scholarly journals BDP1 Variants I1264M and V1347M Significantly Associated with Clinical Outcomes of Pediatric Neuroblastoma Patients Imply a New Prognostic Biomarker: A 121-Patient Cancer Genome Study

Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2364
Author(s):  
Xiaoqing Li ◽  
Lan Sun ◽  
Andres Stucky ◽  
Lingli Tu ◽  
Jin Cai ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Gene Mutations ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Genome Study ◽  
Cancer Genome Atlas

Background: Neuroblastoma (N.B.) is the most common tumor in children. The gene BDP1 (B Double Prime 1) plays a role in cancers but is less known in N.B. Thus, we conducted this study to investigate the value of BDP1 mutations in N.B. prognosis. Methods: A dataset of 121 NB patients from the Cancer Genome Atlas database was used to analyze BDP1 gene mutations by RNA sequencing. Kaplan-Meier estimates were performed for overall survival (O.S.) analysis on BDP1 variants, and Cox’s proportional hazards regression model was used for multivariate analysis. Results: In 121 NB patients, we identified two variants of BDP1 associated with N.B., located at chr5:71511131 and chr5:71510884. The prevalence of these BDP1 variants, I1264M and V1347M, was 52.9% (64/121) and 45.5% (55/121), respectively. O.S. analysis showed a significant difference between subgroups with or without BDP1 variants (p < 0.05). Multivariate analysis further revealed that BDP1ariants were independent prognostic variables in N.B. (p < 0.05). Conclusion: Our results suggest BDP1 variants are associated with significantly improved clinical outcomes in N.B., thus providing clinicians with a new tool.

High KIF11 expression is associated with poor outcome of NSCLC

2021 ◽  
pp. 030089162098834
Author(s):  
Junhui Liu ◽  
Yubin Tian ◽  
Lei Yi ◽  
Zhaojia Gao ◽  
Ming Lou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Tissue Microarrays ◽  
The Cancer Genome Atlas ◽  
Normal Lung ◽  
Clinicopathologic Characteristics ◽  
Poor Outcome ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Cancer Genome Atlas

Purpose: To clarify the correlation between KIF11 (kinesin family member 11) and clinicopathologic characteristics of non-small cell lung cancer (NSCLC) and identify the prognostic value of KIF11 in patients with NSCLC. Methods: For investigating the expression of KIF11 in NSCLC, two tissue microarrays (TMAs: one contained 60 paired NSCLC tissues and paratumor tissues, the other contained 140 NSCLC tissues and 10 normal lung tissues) were constructed, stained, and scored. The Cancer Genome Atlas (TCGA) datasets were used to explore the differential expression level of KIF11 between NSCLC and paratumor. Kaplan-Meier survival curves were plotted and multivariate analysis were carried out. Results: The staining of KIF11 mainly distributed throughout the cytoplasm of tumor cells. Its expression was higher in NSCLC than paratumor cells, and similar results were obtained from TCGA datasets. We found that high expression of KIF11 had a significant correlation with lymph node metastases ( p = 0.024) and pathologic stage ( p = 0.018); that significant difference was not found in any other clinicopathologic characteristic. As univariate and multivariate analysis showed, KIF11 expression was significantly correlated with overall survival time of NSCLC ( p = 0.002, p = 0.025, respectively). High KIF11 expression was found to significantly associate with overall survival of stage II–III ( p = 0.001) and lung adenocarcinoma ( p = 0.036). Conclusion: High KIF11 expression predicts poor outcome in NSCLC. KIF11 is expected to be a viable prognostic biomarker for NSCLC.

Abstract 15467: Impact of Thrombocytopenia on Clinical Outcomes in Atrial Fibrillation Patients With Anemia: The Fushimi Af Registry

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kenjiro Ishigami ◽  
Syuhei Ikeda ◽  
KOSUKE DOI ◽  
Yasuhiro Hamatani ◽  
Akiko Fujino ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Outcomes ◽  
Major Bleeding ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Antithrombotic Drugs ◽  
Prospective Survey ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Independent Determinant

Introduction: Anemia has been reported to be associated with poor prognosis in patients with atrial fibrillation (AF). Concomitant thrombocytopenia (TP) may or may not affect the prescription of antithrombotic drugs and clinical outcomes in these patients. Methods: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto. We defined TP as platelet counts less than 150,000/μL and anemia as hemoglobin less than 11 g/dL. Among 666 patients with anemia, we compared the clinical backgrounds and outcomes of those with TP (n=183) and those without (n=483). Results: Compared with patients without TP, patients with TP were more likely to have chronic kidney disease (75.4% vs. 61.8%, p=0.001), and less likely to have hypertension (58.5% vs. 67.0%, p=0.0393), and less likely to have dyslipidemia (27.3% vs. 38.3%, p=0.0079). Age, sex, body weight, CHADS 2 score, CHA 2 DS 2 -VASc score, HAS-BLED score, and previous major bleeding were comparable between the groups. Furthermore, prescription of anti-thrombotic drugs was comparable (Figure A). On Kaplan-Meier analysis, the incidence of all-cause death was higher in TP group (hazard ratio [HR] 1.52; 95% confidence interval [CI] 1.20-1.91, p<0.05) (Figure B-1). There was no significant difference in other adverse events between patients with and without TP (major bleeding: HR 1.11; 95% CI 0.41-3.31, p=0.8, hospitalization for heart failure: HR 1.11; 95% CI 0.74-1.61, p= 0.61 and stroke or systemic embolism: HR 0.91; 95% CI 0.43-1.78, p=0.80) (Figure B-2, 3, 4). Multivariate Cox proportional hazards regression analysis adjusting for potential confounders revealed that TP was an independent determinant of all-cause death (adjusted HR: 1.41, 95% CI; 1.11-1.78, p=0.006). Conclusions: Concomitant TP in AF patients with anemia did not affect the prescription of antithrombotic drugs, and was independently associated with all-cause death in the Fushimi AF Registry.

Can sidedness predict for survival in primary locoregional colon cancers?

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 584-584
Author(s):  
Weining Wang ◽  
Chin Jin Seo ◽  
Grace Hwei Ching Tan ◽  
Claramae Shulyn Chia ◽  
Khee Chee Soo ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Multivariate Analysis ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Rank Test ◽  
Rectosigmoid Junction ◽  
Colon Cancers ◽  
Kaplan Meier ◽  
Significant Difference ◽  
The Impact

584 Background: Right and left-sided colon cancers are embryonically distinct and present differently. Recently, there has been growing belief that sidedness could be independently associated with survival outcomes. This has important clinical implications regarding the prognostication, management and surveillance of colon cancer patients. Hence, we aim to investigate the impact of sidedness on survival in our patient population in this study. Methods: Patients who had primary treatment naïve colon cancer who underwent curative surgical resection in our institution from September 2002 to December 2010 were included in this study. Demographic and clinicopathological data was collected from electronic records and clinical charts. Tumours arising from the cecum, ascending colon, hepatic flexure and transverse colon were considered right-sided, while those arising from splenic flexure and descending colon were considered left-sided. Cancers of the rectosigmoid junction and rectum were excluded. Kaplan-Meier curves and log-rank test were used to compare overall, locoregional recurrence-free and distant recurrence-free survivals (OS, LRFS, DRFS respectively) between both groups. Multivariate analysis was performed using Cox regression proportional hazards. Results: 389 patients were included in this study. 238 had left-sided tumours while the remaining 151 had right-sided tumours. In our cohort, right-sided tumours were associated with older age and mucinous histology. Kaplan-Meier curves plotted showed improved LRFS in left-sided tumours (p = 0.04, median survival not reached) but no significant difference in OS and DRFS. On multivariate analysis, sidedness was also found to be an independent prognostic factor for LRFS but not OS and DRFS despite factoring in age, size of tumour, pT, pN and histology. Conclusions: Our study suggests that left-sided tumours in primary colon cancer are independently prognostic for improved locoregional survival as compared to the right-sided tumours, even after taking into account other known factors such as age, staging and histology.

scholarly journals The m6A Methylation Gene SNRPC can be used as a Biomarker for the Prognosis and Immunotherapy of Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Jihao Cai ◽  
Minglei Zhou ◽  
Jianxin Xu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Rna Methylation ◽  
Kaplan Meier ◽  
Pathogenic Factors ◽  
Therapeutic Value ◽  
Cancer Genome Atlas ◽  
Checkpoint Inhibitor Therapy ◽  
Genome Consortium

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. Due to its complex pathogenic factors, the prognosis of HCC is poor. Therefore, a credible prognostic biomarker is urgently needed for this disease. N6-methyladenosine (m6A) RNA methylation plays an important role in the tumorigenesis, progression and prognosis of many tumors. However, studies on the prognostic and therapeutic value of this modification in HCC are lacking.Case Presentation: The HCC RNA-seq profiles in The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, including 421 LIHC and 440 LIRI samples respectively, were used in this study. The expressive distinction of 21 RNA methylation regulators between HCC and normal tissue were firstly assessed and SNRPC was obtained. Then the expression of SNRPC was validated as a risk factor for prognosis by Kaplan-Meier analysis and employed to establish a nomogram with T pathologic stage. By GSVA and GSEA analyses, we found SNRPC was mainly related to protein metabolism and immune process. Further, ESTIMATE, MCP-counter and single sample GSEA (ssGSEA) algorithm showed high-SNRPC expression group had lower stromal scores, a lower abundance of endothelial cells, fibroblasts and immune infiltration. Ultimately, Tumor Immune Dysfunction and Exclusion (TIDE) analysis exhibited high-SNRPC expression group showed non-response to immune checkpoint inhibitor therapy, especially to a PD-1 inhibitor.Conclusion: SNRPC could serve as valuable prognostic and immunotherapeutic marker in HCC. We provide here an accurate nomogram for clinical diagnosis using SNRPC as a biomarker.

scholarly journals Characterization of bidirectional gene pairs in The Cancer Genome Atlas (TCGA) dataset

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7107 ◽  
Author(s):  
Juchuanli Tu ◽  
Xiaolu Li ◽  
Jianjun Wang
Keyword(s):  
Gene Pair ◽  
Expression Profiles ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Gene Pairs ◽  
Significant Difference ◽  
Cancer Genome Atlas ◽  
Tcga Dataset ◽  
Bidirectional Gene Pair ◽  
Genome Atlas

The “bidirectional gene pair” indicates a particular head-to-head gene organization in which transcription start sites of two genes are located on opposite strands of genomic DNA within a region of one kb. Despite bidirectional gene pairs are well characterized, little is known about their expression profiles and regulation features in tumorigenesis. We used RNA-seq data from The Cancer Genome Atlas (TCGA) dataset for a systematic analysis of the expression profiles of bidirectional gene pairs in 13 cancer datasets. Gene pairs on the opposite strand with transcription end site distance within one kb or on the same strand with the distance of two genes between 1–10 kb and gene pairs comprising two randomly chosen genes were used as control gene pairs (CG1, CG2, and random). We identified and characterized up-/down-regulated genes by comparing the expression level between tumors and adjacent normal tissues in 13 TCGA datasets. There were no consistently significant difference in the percentage of up-/down-regulated genes between bidirectional and control/random genes in most of TCGA datasets. However, the percentage of bidirectional gene pairs comprising two up- or two down-regulated genes was significantly higher than gene pairs from CG1/2 in 12/11 analyzed TCGA datasets and the random gene pairs in all 13 TCGA datasets. Then we identified the methylation correlated bidirectional genes to explore the regulatory mechanism of bidirectional genes. Like the differentially expressed gene pairs, the bidirectional genes in a pair were significantly prone to be both hypo- or hyper-methylation correlated genes in 12/13 TCGA datasets when comparing to the CG2/random gene pairs despite no significant difference between the percentages of hypo-/hyper-methylation correlated genes in bidirectional and CG2/random genes in most of TCGA datasets. Finally, we explored the correlation between bidirectional genes and patient’s survival, identifying prognostic bidirectional genes and prognostic bidirectional gene pairs in each TCGA dataset. Remarkably, we found a group of prognostic bidirectional gene pairs in which the combination of two protein coding genes with different expression level correlated with different survival prognosis in survival analysis for OS. The percentage of these gene pairs in bidirectional gene pair were significantly higher than the gene pairs in controls in COAD datasets and lower in none of 13 TCGA datasets.

Indoleamine 2,3-dioxygenase (IDO1), PD-L1, and overall survival (OS) of patients diagnosed with esophageal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 50-50 ◽  
Author(s):  
Ari Rosenberg ◽  
Derek Wainwright ◽  
Alfred Rademaker ◽  
Carlos Galvez ◽  
Matthew Genet ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Survival Data ◽  
Human Cancer ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Mrna Levels ◽  
Exact Test ◽  
Kaplan Meier ◽  
Cancer Genome Atlas ◽  
Genome Atlas

50 Background: Immune checkpoint inhibition of PD-L1 is emerging as an important therapeutic target for patients with advanced esophageal cancer. However, response rates to therapy remain low. IDO1 is a rate-limiting immunosuppressive enzyme that has emerged as an important immunotherapeutic target in human cancer. The role, expression pattern, and relevance of IDO1 in esophageal cancer are currently unknown. Here, we utilize gene expression analysis of the cancer genome atlas and quantitative immunohistochemistry (IHC) to understand whether IDO1 contributes to a poor esophageal cancer patient prognosis. Methods: mRNA expression was assessed using Hi-RNA sequencing in an esophageal squamous cell carcinoma (SCC) cohort of 87 patients and an adenocarcinoma (AC) cohort of 97 patients. Survival data was obtained from the Cancer Genome Atlas. Patient survival was analyzed by the Kaplan-Meier Method. IHC for a second cohort of 93 cases of esophageal SCC were stained for IDO1, PD-L1, and CD3ε, followed by light microscopic immunoscoring analysis. Correlation between markers was analyzed using Fisher’s exact test. Results: The median OS for high versus low IDO1 mRNA levels was 15.9 months vs 41.5 months, respectively (p =0.02) in the SCC cohort. The median OS was 20.1 months and 58.6 months in the high vs low IDO1 mRNA levels, respectively (p = 0.036) in the esophageal AC cohort. High co-expression for IDO1 and PD-L1 vs low co-expression of these markers, demonstrated a median OS of 15.1 months and 41.5 months, respectively, in the SCC cohort, and 13.7 months and 41.5 months, respectively, in the AC cohort. IHC for IDO1 SCC showed a significant correlation with PD-L1 (p = < 0.0001) and CD3ε (p = < 0.0001). PD-L1 expression also significantly correlated with CD3ε expression (p = < 0.0001). Conclusions: Esophageal cancer with high IDO1 and PD-L1 levels is associated with significantly decreased survival. The expression of IDO1 and PD-L1 is significantly enhanced by the coincident intratumoral increase of T cells. These data suggest that combinatorial approaches for combination therapies that simultaneously inhibit IDO1 and PD-(L)1 may enhance T-cell mediated control of esophageal cancer in patients.

scholarly journals Association Between Obesity and Incident Colorectal Cancer: An Analysis Based on Colorectal Cancer Database in the Cancer Genome Atlas

2021 ◽  
Author(s):  
Su Yongxian ◽  
Chen Tonghua
Keyword(s):  
Colorectal Cancer ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Obese Group ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Hub Genes ◽  
Significant Difference ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Abstract Background To investigate gene factors of colorectal cancer (CRC) in obesity and potential molecular markers. Methods Clinical data and mRNA expression data from The Cancer Genome Atlas (TCGA) was collected and divided into obese group and non-obese group according to BMI. The differential expressed genes (DEGs) were screened out by “Limma” package of R software based on (|log2(fold change)|>2 and p < 0.05). The functions of DEGs were revealed with Gene Ontology and Kyoto Encyclopedia Genes and Genomes pathway enrichment analysis using the DAVID database. Then STRING database and Cytoscape were used to construct a protein-protein interaction (PPI) network and identify hub genes. Kaplan-Meier analysis was used to assess the potential prognostic genes for CRC patients. Results It has revealed 2055 DEGs in obese group with CRC, 7615 DEGs in non-obese group and 9046 DEGs in total group. MS4A12, TMIGD1, CA2, GBA3 and SLC51B were the top five downregulated genes in obese group. A PPI network consisted of 1042 nodes and 4073 edges, and top ten hub genes SST, PYY, GNG12, CCL13, MCHR2, CCL28, ADCY9, SSTR1, CXCL12 and ADRA2A were identified in obese group. PDCD11 may well predict overall survivals of CRC patients in non-obese group. The survival time of obese group was shorter than that of non-obese group, but there was no significant difference. Conclusions PDCD11 may be a potential molecular marker for non-obese patients with CRC.

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