Optimizing the program of sequential chemotherapy for advanced gastric cancer based on gene-level CNVs called from ctDNA.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16068-e16068
Author(s):  
Wenqi Xi ◽  
Chenfei Zhou ◽  
Shouwei Zhang ◽  
Zhao Yi ◽  
Yawei Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Initial Treatment ◽  
Cellular Response ◽  
Heuristic Method ◽  
Functional Enrichment ◽  
Sequential Chemotherapy ◽  
Optimal Program ◽  
Blood Samples ◽  
Resistant Genes ◽  
Gene Level

e16068 Background: Tumor evolutionary trade-offs under treatment pressure can be utilized to optimize therapy. We aimed to profile the dynamic pattern of gene-level copy number variations (CNVs) for advance gastric cancer (GCA) patients who underwent sequential chemotherapy and optimized the therapy program. Methods: 27 chemo-naive advanced GCA patients with distant metastasis were enrolled. Peripheral blood samples were collected at different time points, including pre-therapy and disease progression on a specific regimen. Gene-level CNVs were called from ctDNA of blood samples and drug modified score (DMS) was defined as the ratio of CNV value between samples of pre- and post-treatment for each gene. Positive and negative DMS of a gene represented its resistance and sensitivity to a selected regimen, respectively. Then, the best initial regimen was selected and the optimal program of sequential chemotherapy was designed for each patient. Results: DMS of gene was calculated for four chemotherapy regimens, including platinum-based doublet regimen (Pt-2d), oral-fluorouracil prodrug (O-FP), paclitaxel-based regimen (PTX) and irinotecan-based regimen (CPT-11). Based on DMS distribution, resistant and sensitive genes were determined for each regimen through a heuristic method. Functional enrichment analysis showed that resistant genes mainly involved in cellular response to oxygen-containing compound and regulation of cell proliferation, while sensitive genes mainly involved in positive regulation of macromolecule biosynthetic process and regulation of apoptotic process. Then, drug resistant score (DRS, defined as DMS weighted sum of CNV values of resistant genes) was calculated and the regimen with the lowest DRS was selected as the best initial treatment for each patient. The best initial treatment of 16 patients was CPT-11, of 8 patients was O-FP, of 2 patients was Pt-2d and of 1 patient was PTX. Following that, the optimal program of sequential chemotherapy was designed according to the percentage of shared resistant genes between regimens for each patient, where two regimens with the lowest percentage were recommended to use one by one. Finally, prognostic analysis showed that differences between the optimal and practical program of sequential chemotherapy were negatively correlated to overall survival of patients. Conclusions: Based on gene-level CNVs called from ctDNA of blood samples, we determined the best initial treatment and designed the optimal program of sequential chemotherapy for advanced GCA patients, pacing a key step toward precision medicine in GCA field.

scholarly journals Screening Driving Transcription Factors in the Processing of Gastric Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Guangzhong Xu ◽  
Kai Li ◽  
Nengwei Zhang ◽  
Bin Zhu ◽  
Guosheng Feng
Keyword(s):  
Gastric Cancer ◽  
Transcription Factors ◽  
Regulatory Network ◽  
Target Genes ◽  
Transcriptional Regulatory Network ◽  
Expression Profiles ◽  
Functional Enrichment ◽  
Regulatory Mechanisms ◽  
Integrated Analysis ◽  
Transcriptional Regulatory

Background. Construction of the transcriptional regulatory network can provide additional clues on the regulatory mechanisms and therapeutic applications in gastric cancer.Methods. Gene expression profiles of gastric cancer were downloaded from GEO database for integrated analysis. All of DEGs were analyzed by GO enrichment and KEGG pathway enrichment. Transcription factors were further identified and then a global transcriptional regulatory network was constructed.Results. By integrated analysis of the six eligible datasets (340 cases and 43 controls), a bunch of 2327 DEGs were identified, including 2100 upregulated and 227 downregulated DEGs. Functional enrichment analysis of DEGs showed that digestion was a significantly enriched GO term for biological process. Moreover, there were two important enriched KEGG pathways: cell cycle and homologous recombination. Furthermore, a total of 70 differentially expressed TFs were identified and the transcriptional regulatory network was constructed, which consisted of 566 TF-target interactions. The top ten TFs regulating most downstream target genes were BRCA1, ARID3A, EHF, SOX10, ZNF263, FOXL1, FEV, GATA3, FOXC1, and FOXD1. Most of them were involved in the carcinogenesis of gastric cancer.Conclusion. The transcriptional regulatory network can help researchers to further clarify the underlying regulatory mechanisms of gastric cancer tumorigenesis.

scholarly journals Association between gene expression profiling of skin lesion and autoantibody in patients with systemic sclerosis

2020 ◽  
Author(s):  
Jun Inamo
Keyword(s):  
Gene Expression ◽  
Systemic Sclerosis ◽  
Skin Lesion ◽  
Topoisomerase I ◽  
Cellular Response ◽  
Rna Polymerase Iii ◽  
Functional Enrichment ◽  
Keratinocyte Differentiation ◽  
Study Cohort ◽  
Specific Autoantibody

AbstractObjectiveThe aim of this study was to investigate relevance between type of autoantibody and gene expression profile in skin lesion of systemic sclerosis (SSc), and identify specifically dysregulated pathways.MethodsSixty-one patients with SSc from the Genetics versus Environment in Scleroderma Outcome Study cohort and thirty-six healthy controls (HC) are included. Differentially expressed genes (DEGs) were extracted and functional enrichment and pathways analysis were conducted.ResultsCompared with HC, lists consisting of 2, 71, 10, 144 and 78 DEGs were created for patients without specific autoantibody, anti-centromere (ACA), anti-U1 RNP (RNP), anti-RNA polymerase III (RNAP) and anti-topoisomerase I (ATA) antibody, respectively. While part of enriched pathways overlapped, distinct pathways were identified except those without specific autoantibody: keratinocyte differentiation in ACA, NF-kB signaling and cellular response to transforming growth factor beta stimulus in RNAP, interferon alpha/beta signaling of RNP and cellular response to stress in ATA.ConclusionPathogenic pathways were identified according to type of autoantibodies by leveraging gene expression data of patients and controls from multi-center cohort. The current study will promote to explore new therapeutic target for SSc.Key messageDistinct pathways are associated with type of autoantibody in skin lesion of systemic sclerosis.

Immune Infiltration in Gastric Cancer Microenvironment and Its Clinical Significance

2020 ◽  
Author(s):  
An Zhi Zhang ◽  
Xin Yuan ◽  
Ya Li ◽  
Yu Fang Xie ◽  
Jiang Fen Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Immune Cells ◽  
Expression Profiles ◽  
Tnm Staging ◽  
Functional Enrichment ◽  
Cancer Tissue ◽  
Fuhrman Grade ◽  
Cytokine Activation ◽  
Immune Related Genes

Abstract Background In recent years, immunotherapy has developed rapidly and has gradually become one of the important methods for treatment of gastric cancer. The research on immune cells and immune-related genes in the tumor microenvironment greatly encourages the development of immunotherapy. Methods : The devolution algorithm (CIBERSORT) was applied to infer the proportion of 22 immune infiltrating cells based on gene expression profiles of gastric cancer tissue, which were downloaded from TCGA and GEO databases. The TCGA database was utilized to analyze the differential expression of immune-related genes, and explore the potential molecular functions of these genes.ResultsWe have observed the enrichment of multiple immune cells in the microenvironment of gastric cancer. Some of these cells are closely related to Fuhrman grade and TNM staging. Survival analysis showed that the infiltration level of CD8 + T cells, activated CD4 + memory T cells and M2 macrophages was significantly related to the prognosis of gastric cancer patients. The functional enrichment analysis of immune-related genes revealed that these genes were mainly associated with cytokine activation and response. Four significant modules were screened by PPI network and 20 key genes were screened from the modules, and the expression levels of CALCR and PTH1R are strikingly related to the prognosis of gastric cancer patients.ConclusionsThe type and number of infiltrating immune cells in the microenvironment of gastric cancer, as well as immune-related genes are closely related to tumor progression, and can be used as important indicators for patient prognosis assessment.

Enantioanalysis of tryptophan in whole blood samples using stochastic sensors—A screening test for gastric cancer

Chirality ◽  
2019 ◽  
Vol 32 (2) ◽  
pp. 215-222 ◽  
Author(s):  
Ruxandra‐Maria Ilie‐Mihai ◽  
Raluca‐Ioana Stefan‐van Staden ◽  
Lidia Magerusan ◽  
Maria Coros ◽  
Stela Pruneanu
Keyword(s):  
Gastric Cancer ◽  
Whole Blood ◽  
Screening Test ◽  
Blood Samples ◽  
Whole Blood Samples

scholarly journals Association of differentially expressed genes and autoantibody type in patients with systemic sclerosis

Rheumatology ◽  
2020 ◽  
Author(s):  
Jun Inamo
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Cellular Response ◽  
Rna Polymerase Iii ◽  
Skin Lesions ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Study Cohort ◽  
Healthy Controls ◽  
Specific Autoantibody

Abstract Objectives The aims of this study were to investigate the relationship between the type of autoantibody and gene expression profile in skin lesions from patients with SSc, and to identify specific dysregulated pathways in SSc patients compared with healthy controls. Methods Sixty-one patients with SSc from the Genetics vs Environment in Scleroderma Outcome Study cohort and 36 healthy controls were included in this study. Differentially expressed genes were extracted and functional enrichment and pathway analysis were conducted. Results Compared with healthy controls, lists containing 2, 71, 10, 144 and 78 differentially expressed genes were created for patients without specific autoantibody, ACA, anti-U1 RNP antibody (RNP), anti-RNA polymerase III antibody (RNAP) and anti-topoisomerase I antibody (ATA), respectively. While part of the enriched pathways overlapped, distinct pathways were identified except in those patients lacking specific autoantibody. The distinct enriched pathways included ‘keratinocyte differentiation’ for ACA, ‘nuclear factor κB signalling’ and ‘cellular response to TGF-β stimulus’ for RNAP, ‘interferon α/β signalling’ for RNP, and ‘cellular response to stress’ for ATA. Cell type signature score analysis revealed that macrophages/monocytes, endothelial cells and fibroblasts were associated with ACA, RNAP, ATA and the severity of the SSc skin lesions. Conclusion Pathogenic pathways were identified according to the type of autoantibody by leveraging gene expression data of patients and controls from a multicentre cohort. The current study may promote the search for new therapeutic targets for SSc.

scholarly journals MicroRNAs Regulated by the LPS/TLR2 Immune Axis as Bona Fide Biomarkers for Diagnosis of Acute Leptospirosis

mSphere ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Charles Solomon Akino Mercy ◽  
Natarajaseenivasan Suriya Muthukumaran ◽  
Prema Velusamy ◽  
Palanisamy Bothammal ◽  
Krishnamoorthi Sumaiya ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Early Diagnosis ◽  
Infectious Diseases ◽  
Cellular Response ◽  
Biological Activities ◽  
Mapk Signaling ◽  
Functional Enrichment ◽  
Clinical Samples ◽  
Systemic Complications

ABSTRACT Leptospirosis remains a significant human health issue due to its systemic complications. Therefore, biomarkers that are more effective are urgently needed for the early diagnosis of leptospirosis. MicroRNAs (miRNAs) are evolutionarily conserved regulatory RNAs that have shown the potential to be used as biomarkers for diagnosis, prognosis, and therapy of infectious diseases. In this study, we performed an unbiased screen using the miRNome miRNA array to identify circulating miRNAs with the potential to serve as authentic biomarkers for early diagnosis of leptospirosis. Because leptospiral lipopolysaccharide (LPS) is the predominant leptospiral antigen and plays a vital role in immunological and biological activities, we used LPS treated and untreated in vitro (THP1 cells) and in vivo (BALB/c mice) surrogate models to identify the LPS-specific miRNAs. Differential expression analysis revealed 18 miRNAs to be associated strongly with LPS stimulation in THP1 cells. Of these, three (miR-let-7b-5p, miR-144-3p, and miR-21-5p) were observed to be present at increased levels in vivo. The identified miRNAs were validated for their biomarker potential using serum samples from leptospirosis-negative patients and patients with confirmed cases of leptospirosis. Identified miRNAs were able to discriminate the acute leptospiral infection from other febrile diseases with a test sensitivity and specificity of 93.2% and 88.19%, respectively. Gene functional enrichment and protein-protein interaction (PPI) network analysis revealed that the identified miRNAs play important roles in disease signal transduction, signaling by interleukins, the stress-activated protein kinase signaling cascade, the mitogen-activated protein kinase (MAPK) signaling pathway, and the cellular response to a transforming growth factor β (TGF-β) stimulus with a notable interconnection between these biological processes. IMPORTANCE Here, we used miRNAs that are differentially regulated by the LPS/TLR2 immune axis to devise a miRNA-based diagnosis for leptospirosis. The study established the role of the circulating stable miRNAs (miR-21-5p, miR-144-3p, and miR-let-7b-5p) as an early diagnostic marker for leptospirosis. These miRNAs can be used to diagnose acute leptospirosis and also to differentiate leptospiral infection from other bacterial and spirochetal infections, as proved by the use of human clinical samples. Thus, our findings indicate that miRNAs can play a crucial role in the diagnosis of infectious diseases, like leptospirosis, that are generally misdiagnosed.

Sequential chemotherapy of S-1/weekly paclitaxel in patients with peritoneal metastasis of gastric cancer

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 4236-4236
Author(s):  
T. Yoshida ◽  
T. Osaragi ◽  
H. Murakami ◽  
T. Yoshikawa ◽  
A. Tsuburaya ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Peritoneal Metastasis ◽  
Weekly Paclitaxel ◽  
Sequential Chemotherapy

Registry of gastric cancer treatment evaluation (REGATE): Baseline characteristics of 10,299 patients from 22 countries

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4575-4575
Author(s):  
M. D. Ter-Ovanesov ◽  
Y. Bang ◽  
S. Yalcin ◽  
A. Roth ◽  
J. R. Zalcberg ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Initial Treatment ◽  
Treatment Plan ◽  
Tumor Location ◽  
Signet Ring Cell ◽  
Asia Pacific ◽  
Newly Diagnosed ◽  
Disease Registry ◽  
Target Sample Size ◽  
H Pylori

4575 Background: Gastric cancer (GC) is the second most common cause of cancer death in the world. Recent advances in diagnosis and treatment provide new options in the management of this poor-prognosis disease. REGATE is an international disease registry designed to assess real-world practice patterns for patients (pts) with GC. Methods: Pts with newly diagnosed GC were enrolled. The target sample size was calculated according to the GC prevalence in participating countries. Data were collected at 2 visits occurring within a 10-month timeframe: baseline (pts and tumor characteristics, treatment plan) and after completion of initial treatment (actual therapy received). Characteristics of the patients at the time of enrollment are described. Results: From August 2004 to July 2008, 10,299 pts were enrolled by 223 investigators in 22 countries (Asia-Pacific 43%, Europe 31%, Latin-America 20%, and North Africa 6%). Characteristics are as follows. Median age 60 years (range: 18–104) with 23% of pts <50 years. Male 65%, female 35%; 91% of pts were symptomatic; 8% had family history of GC; and 32% had H. pylori infection. GC was diagnosed by endoscopy in 95% of pts. Primary tumor location: antrum 39%, body 39%, proximal 17%. Histopathological type was assessed using WHO, Lauren, and/or Ming classifications in 75%, 60% and 31% of pts, respectively. The most common histopathological sub-types were diffuse (51%) and intestinal (44%) according to Lauren; signet ring cell (41%) and tubular (22%) according to WHO. Most patients (55%) had a poorly/undifferentiated tumor. AJCC stage at diagnosis: I-21%, II-20%, III-21%, IV-38%. Initial choice of planned therapy was mainly based on stage (69% of pts) and determined by either a multidisciplinary team (41%) or a surgeon alone (37%). Conclusions: REGATE is the largest prospective international disease registry that provides new insight into the characteristics of patients with newly diagnosed GC. Results including worldwide treatment patterns over time are expected after all patients have completed their initial treatment. [Table: see text]

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