Upregulation of ARNTL2 Predicts Poor Survival for Clear Cell Renal Cell Carcinoma and Explores its Associations with PD-L1 and Immune Infiltration

2021 ◽  
Author(s):  
Song Wang ◽  
Xueyou Ma ◽  
Yufan Ying ◽  
Jiazhu Sun ◽  
Zitong Yang ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Tumor Immunity ◽  
Cox Regression ◽  
Immune Escape ◽  
Survival Curve ◽  
Regression Analyses ◽  
Immune Infiltration ◽  
Ccrcc Patient ◽  
Pan Cancer

Abstract Background: Aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2) pertain to the PAS superfamily. Emerging evidences have demonstrated the carcinogenic roles of transcription factor ARNTL2 in human malignancies, while its roles in ccRCC remain elusive. We sought to explore the comprehensive roles of ARNTL2 in ccRCC and place major emphasis on its correlations with tumor immunity.Methods: The available data from GEO, TCGA and GTEx database were combined with our ccRCC patient tissues to verify the upregulation of ARNTL2, Kaplan–Meier survival curve analysis, Cox regression analyses (including univariate and multivariate) were utilized to evaluate the prognostic values of ARNTL2, the potential biological mechanisms of ARNTL2 were analyzed by using GSEA method. The ssGSEA and xCell algorithm were employed to assess the correlations of ARNTL2 expression with tumor immune microenvironment (TIME), The spearman analyses were applied to investigate the relationships between ARNTL2 expression and the tumor mutational burden (TMB), PD-L1 expression and microsatellite instability (MSI) in pan-cancer.Results: ARNTL2 was overexpressed in ccRCC and increased ARNTL2 expression strongly linked to advanced clinical stage and unfavorable overall survival. ARNTL2 was recognized as an independent prognostic marker through cox regression analyses. A prognostic nomogram was subsequently constructed to predict 1-, 3- and 5-year overall survival via integrating ARNTL2 expression with other clinicopathologic variables. GSEA analysis revealed that the focal adhesion, T cell receptor, cell cycle and JAK-STAT signaling pathway were remarkably enriched in high ARNTL2 samples. xCell analysis suggested that high expression of ARNTL2 exhibited an immune infiltration status similar to CD8+ inflamed ccRCC subtype, which characterized by a high infiltration level of CD8+ T cell and elevated expression level of the immune escape biomarkers such as PD-L1, PD-L2, PD1 and CTLA4. Further pan-cancer analysis indicated that ARNTL2 was tightly linked to TMB, MSI, PD-L1 expression, tumor immunity and poor OS in diverse cancer types.Conclusions: ARNTL2 is an independent adverse predictor of ccRCC patient survival and tightly linked to TMB, MSI, PD-L1 expression and immunity.

Extent of lymph node resection and effect on pancreatic cancer overall survival.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 682-682
Author(s):  
Brian Cox ◽  
Nicholas Manguso ◽  
Humair Quadri ◽  
Jessica Crystal ◽  
Katelyn Mae Atkins ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Logistic Regression ◽  
Lymph Node ◽  
Cox Regression ◽  
Survival Curve ◽  
Regression Analyses ◽  
Kaplan Meier ◽  
The Impact ◽  
Meier Survival Curve

682 Background: Lymph node (LN) metastases affect overall survival (OS) in pancreatic cancer (PC). However, a LN sampling threshold does not exist. We examined the impact of nodal sampling on overall survival (OS). Methods: Patients with Stage I-III PC ≥55 years old who underwent curative resection from 2004-2016 were identified from the National Cancer Database (NCDB). After adjusting for age, gender, grade, stage, and Charlson-Deyo score, multiple binomial logistic regression analyses assessed the impact of the LN ratio (LNR) on OS. LNR was defined as the number of positive LN over the number of LN examined. Regression analyses, a Cox-Regression, and a Kaplan-Meier survival curve assessed how many LN should be sampled. Results: A total of 13,673 patients, median age 69 years (55-90), were included. Most were Caucasian (86.6%) males with Charlson-Deyo scores ≤ 1 (90.3%) and moderately to poorly differentiated PC (90.1%). Median number of LN examined was 15 (1-75) with a median of 1 positive LN (0-35). As expected, increased number of positive LNs was associated with reduced OS, p < 0.001. After data normalization, an increasing LNR was associated with a 12-fold likelihood of death [OR: 11.9, p < 0.001 (CI 6.0, 23.7)]. Subsequent regression models established evaluation of ≥ 16 LNs as the greatest predictor of OS. A regression model evaluating < or ≥ 16 lymph nodes was performed to ascertain the effects of age, gender, ethnicity, grade, stage, and LN examined on OS. The logistic regression model correctly classified 74.5% of cases with a specificity of 99.6% (p < 0.001). Examination of < 16 LN, Caucasian race, grade, stage, and higher Charlson-Deyo scores were significantly associated with decreased OS. If ≥ 16 LNs were examined, patients had a 1.5-fold likelihood of better OS, p < 0.001 (CI 1.4, 1.6). An adjusted Cox Regression showed increased HR of 1.2, p < 0.001 (CI 1.1, 1.2) and an unadjusted Kaplan Meier survival curve predicted ≥ 16 LN examined are associated with an increase in OS of 2.8 months [log-rank: 32.0, p < 0.001]. Conclusions: Patients undergoing curative intent resection for PC should have adequate nodal sampling. Stratification of patients by LNR may provide useful information of OS. Examination of ≥ 16 LNs impacts OS in patients with Stage I-III PC.

scholarly journals A novel 10 glycolysis-related genes signature could predict overall survival for clear cell renal cell carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qianwei Xing ◽  
Tengyue Zeng ◽  
Shouyong Liu ◽  
Hong Cheng ◽  
Limin Ma ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Regression Analyses ◽  
Cell Renal Cell Carcinoma

Abstract Background The role of glycolysis in tumorigenesis has received increasing attention and multiple glycolysis-related genes (GRGs) have been proven to be associated with tumor metastasis. Hence, we aimed to construct a prognostic signature based on GRGs for clear cell renal cell carcinoma (ccRCC) and to explore its relationships with immune infiltration. Methods Clinical information and RNA-sequencing data of ccRCC were obtained from The Cancer Genome Atlas (TCGA) and ArrayExpress datasets. Key GRGs were finally selected through univariate COX, LASSO and multivariate COX regression analyses. External and internal verifications were further carried out to verify our established signature. Results Finally, 10 GRGs including ANKZF1, CD44, CHST6, HS6ST2, IDUA, KIF20A, NDST3, PLOD2, VCAN, FBP1 were selected out and utilized to establish a novel signature. Compared with the low-risk group, ccRCC patients in high-risk groups showed a lower overall survival (OS) rate (P = 5.548Ee-13) and its AUCs based on our established signature were all above 0.70. Univariate/multivariate Cox regression analyses further proved that this signature could serve as an independent prognostic factor (all P < 0.05). Moreover, prognostic nomograms were also created to find out the associations between the established signature, clinical factors and OS for ccRCC in both the TCGA and ArrayExpress cohorts. All results remained consistent after external and internal verification. Besides, nine out of 21 tumor-infiltrating immune cells (TIICs) were highly related to high- and low- risk ccRCC patients stratified by our established signature. Conclusions A novel signature based on 10 prognostic GRGs was successfully established and verified externally and internally for predicting OS of ccRCC, helping clinicians better and more intuitively predict patients’ survival.

scholarly journals Identification of a Liver Progenitor Cell-Related Genes Signature Predicting Overall Survival for Hepatocellular Carcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382110414
Author(s):  
Xiaoyong Li ◽  
Jiaqong Lin ◽  
Yuguo pan ◽  
Peng Cui ◽  
Jintang Xia
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Regression Analysis ◽  
Prognostic Model ◽  
Cox Regression ◽  
Risk Group ◽  
Gene Signature ◽  
Regression Analyses ◽  
Related Gene ◽  
Cox Regression Analysis

Background: Liver progenitor cells (LPCs) play significant roles in the development and progression of hepatocellular carcinoma (HCC). However, no studies on the value of LPC-related genes for evaluating HCC prognosis exist. We developed a gene signature of LPC-related genes for prognostication in HCC. Methods: To identify LPC-related genes, we analyzed mRNA expression arrays from a dataset (GSE57812 & GSE 37071) containing LPCs, mature hepatocytes, and embryonic stem cell samples. HCC RNA-Seq data from The Cancer Genome Atlas (TCGA) were used to explore the differentially expressed genes (DEGs) related to prognosis through DEG analysis and univariate Cox regression analysis. Lasso and multivariate Cox regression analyses were performed to construct the LPC-related gene prognostic model in the TCGA training dataset. This model was validated in the TCGA testing set and an external dataset (International Cancer Genome Consortium [ICGC] dataset). Finally, we investigated the relationship between this prognostic model with tumor-node-metastasis stage, tumor grade, and vascular invasion of HCC. Results: Overall, 1770 genes were identified as LPC-related genes, of which 92 genes were identified as DEGs in HCC tissues compared with normal tissues. Furthermore, we randomly assigned patients from the TCGA dataset to the training and testing cohorts. Twenty-six DEGs correlated with overall survival (OS) in the univariate Cox regression analysis. Lasso and multivariate Cox regression analyses were performed in the TCGA training set, and a 3-gene signature was constructed to stratify patients into 2 risk groups: high-risk and low-risk. Patients in the high-risk group had significantly lower OS than those in the low-risk group. Receiver operating characteristic curve analysis confirmed the signature's predictive capacity. Moreover, the risk score was confirmed to be an independent predictor for patients with HCC. Conclusion: We demonstrated that the LPC-related gene signature can be used for prognostication in HCC. Thus, targeting LPCs may serve as a therapeutic alternative for HCC.

scholarly journals Identification and Validation of an 11-Ferroptosis Related Gene Signature and Its Correlation With Immune Checkpoint Molecules in Glioma

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhuohui Chen ◽  
Tong Wu ◽  
Zhouyi Yan ◽  
Mengqi Zhang
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Gene Signature ◽  
Curve Analysis ◽  
Regression Analyses ◽  
Related Gene ◽  
Roc Curve Analysis ◽  
Small Molecule Drugs ◽  
The Relationship ◽  
Genome Atlas

BackgroundGlioma is the most common primary malignant brain tumor with significant mortality and morbidity. Ferroptosis, a novel form of programmed cell death (PCD), is critically involved in tumorigenesis, progression and metastatic processes.MethodsWe revealed the relationship between ferroptosis-related genes and glioma by analyzing the mRNA expression profiles from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), GSE16011, and the Repository of Molecular Brain Neoplasia Data (REMBRANDT) datasets. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to construct a ferroptosis-associated gene signature in the TCGA cohort. Glioma patients from the CGGA, GSE16011, and REMBRANDT cohorts were used to validate the efficacy of the signature. Receiver operating characteristic (ROC) curve analysis was applied to measure the predictive performance of the risk score for overall survival (OS). Univariate and multivariate Cox regression analyses of the 11-gene signature were performed to determine whether the ability of the prognostic signature in predicting OS was independent. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to identify the potential biological functions and pathways of the signature. Subsequently, we performed single sample gene set enrichment analysis (ssGSEA) to explore the correlation between risk scores and immune status. Finally, seven putative small molecule drugs were predicted by Connectivity Map.ResultsThe 11-gene signature was identified to divide patients into two risk groups. ROC curve analysis indicated the 11-gene signature as a potential diagnostic factor in glioma patients. Multivariate Cox regression analyses showed that the risk score was an independent predictive factor for overall survival. Functional analysis revealed that genes were enriched in iron-related molecular functions and immune-related biological processes. The results of ssGSEA indicated that the 11-gene signature was correlated with the initiation and progression of glioma. The small molecule drugs we selected showed significant potential to be used as putative drugs.Conclusionwe identified a novel ferroptosis-related gene signature for prognostic prediction in glioma patients and revealed the relationship between ferroptosis-related genes and immune checkpoint molecules.

A National Cancer Database analysis of the patterns of care for meningeal melanocytoma

2021 ◽  
Author(s):  
Amanda C Tep ◽  
Patrick D Kelly ◽  
Daphne B Scarpelli ◽  
Bailey Bergue ◽  
Shearwood McClelland III ◽  
...  
Keyword(s):  
Overall Survival ◽  
Patient Outcomes ◽  
Cox Regression ◽  
Treatment Patterns ◽  
National Cancer Database ◽  
Regression Analyses ◽  
Database Analysis ◽  
Meningeal Melanocytoma ◽  
Kaplan Meier ◽  
Poor Treatment

Aim: To evaluate demographics, treatment patterns, radiotherapy utilization and patient outcomes in meningeal melanocytomas. Materials & methods: The National Cancer Database was queried for meningeal melanocytomas diagnosed in 2002–2016. The effects of demographic, clinical and treatment variables were determined via Kaplan–Meier log-rank and Cox regression analyses. Results: The median and 5-year overall survival were 57.46 months and 48%, respectively. Patients earning ≥ $48K showed improved survival (p = 0.0319). Radiotherapy and chemotherapy were utilized in 37.7 and 9% of patients, respectively. Conclusion: Income significantly affected survival. Surgery remains the mainstay approach. Radiotherapy was delivered in more than one-third of patients but did not impact survival. However, further analyses were limited by poor treatment modality information in the database.

scholarly journals Impact of Decorin on the Physical Function and Prognosis of Patients with Hepatocellular Carcinoma

2020 ◽  
Vol 9 (4) ◽  
pp. 936
Author(s):  
Takumi Kawaguchi ◽  
Sachiyo Yoshio ◽  
Yuzuru Sakamoto ◽  
Ryuki Hashida ◽  
Shunji Koya ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Physical Function ◽  
Transcatheter Arterial Chemoembolization ◽  
Cox Regression ◽  
Walking Distance ◽  
Regression Analyses ◽  
Multivariate Correlation ◽  
Arterial Chemoembolization

The outcome of patients with hepatocellular carcinoma (HCC) is still poor. Decorin is a small leucine-rich proteoglycan, which exerts antiproliferative and antiangiogenic properties in vitro. We aimed to investigate the associations of decorin with physical function and prognosis in patients with HCC. We enrolled 65 patients with HCC treated with transcatheter arterial chemoembolization (median age, 75 years; female/male, 25/40). Serum decorin levels were measured using enzyme-linked immunosorbent assays; patients were classified into the High or Low decorin groups by median levels. Associations of decorin with physical function and prognosis were evaluated by multivariate correlation and Cox regression analyses, respectively. Age and skeletal muscle indices were not significantly different between the High and Low decorin groups. In the High decorin group, the 6-min walking distance was significantly longer than the Low decorin group and was significantly correlated with serum decorin levels (r = 0.2927, p = 0.0353). In multivariate analysis, the High decorin group was independently associated with overall survival (hazard ratio 2.808, 95% confidence interval 1.016–8.018, p = 0.0498). In the High decorin group, overall survival rate was significantly higher than in the Low decorin group (median 732 days vs. 463 days, p = 0.010). In conclusion, decorin may be associated with physical function and prognosis in patients with HCC.

scholarly journals Interplay of tRNA-Derived Fragments and T Cell Activation in Breast Cancer Patient Survival

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2230 ◽  
Author(s):  
Nayang Shan ◽  
Ningshan Li ◽  
Qile Dai ◽  
Lin Hou ◽  
Xiting Yan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
T Cell ◽  
Cancer Patient ◽  
Breast Cancer Patient ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cox Regression ◽  
Patient Survival ◽  
Significant Difference

Effector CD8+ T cell activation and its cytotoxic function are positively correlated with improved survival in breast cancer. tRNA-derived fragments (tRFs) have recently been found to be involved in gene regulation in cancer progression. However, it is unclear how interactions between expression of tRFs and T cell activation affect breast cancer patient survival. We used Kaplan–Meier survival and multivariate Cox regression models to evaluate the effect of interactions between expression of tRFs and T cell activation on survival in 1081 breast cancer patients. Spearman correlation analysis and weighted gene co-expression network analysis were conducted to identify genes and pathways that were associated with tRFs. tRFdb-5024a, 5P_tRNA-Leu-CAA-4-1, and ts-49 were positively associated with overall survival, while ts-34 and ts-58 were negatively associated with overall survival. Significant interactions were detected between T cell activation and ts-34 and ts-49. In the T cell exhaustion group, patients with a low level of ts-34 or a high level of ts-49 showed improved survival. In contrast, there was no significant difference in the activation group. Breast cancer related pathways were identified for the five tRFs. In conclusion, the identified five tRFs associated with overall survival may serve as therapeutic targets and improve immunotherapy in breast cancer.

scholarly journals Crosstalk between Activated and Inactivated c-Src in Hepatocellular Carcinoma

2011 ◽  
Vol 30 (6) ◽  
pp. 325-333 ◽  
Author(s):  
Mei-Lin Chen ◽  
Chee-Yin Chai ◽  
Kun-Tu Yeh ◽  
Shen-Nien Wang ◽  
Chia-Jung Tsai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Survival Rate ◽  
Cox Regression ◽  
Patient Survival ◽  
Survival Curve ◽  
Clinicopathological Characteristics ◽  
Active State ◽  
Overall Survival Rate ◽  
Independent Prognostic Marker

C-Src activity is regulated by tyrosine phosphorylation at two distinct sites, Tyr416 and Tyr527, with opposite effects. However, the clinical roles of these sites in human cancers are not well defined. This study aims to determine whether the alterations and crosstalk of these two sites may contribute to hepatocellular carcinoma (HCC). Specimens from 85 patients who had undergone curative hepatectomy were collected for this study. The patterns of p-Tyr416-Src and p-Tyr527-Src, as well as the non-phosphorylated status for each site, were determined using immunohistochemistry and statistically correlated with clinicopathological characteristics and overall survival rate. The active state of c-Src, p-Tyr416-c-Src, was positively correlated with tumour grade (P= 0.062) but inversely correlated with vascular invasion (P= 0.071). Its non-phosphorylated status, non-p-Tyr416-c-Src, was positively correlated with tumour stage and grade (P= 0.041 and 0.020). The inactive state of c-Src, p-Tyr527-c-Src, was decreased in male patients but increased HCV-infected patients (P= 0.044 and 0.033). The Kaplan-Meier survival curve further showed that increased p-Tyr416-c-Src and decreased non-p-Tyr527-c-Src expression were associated with a poor patient survival rate (P= 0.004 and 0.025). Interestingly, the expression of non-p-Tyr416-c-Src was positively correlated with that of p-Tyr527-c-Src in the HCC lesions (P= 0.040). In addition, the patients with concomitantly low p-Tyr416-c-Src and non-p-Tyr527-c-Src expression had a prolonged overall survival rate (P= 0.030). A multivariable COX regression model showed that p-Tyr416-c-Src expression was an effective predictor for patient survival in HCC [OR = 3.78, 95%CI = 1.46–9.76;P= 0.006]. Our results suggest that the active state of c-Src, p-Tyr416-c-Src, may serve as an independent prognostic marker of patient survival in HCC. Relative levels of other phosphorylated or non-phosphorylated c-Src kinases may also present different statuses during HCC development and require further investigation.

Hypercvad for Treatment of Adult Acute Lymphocytic Leukemia: The Moffitt Cancer Center Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4241-4241
Author(s):  
Kendra L. Sweet ◽  
Robert M. Crescentini ◽  
Jennifer L. Cultrera ◽  
Jeffrey E Lancet ◽  
Rami S. Komrokji
Keyword(s):  
Overall Survival ◽  
Regression Analysis ◽  
T Cell ◽  
Acute Lymphocytic Leukemia ◽  
Cox Regression ◽  
Philadelphia Chromosome ◽  
Lymphocytic Leukemia ◽  
Cancer Center ◽  
Cox Regression Analysis ◽  
Frontline Therapy

Abstract 4241 Background: Acute lymphocytic leukemia (ALL) incidence is approximately 4000 cases per year in the USA. Several standard induction regimens are used upfront for the treatment of ALL. The HyperCVAD regimen is currently a widely used upfront treatment option for adult ALL patients based on pioneer work at MD Anderson Cancer Center (MDACC). Here we present our experience with the HyperCVAD regimen treating ALL at Moffitt Cancer Center (MCC), representing the largest cohort treated with this regimen outside MDACC. Methods: Patients who were diagnosed and treated at MCC with ALL were identified through the MCC Total Cancer Care database. Individual charts were reviewed. All patients treated with the HyperCVAD regimen frontline were included in this analysis. The HyperCVAD regimen was administered as originally described at MDACC. Philadelphia positive patients were treated with addition of tyrosine kinase inhibitors (TKI) (imatinib or dasatinib). Descriptive data are reported, t-test was used to compare continuous variables, chi square test for categorical variables, Kaplan Meier curves were used for overall survival (OS). Log rank test was used to compare survival times between groups. Cox regression analysis was used for multivariable analysis. All analyses were conducted using SPSS version 19.0 Results: Between 1/1/2002 and 6/30/2011, 100 ALL patients were treated with HyperCVAD at MCC. The median age was 45 years (range 18–83), 26 were above age of 60 years and 26 were below age of 30 years. Sixty three percent were male and 37% were female. Sixty five percent were white, 6% were African America, 7% were Hispanic and 22% were described as other. B-Cell ALL accounted for 83% of patients, while the other 17% had T-Cell origin. Of the 100 patients, 23% of patients were Philadelphia chromosome positive, while 72% were negative, and in 5% karyotype was unknown. Splenomegaly was present at diagnosis in 18% of patients, while 17% presented with lymphadenopathy. Twenty-three percent of patients presented with a WBC of 50,000 or greater. CNS disease was noted in 9% of patients at diagnosis. Seventy-six percent achieved a complete response (CR), while 12% had refractory disease. Response to frontline was not documented in 12% of patients. The median overall survival was 27 months (95% CI 15.6–38.3). In univariable analysis, no difference in outcome was observed based on gender, race, Philadelphia chromosome positivity, B or T-cell origin, presence of lymphadenopathy, splenomegaly, WBC >50,000 or CNS disease at presentation. Age was a significant prognostic factor. The median OS for patients <60 years old was 34 months (95% CI 20.8–47.), and 16 months for patients >60 years old (95% CI 6.9–25.1) (p= 0.006) (figure-1) The median OS was higher in patients who achieved CR with frontline chemotherapy. OS was 34 months (95% CI 22.5–45.4) compared to 13 months in patients who did not achieve CR after frontline (95% CI 7.3–18.7) (p=< 0.005). Thirty-eight patients proceeded to allogeneic SCT. The median OS was 40 months in patients who proceeded to allogeneic SCT compared with 16 months in patients who did not (p=0.002). In Cox regression analysis, achieving CR with frontline induction, and allogeneic SCT were statistically significant independent variables for OS for adult patients with ALL. The odds ratio was 3.4 in patients achieving CR with frontline therapy, and 3.1 in patients who underwent allogeneic SCT. Conclusion: To our knowledge, this cohort represents the largest group of ALL patients treated outside MDACC with HyperCVAD based regimens, with similar overall results in the setting of tertiary centers. Achievement of CR after frontline therapy, and undergoing allogeneic SCT were statistically significant prognostic indicators. The outcome of elderly patients (age >60) was inferior. In the elderly population there were lower rates of CR and less number of patients proceeded to allogeneic SCT. The outcome in Philadelphia chromosome positive ALL has improved with the introduction of TKI’s and allogeneic SCT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Landscape of Glycosyltransferase Gene Signature for Overall Survival Prediction in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Qiang Cai ◽  
Shizhe Yu ◽  
Jian Zhao ◽  
Duo Ma ◽  
Long Jiang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Risk Score ◽  
Prognostic Value ◽  
Cox Regression ◽  
Risk Groups ◽  
Gene Signature ◽  
Low Risk ◽  
Regression Analyses ◽  
Risk Patients

Abstract Background: Hepatocellular carcinoma (HCC) is heterogeneous disease occurring in the background of chronic liver diseases. The role of glycosyltransferase (GT) genes have recently been the focus of research associating with the development of tumors. However, the prognostic value of GT genes in HCC remains not elucidated. This study aimed to demonstrate the GT genes related to the prognosis of HCC through bioinformatics analysis.Methods: The GT genes signatures were identified from the training set of The Cancer Genome Atlas (TCGA) dataset using univariate and the least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Then, we analyzed the prognostic value of GT genes signatures related to the overall survival (OS) of HCC patients. A prognostic model was constructed, and the risk score of each patient was calculated as formula, which divided HCC patients into high- and low-risk groups. Kaplan-Meier (K-M) and Receiver operating characteristic (ROC) curves were used to assess the OS of HCC patients. The prognostic value of GT genes signatures was further investigated in the validation set of TCGA database. Univariate and multivariate Cox regression analyses were performed to demonstrate the independent factors on OS. Finally, we utilized the gene set enrichment analysis (GSEA) to annotate the function of these genes between the two risk categories. Results: In this study, we identified and validated 4 GT genes as the prognostic signatures. The K-M analysis showed that the survival rate of the high-risk patients was significantly lower than that of the low-risk patients. The risk score calculated with 4 gene signatures could predict OS for 3-, 5-, and 7-year in patients with HCC, revealing the prognostic ability of these gene signature. In addition, Multivariate Cox regression analyses indicated that the risk score was an independent prognostic factor for HCC. Functional analysis further revealed that immune-related pathways were enriched, and immune status in HCC were different between the two risk groups.Conclusion: In conclusion, a novel GT genes signature can be used for prognostic prediction in HCC. Thus, targeting GT genes may be a therapeutic alternative for HCC.

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