Prognostic Significance of PD-1, PD-L1 and CD8 Gene Expression Levels in Gastric Cancer

Oncology ◽  
2020 ◽  
Vol 98 (7) ◽  
pp. 501-511
Author(s):  
Shuhei Ito ◽  
Takaaki Masuda ◽  
Miwa Noda ◽  
Qingjiang Hu ◽  
Dai Shimizu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Prognostic Significance ◽  
Expression Levels ◽  
Gene Expression Levels

scholarly journals A Sparse and Low-Rank Regression Model for Identifying the Relationships Between DNA Methylation and Gene Expression Levels in Gastric Cancer and the Prediction of Prognosis

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 854
Author(s):  
Yishu Wang ◽  
Lingyun Xu ◽  
Dongmei Ai
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Dna Methylation ◽  
Regression Model ◽  
The Cancer Genome Atlas ◽  
Low Rank ◽  
Expression Levels ◽  
Rank Regression ◽  
Prediction Of Prognosis ◽  
Gene Expression Levels

DNA methylation is an important regulator of gene expression that can influence tumor heterogeneity and shows weak and varying expression levels among different genes. Gastric cancer (GC) is a highly heterogeneous cancer of the digestive system with a high mortality rate worldwide. The heterogeneous subtypes of GC lead to different prognoses. In this study, we explored the relationships between DNA methylation and gene expression levels by introducing a sparse low-rank regression model based on a GC dataset with 375 tumor samples and 32 normal samples from The Cancer Genome Atlas database. Differences in the DNA methylation levels and sites were found to be associated with differences in the expressed genes related to GC development. Overall, 29 methylation-driven genes were found to be related to the GC subtypes, and in the prognostic model, we explored five prognoses related to the methylation sites. Finally, based on a low-rank matrix, seven subgroups were identified with different methylation statuses. These specific classifications based on DNA methylation levels may help to account for heterogeneity and aid in personalized treatments.

scholarly journals Association of high-evidence gastric cancer susceptibility loci and somatic gene expression levels with survival

2017 ◽  
Vol 38 (11) ◽  
pp. 1119-1128 ◽  
Author(s):  
Hyuna Sung ◽  
Nan Hu ◽  
Howard H Yang ◽  
Carol A Giffen ◽  
Bin Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Cancer Susceptibility ◽  
Susceptibility Loci ◽  
Expression Levels ◽  
Somatic Gene ◽  
Gene Expression Levels

scholarly journals Diagnostic and prognostic significance of glypican 5 and glypican 6 gene expression levels in gastric adenocarcinoma

2015 ◽  
Vol 3 (3) ◽  
pp. 584-590 ◽  
Author(s):  
MELIKE DINCCELIK-ASLAN ◽  
GUVEM GUMUS-AKAY ◽  
ATILLA HALIL ELHAN ◽  
EKREM UNAL ◽  
AJLAN TUKUN
Keyword(s):  
Gene Expression ◽  
Gastric Adenocarcinoma ◽  
Prognostic Significance ◽  
Expression Levels ◽  
Gene Expression Levels

Association of AREG exon 1 polymorphism with worse prognosis in Japanese and U.S. patients with gastric cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15022-e15022
Author(s):  
Takeru Wakatsuki ◽  
Wu Zhang ◽  
Dongyun Yang ◽  
Mizutomo Azuma ◽  
Yan Ning ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Predictive Marker ◽  
Expression Levels ◽  
Direct Dna Sequencing ◽  
Japanese Cohort ◽  
Egfr Ligands ◽  
The Us ◽  
Exon 1 ◽  
Gene Expression Levels

e15022 Background: Recent data suggest that Amphiregulin (AREG) and Epiregulin (EREG), ligand of EGFR pathway, is possibly a prognostic and predictive marker in gastrointestinal cancer. Previous data have shown that higher AREG and EREG gene expression levels are associated with better survival in metastatic colorectal cancer as well as gastric cancer (GC). Since polymorphisms in AREG and EREG may affect their gene expression levels or change their functions, we tested the hypothesis whether these polymorphisms could predict outcome in two ethnically and epidemiologically different GC cohorts from Japan and the US. Methods: One-hundred and sixty-nine Japanese (n=169), as a training set, and one-hundred and thirty-seven (n=137) the US patients, as a validation set, with histopathologically-confirmed localized (stage Ib to IV; AJCC-6th) GC were enrolled between 2002 and 2010. Four functional SNPs in AREG and five SNPs in EREG were selected. Genomic DNA was extracted from blood or tissue, and all samples were analyzed by PCR-based direct DNA-sequencing. Results: The median follow-up periods were 4.0 years in the Japanese cohort and 3.3 years in the US cohort, respectively. The median DFS and OS in the Japanese cohort were 4.8 and 5.8 years, whereas the median TTR and OS in the US cohort were 2.8 and 4.7 years, respectively. Only exon 1 polymorphism rs1615111 G/A was associated with outcome in Japanese cohort. Patients heterozygous G/A (n=23) showed a median OS of 2.7 years vs. 20.1 years for patients homozygous G/G (n=146) (HR: 1.83 [95%CI: 1.02-3.30], p=0.039). This result was successfully validated in the US cohort. Patients harboring at least one-A allele (n=14) showed a median OS of 2.8 years vs. 5.4 years for patients homozygous G/G (n=111) (HR: 2.54 [95%CI: 1.09-5.89], p=0.018). In the pooled multivariate analysis, these results were still conserved (HR=2.24 [95%CI: 1.36- 3.67], p=0.0015). Conclusions: AREG exon 1 polymorphism rs161511 may be negative prognostic factor in GC regardless ethnicity and regional differences in gastric cancer. Further clinical validation of SNPs in EGFR ligands are warranted.

Gene expression levels of HER2 and IL-8 and polymorphism in IL-8 associated with clinical outcome in advanced or metastatic gastric cancer treated with lapatinib in SWOG 0413 trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4647-4647 ◽  
Author(s):  
H. Chang ◽  
M. Azuma ◽  
B. Goldman ◽  
F. Nagashima ◽  
S. Iqbal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Clinical Outcome ◽  
Cyclin D1 ◽  
Kinase Inhibitor ◽  
Metastatic Gastric Cancer ◽  
Gene Expressions ◽  
Tissue Samples ◽  
Expression Levels ◽  
Gene Expression Levels

4647 Background: Lapatinib (GW572016) is a dual tyrosine kinase inhibitor of EGFR and HER2. In SWOG0413 trial, advanced or metastatic gastric cancer patients were treated with lapatinib. In this study, we investigated whether gene expressions and polymorphisms of EGF and angiogenesis pathway genes were associated with clinical outcome in the patients enrolled in SWOG0413 trial. Methods: A total of 46 patients were enrolled in SWOG0413 trial and treated with lapatinib. Blood and tissue samples were available from 42 and 37 patients, respectively. RT-PCR was performed for intratumoral gene expression levels of EGFR, HER2, VEGF, IL-8, COX2 and cyclin D1 genes. We also analyzed 8 polymorphisms in the EGF, EGFR, HER2, VEGF, IL-8, COX2 and cyclin D1 genes by PCR-RFLP. Results: Patients who have lower IL-8 [median overall survival (OS), 6 vs 3 months, p=0.03] and higher HER2 (6 vs 3 months, p=0.005) gene expression levels showed better OS. According to gene polymorphisms, patients who have A allele of IL-8 T251A polymorphism showed improved OS (A/A, 10 months vs T/A, 5 months vs T/T 3 months, p=0.04). And patients with A allele of IL-8 T251A and T allele of VEGF C936T polymorphisms showed better response rates (p<0.01, p<0.01, respectively). All other polymorphisms and gene expressions did not show significant association with clinical outcome. Conclusions: Our results suggest that intratumoral gene expression levels of HER2 and IL-8 and polymorphism in IL-8 are potential molecular predictors for survival in patients with advanced or metastatic gastric cancer treated with lapatinib. And polymorphisms in IL-8 and VEGF genes may be potential markers in predicting response in this population. A larger prospective study is needed to validate and confirm these preliminary findings. [Table: see text]

Gene Expression Levels of Cytokines in Peritoneal Washings from Patients with Gastric Cancer

Tumor Biology ◽  
2004 ◽  
Vol 25 (3) ◽  
pp. 117-121 ◽  
Author(s):  
Masahide Ikeguchi ◽  
Sachiko Matsumoto ◽  
Daiki Murakami ◽  
Shingo Kanaji ◽  
Shotaro Ohro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Expression Levels ◽  
Peritoneal Washings ◽  
Gene Expression Levels

scholarly journals High heterogeneity undermines generalization of differential expression results in RNA-Seq analysis

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Weitong Cui ◽  
Huaru Xue ◽  
Lei Wei ◽  
Jinghua Jin ◽  
Xuewen Tian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differential Expression ◽  
Small Sample ◽  
Differentially Expressed ◽  
Cancer Type ◽  
Rna Seq ◽  
Sample Sizes ◽  
Large Sample ◽  
Expression Levels ◽  
Gene Expression Levels

Abstract Background RNA sequencing (RNA-Seq) has been widely applied in oncology for monitoring transcriptome changes. However, the emerging problem that high variation of gene expression levels caused by tumor heterogeneity may affect the reproducibility of differential expression (DE) results has rarely been studied. Here, we investigated the reproducibility of DE results for any given number of biological replicates between 3 and 24 and explored why a great many differentially expressed genes (DEGs) were not reproducible. Results Our findings demonstrate that poor reproducibility of DE results exists not only for small sample sizes, but also for relatively large sample sizes. Quite a few of the DEGs detected are specific to the samples in use, rather than genuinely differentially expressed under different conditions. Poor reproducibility of DE results is mainly caused by high variation of gene expression levels for the same gene in different samples. Even though biological variation may account for much of the high variation of gene expression levels, the effect of outlier count data also needs to be treated seriously, as outlier data severely interfere with DE analysis. Conclusions High heterogeneity exists not only in tumor tissue samples of each cancer type studied, but also in normal samples. High heterogeneity leads to poor reproducibility of DEGs, undermining generalization of differential expression results. Therefore, it is necessary to use large sample sizes (at least 10 if possible) in RNA-Seq experimental designs to reduce the impact of biological variability and DE results should be interpreted cautiously unless soundly validated.

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