Information on the complexity and pathogenic mechanism of OS is limited, and thus, the development of treatments involving alternative molecular and genetic targets is hampered. We categorized transcriptome data into metastasis and nonmetastasis groups, and 400 differential RNAs (230 messenger RNAs (mRNAs) and 170 long noncoding RNAs (lncRNAs)) were obtained by the edgeR package. Prognostic genes were identified by performing univariate Cox regression analysis and the Kaplan–Meier (KM) survival analysis. We then examined the correlation between the expression level of prognostic lncRNAs and mRNAs. Furthermore, microRNAs (miRNAs) corresponding to the coexpression of lncRNA-mRNA was predicted, which was used to construct a competitive endogenous RNA (ceRNA) regulatory network. Finally, multivariate Cox proportional risk regression analysis was used to identify hub prognostic genes. Three hub prognostic genes (ABCG8, LOXL4, and PDE1B) were identified as potential prognostic biomarkers and therapeutic targets for OS. Furthermore, transcriptions factors (TFs) (DBP, ESX1, FOS, FOXI1, MEF2C, NFE2, and OTX2) and lncRNAs (RP11-357H14.16, RP11-284N8.3, and RP11-629G13.1) that were able to affect the expression levels of genes before and after transcription were found to regulate the prognostic hub genes. In addition, we identified drugs related to the prognostic hub genes, which may have potential clinical applications. Immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR) confirmed that the expression levels of ABCG8, LOXL4, and PDE1B coincided with the results of bioinformatics analysis. Moreover, the relationship between the hub prognostic gene expression and patient prognosis was also validated. Our study elucidated the roles of three novel prognostic biomarkers in the pathogenesis of OS as well as presenting a potential clinical treatment for OS.

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