Correlation between LRP1B Mutations and Tumor Mutation Burden in Gastric Cancer

Background. It has been shown that low-density lipoprotein receptor-related protein 1B (LRP1B) mutations correlate with tumor mutation burden (TMB) and prognosis in patients with melanoma and non-small-cell lung cancer, while the relationship between LRP1B mutations and TMB in gastric cancer needs further study. This study is aimed at exploring the relationship between LRP1B mutations and TMB in gastric cancer. Methods. Mutation frequency profiles of the genes in patients with gastric cancer in TCGA-STAD dataset were analyzed by bioinformatics analysis. The relationship among LRP1B mutations, TMB, and patient clinical features in gastric cancer was investigated by the chi-square test. The TMB prediction capacity based on LRP1B mutation status was evaluated by ROC curves. Results. LRP1B is one of the top 10 genes with high gene mutation frequency in gastric cancer. The mutation status of LRP1B in gastric cancer patients was significantly correlated with age and TP53 and MUC16 mutation status. The result of ROC curve analysis revealed that the mutation status of LRP1B could be considered as an indicator of the degree of TMB in patients with gastric cancer. Conclusion. This study presented the relationship between TMB and LRP1B mutations in gastric cancer, providing a novel perspective for gastric cancer prognosis and therapy.

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The relationship of the serum endocan level with the CHA2DS2-VASc score in patients with paroxysmal atrial fibrillation

The Egyptian Heart Journal ◽

10.1186/s43044-021-00132-1 ◽

2021 ◽

Vol 73 (1) ◽

Author(s):

Gökhan Ceyhun

Keyword(s):

Atrial Fibrillation ◽

Paroxysmal Atrial Fibrillation ◽

Stroke Risk ◽

Low Density Lipoprotein ◽

Multivariate Logistic Regression Analysis ◽

Density Lipoprotein ◽

Roc Curve Analysis ◽

Reactive Protein ◽

Relationship Of ◽

The Relationship

Abstract Background In this study considering the relationship between serum endocan and CHA2DS2-VASc score, we assumed that endocan level could be a new biomarker for stroke risk in patients with paroxysmal atrial fibrillation (PAF). It was examined that endocan could be an alternative to determine the risk of stroke and anticoagulation strategy in patients with PAF. The CHA2DS2-VASc scores were calculated for 192 patients with PAF, and their serum endocan levels were measured. The patients were divided into two groups as those with low to moderate (0-1) and those with high (≥ 2) CHA2DS2-VASc scores, and the endocan levels were compared between these two groups. Results The serum endocan level was significantly higher in the high CHA2DS2-VASc score group (p < 0.001). In the multivariate logistic regression analysis, endocan, C-reactive protein, and low-density lipoprotein were found to be independent determinants of the CHA2DS2-VASc score. The predictive value of endocan was analyzed using the ROC curve analysis, which revealed that endocan predicted a high stroke risk (CHA2DS2-VASc ≥ 2) at 82.5% sensitivity and 71.2% specificity at the cutoff value of 1.342. Conclusion This study indicates that endocan is significantly associated with CHA2DS2-VASc score. We demonstrated that endocan could be a new biomarker for the prediction of a high stroke risk among patients diagnosed with PAF.

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Abstract 6467: Tumor mutation burden combined with tumor markers as predictive prognostic biomarkers for neoadjuvant chemotherapy in patients with gastric cancer

10.1158/1538-7445.am2020-6467 ◽

2020 ◽

Author(s):

Yongning Jia ◽

Honglin Zhu ◽

Fei Pang ◽

Fei Shan ◽

Shuangxi Li ◽

...

Keyword(s):

Gastric Cancer ◽

Neoadjuvant Chemotherapy ◽

Tumor Markers ◽

Prognostic Biomarkers ◽

Tumor Mutation Burden ◽

Mutation Burden

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MUC4 , MUC16 , and TTN genes mutation correlated with prognosis, and predicted tumor mutation burden and immunotherapy efficacy in gastric cancer and pan‐cancer

Clinical and Translational Medicine ◽

10.1002/ctm2.155 ◽

2020 ◽

Vol 10 (4) ◽

Author(s):

Yue Yang ◽

Jieyun Zhang ◽

Yanxing Chen ◽

Ruihua Xu ◽

Qi Zhao ◽

...

Keyword(s):

Gastric Cancer ◽

Tumor Mutation Burden ◽

Mutation Burden ◽

Pan Cancer

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FoundationOne as a relevant tool for comprehensive genomic profiling and assessment of tumor mutation burden in the era of precision oncology in India.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e23096 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e23096-e23096

Author(s):

Amit Verma ◽

Nitesh Rohatgi ◽

Pramod Kumar Julka ◽

Meenu Walia ◽

Ankur Bahl ◽

...

Keyword(s):

Tyrosine Kinases ◽

Mutation Frequency ◽

Unknown Primary ◽

Precision Oncology ◽

Tumor Type ◽

Genomic Profiling ◽

Tumor Mutation Burden ◽

Mutation Burden ◽

Comprehensive Genomic Profiling ◽

Tumor Types

e23096 Background: Comprehensive genomic profiling (CGP) is gaining acceptability globally, but clinical experience in developing countries like India is limited. CGP identifies genomic alterations (GA), with tumor mutation burden (TMB) and microsatellite status (MSI), revealing therapeutic options such as targeted inhibitors and immunotherapies. We sought to evaluate the mutation frequency and actionability across tumors. Methods: Metastatic and/or refractory patients (referred to Personalized Cancer Medicine Clinic) underwent CGP analysis, including calculation of TMB and MSI, using a targeted NGS panel (FoundationOne, 53 samples; FoundationOne Heme, 4 samples). This panel detects all relevant classes of GA: base substitutions, small indels, rearrangements and copy number changes. Mutation frequencies were compared with the larger Foundation database. TMB status was reported as low (≤5 mutations/Mb), intermediate (6-19 mut/Mb) or high (≥20 mut/Mb). Results: The most common tumor types were lung (23%), breast (14%) and sarcoma (12%); other tumor types, including unknown primary constituted the rest (51%). Most samples were from metastatic sites (60%). Oncogenic GA were found in 131 genes across all tumor subtypes and affected major pathways: apoptosis/cell cycle (31%), PI3K (14%), transcriptional regulation (13%), and receptor tyrosine kinases (10%). Among these GA, 38 were considered actionable and were distributed across 43 (75%) samples. Therapies with FDA approval for the tumor type analyzed were indicated for 18 samples; an additional 25 samples had GA associated with therapies FDA approved for another indication. More than 1 actionable GA was identified in 24/43 (56%). TMB status was low in 36 (63%), intermediate in 19 (33%) and high in 2 (3.5%). High TMB status correlated with high MSI status (p < 0.001). Trend observed in the mutation frequency was comparable with the larger Foundation database. Conclusions: This is the first study in India showing CGP identified actionable targets associated with FDA approved therapies in approx. 32% of cases. TMB status identified 2/57 samples with high mutation burden for whom immunotherapy might be relevant.

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CPXM1: a novel biomarker for gastric cancer prognosis

10.21203/rs.3.rs-337128/v1 ◽

2021 ◽

Author(s):

Jun Du ◽

Mengxiang Zhu ◽

Wenwu Yan ◽

Changsheng Yao ◽

Qingyi Li ◽

...

Keyword(s):

Gastric Cancer ◽

Poor Prognosis ◽

The Cancer Genome Atlas ◽

Cancer Prognosis ◽

Signal Pathways ◽

Data Set ◽

Kaplan Meier ◽

Cancer Genome Atlas ◽

Cox Proportional Hazard Regression ◽

The Relationship

Abstract Background The molecular role of carboxypeptidase X, M14 family member (CPXM1) in oncogenesis or tumor progression remains unclear. The aim of this study was to determine whether CPXM1 can be used as a potential prognostic biomarker for gastric cancer (GC). Methods We first demonstrated the relationship between CPXM1 expression and GC in various public databases. Secondly, the expression of CPXM1 in GC tissues was further verified by immunohistochemical staining using tissue microarray containing 96 cases of GC patients. Kaplan–Meier analysis and a Cox proportional hazard regression model were performed to evaluate the relationship between the expression of CPXM1 and the survival of GC patients. Finally, we used the expression data of CPXM1 in The Cancer Genome Atlas database to predict CPXM1-related signaling pathways through bioinformatics analysis. Results The expression level of CPXM1 in GC tissues was significantly correlated with tumor size (p = 0.041) and lymph node metastasis (p = 0.014). In addition, Kaplan–Meier analysis showed that the expression of CPXM1 in GC tissues was significantly associated with poor prognosis (p = 0.011). Multivariate analysis indicated that CPXM1 is a potential predictor of poor prognosis in GC patients (p = 0.026). The results of biosynthesis analysis demonstrated that the data set of CPXM1 high expression was mainly enriched in cancer-related signal pathways. Conclusion CPXM1 is an effective biomarker for the prognosis of GC patients and may play a key role in the occurrence and progression of GC.

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Analysis of Threshold Changes of Tumor Mutation Burden of Gastric Cancer and Its Relationship with Patients’ Prognosis

Journal of Oncology ◽

10.1155/2021/9026610 ◽

2021 ◽

Vol 2021 ◽

pp. 1-5

Author(s):

Nan Zhang ◽

Peiyu Li ◽

Xin Wu ◽

Shaoyou Xia ◽

Xudong Zhao ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Pearson Correlation ◽

Disease Free Survival ◽

Free Survival ◽

Tumor Mutation Burden ◽

D2 Lymph Node Dissection ◽

Logistic Analysis ◽

Mutation Burden ◽

Disease Free

Objective. Gastric cancer is a malignant tumor originating from gastric mucosal epithelium. Here, we aimed to investigate the analysis of the threshold change of gastric cancer tumor mutation burden (TMB) and its relationship with the prognosis of patients. Methods. 256 patients with gastric cancer were selected as subjects. All patients were in the advanced stage and received surgical resection of D2 lymph node dissection. After the operation, a follow-up was performed for 24 months, and the disease-free survival and overall survival of patients were counted. The NGS molecular biological was detected to obtain gastric cancer tumor mutation burden (TMB) data. Pearson correlation analysis software was used to analyze the correlation between TMB threshold and disease-free survival or overall survival of patients with gastric cancer, and the multivariate logistic analysis was performed as well. Results. The disease-free survival period and the overall survival period of patients in the low-to-medium TMB group were both longer than those in the high TMB group. Pearson correlation analysis results showed that the TMB threshold was negatively correlated with the disease-free survival and overall survival of gastric cancer patients. Results from multivariate logistic analysis showed that high TMB thresholds have a greater impact on disease-free survival and overall survival of patients, but the impact of medium and low TMB thresholds on disease-free survival and overall survival of patients is weakened. Conclusions. The TMB threshold level has a predictive effect on the effect of surgical resection of D2 lymph node dissection, and high levels of TMB can significantly affect disease-free survival and overall survival of patients with advanced gastric cancer.

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Expressivity of Interleukin-8 and Gastric Cancer Prognosis Susceptibility: A Systematic Review and Meta-Analysis

Dose-Response ◽

10.1177/15593258211037127 ◽

2021 ◽

Vol 19 (3) ◽

pp. 155932582110371

Author(s):

Zhenzhen Wang ◽

Yuhan Hou ◽

Zhen Yao ◽

Yanyan Zhan ◽

Wenyue Chen ◽

...

Keyword(s):

Gastric Cancer ◽

Meta Analysis ◽

Interleukin 8 ◽

Cancer Prognosis ◽

Cochrane Library ◽

Comprehensive Search ◽

Funnel Plots ◽

The Relationship ◽

Significant Publication Bias ◽

Comprehensive Search Strategy

Background The relationship between interleukin-8 (IL-8) expression and the prognosis of gastric cancer (GC) patients has been reported, but the results are contradictory. Aim To investigate the effect of IL-8 expression on the prognosis of patients with GC. Method A comprehensive search strategy was used to search the PubMed, Web of Science and Cochrane Library databases. The total survival time was analysed using the RevMan 5.4 software. Through extensive search and meta-analysis of relevant studies, studies examining the relationship between IL-8 expression and prognosis in patients with GC were conducted to obtain more accurate estimates. Findings Eight studies (1843 patients) were included. The combined results of all the studies showed that high expression of IL-8 was a risk factor for poor prognosis in patients with GC (hazard ratio (HR): 2.08; 95% CI: 1.81–2.39). Sensitivity analysis suggested that the pooled HR was stable, and omitting a single study did not change the significance of the pooled HR. Funnel plots revealed no significant publication bias in the meta-analysis. Conclusion High IL-8 expression could be a negative prognostic biomarker for patients with GC.

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TGFB2 serves as a link between epithelial-mesenchymal transition and tumor mutation burden in gastric cancer

International Immunopharmacology ◽

10.1016/j.intimp.2020.106532 ◽

2020 ◽

Vol 84 ◽

pp. 106532 ◽

Cited By ~ 2

Author(s):

BoWen Yang ◽

Jin Bai ◽

Ruichuan Shi ◽

Xinye Shao ◽

Yujing Yang ◽

...

Keyword(s):

Gastric Cancer ◽

Epithelial Mesenchymal Transition ◽

Tumor Mutation Burden ◽

Mesenchymal Transition ◽

Mutation Burden

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Inflammation-based scores are associated with prognosis of patients with aneurysmal subarachnoid hemorrhage after neuro-intervention

Current Neurovascular Research ◽

10.2174/1567202617999201117120905 ◽

2020 ◽

Vol 17 ◽

Author(s):

Ho Jun Yi ◽

Dong Hoon Lee ◽

Jae Hoon Sung

Keyword(s):

Subarachnoid Hemorrhage ◽

Functional Outcome ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Prognostic Significance ◽

Density Lipoprotein ◽

Endovascular Intervention ◽

Roc Curve Analysis ◽

Lymphocyte To Monocyte Ratio ◽

Cutoff Values ◽

The Relationship

Objective: Prognostic significance of inflammatory response has been reported in various diseases. The objective of this study was to analyze the association between inflammation-based scores and prognosis of patients who underwent neuro-intervention for aneurysmal subarachnoid hemorrhage (SAH). Methods: Inflammation-based scores such as neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) were analyzed for aneurysmal SAH patients Results: A total of 498 patients were enrolled. Optimal cutoff values of inflammation-based scores of NLR, LMR, and MHR for unfavorable functional outcome were 5.7, 4.2, and 1.5, respectively (p < 0.001, < 0.001, and 0.004, respectively). In multivariate analysis, NLR value ≥ 5.7 (odds ratio [OR] 1.92, 95% CI 1.42–3.42; P = 0.008), LMR value < 4.2 (OR 1.74, 95% CI 1.48–2.98; P = 0.018), and MHR value ≥ 1.5 (OR 1.44, 95% CI 1.22–2.82; P = 0.040) were independently associated with unfavorable functional outcome. Conclusion: Inflammation based scores were associated with functional outcome after endovascular intervention for aneurysmal SAH. Higher NLR and MHR with lower LMR could predict unfavorable outcomes of aneurysmal SAH patients who underwent endovascular intervention. who underwent endovascular intervention. Unfavorable functional outcome was defined as modified Rankin Scale (mRS) score of 3-6. Receiver operating characteristic (ROC) curve analysis was performed to identify cutoff values of inflammation- based scores for predicting unfavorable functional outcome. Logistic regression analyses were performed to explore the relationship between inflammation-based scores and prognosis of patients.

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