Evaluation of prognostic factors in gene expression and clinicopathologic characteristics in patients with adjuvant chemotherapy for advanced gastric cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 61-61
Author(s):  
M. Azuma ◽  
K. Ishido ◽  
A. Takeuchi ◽  
A. Naruke ◽  
K. Higuchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Prognostic Factor ◽  
Intestinal Type ◽  
Diffuse Type ◽  
Gene Expressions ◽  
Group Iii ◽  
Type Group ◽  
Group I

61 Background: We reported TS expression is an independent prognostic factor in patients with gastric cancer who received postoperative adjuvant chemotherapy with S-1 at 2010 ASCO GI (abstract 32). These pharmacogenomic finding will help for choosing chemotherapeutic agents for personalized therapy in the future. Our aim was to indicate association of TS expression with clinicopathological characteristics in the same patient population. Methods: 39 patients with stage II or III advanced gastric cancer who underwent gastrectomy were analyzed. These patients received adjuvant chemotherapy with S-1 after surgery. Formalin-fixed, paraffin-embedded tumor tissues were dissected by the laser-captured microdissection technique and analyzed for target gene expressions using a quantitative real-time PCR. Results: There were no significant differences between stage II and III in TS gene expressions. TS expression (low ≤ 0.72, high > 0.72) and histological type (intestinal and diffuse) are evaluated for PFS and OS. Patients were classified as Group I (n = 5); low TS and intestinal type, Group II (n = 14); low TS and diffuse type, Group III (n = 13); high TS and diffuse type and Group IV (n = 7); high TS and intestinal type. There were significant differences between these four groups (Kaplan-Meier survival analysis, log-rank test, PFS: p = 0.0112 OS: p = 0.0128). The survival curve showed longer survival both PFS and OS in Groups 1 > 2 > 3 > 4. In low TS situation (responders as Group I and II), there is a trend in patients with intestinal type had a longer survival compared to diffuse type (Group I > II). In high TS situation (non-responders as Group III and IV), the result are opposite, there is a trend in patients with diffuse type had a longer survival compared to Intestinal type (Group III > IV). Conclusions: These data suggest that TS gene expression levels may be molecular markers of prognostic factor for patients with adjuvant chemotherapy for resectable gastric cancer. S-1 might be effect different behavior by both histological type and TS expression. Prospective studies are needed to validate these preliminary findings. No significant financial relationships to disclose.

scholarly journals Cardia Gastric Cancer Is Associated With Increased PIK3CA Amplifications and HER2 Expression Than Noncardia Gastric Cancer According to Lauren Classification

2021 ◽  
Vol 11 ◽  
Author(s):  
Shih-Min Pai ◽  
Kuo-Hung Huang ◽  
Ming-Huang Chen ◽  
Wen-Liang Fang ◽  
Yee Chao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Factor ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Genetic Alterations ◽  
Clinicopathological Features ◽  
Independent Prognostic Factor ◽  
Intestinal Type ◽  
Diffuse Type ◽  
Recurrence Patterns

BackgroundTo date, few reports have investigated genetic alterations and clinicopathological features in cardia and noncardia gastric cancer (GC).MethodsIn total, 435 GC patients receiving curative surgery were included. The clinicopathological features, recurrence patterns, prognoses and genetic alterations were compared between cardia and noncardia GC patients.ResultsAmong the 435 enrolled patients, 47 (10.8%) had cardia GC. Compared with noncardia GC, cardia GC was associated with more intestinal-type tumors and similar initial recurrence patterns and 5-year overall survival (OS; 50.8% vs. 50.5%, P = 0.480) and disease-free survival (DFS; 48.6% vs. 48.9%, P = 0.392) rates. For both intestinal-type GC and diffuse-type GC, the clinicopathological features and 5-year OS and DFS rates were not significantly different between the cardia and noncardia GC patients. Multivariable analysis showed that cardia GC was not an independent prognostic factor. Compared with noncardia GC, cardia GC was associated with increased PIK3CA amplification than in patients with intestinal-type GC and was associated with increased HER2 expression in patients with diffuse-type GC.ConclusionsCardia GC is not an independent prognostic factor. In cardia GC patients with intestinal-type GC, PIK3CA amplification was more common, and in those with diffuse-type GC, HER2 expression was more common. Targeted therapy may be beneficial for these patient subgroups.

Impact of dihydrofolate reductase (DHFR) and thymidylate synthase (TS) on outcomes of postoperative patients with gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4053-4053
Author(s):  
J. Matsubara ◽  
Y. Yamada ◽  
T. Shimoda ◽  
T. Eguchi ◽  
T. Hamaguchi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Intestinal Type ◽  
Cancer Center ◽  
Diffuse Type ◽  
First Line ◽  
Gene Expressions ◽  
Primary Tumors ◽  
First Line Therapy ◽  
Center Hospital ◽  
Poor Outcomes

4053 Background: The clinical significance of biomarkers in resected gastric cancer (GC) remains unclear. Detailed exploratory evaluations are required to better understand the clinical implications of biomarkers. Methods: The study group comprised 87 patients who received chemotherapy for recurrent or residual GC after resection of their primary tumors at National Cancer Center Hospital. The patients received 1 to 5 regimens of chemotherapy (median: 2). Total RNA was isolated from laser-captured tumor cells of the resected cancer specimens, and the gene expressions of TS, DPD, DHFR, ERCC1, MRP1, and 22 other biomarkers related to anticancer drug sensitivity were quantitatively evaluated by a real-time RT-PCR assay. Results: The gene expressions of TS, DHFR, MTHFD, RRM1, and ERCC1 were significantly related to survival ( Table ). Multivariate analysis revealed that high DHFR (p < 0.001, RR = 1.70 [95% CI, 1.28–2.29]) and high TS (p = 0.004, RR = 1.53 [1.15–2.06]) gene expressions were independently related to poor survival. As compared with intestinal type tumors, diffuse type tumors had higher DPD (p < 0.001) and lower Her2 (p < 0.001) gene expressions. As for first line chemotherapy, an analysis of 29 patients treated with S-1, an oral DPD inhibitory fluoropyrimidine, showed that patients with diffuse type tumors tended to respond better (p = 0.13) than those with intestinal type tumors. An analysis of 29 patients treated with cisplatin plus irinotecan as first line therapy showed that low ERCC1 gene expression was slightly but not significantly related to a better response (p = 0.087). Analyses of patients treated with other first line regimens revealed no significant correlation of any biomarker with response. Conclusions: Increased gene expressions of DHFR and TS in surgical specimens are significantly predictors of poor outcomes in postoperative patients with GC. [Table: see text] [Table: see text]

scholarly journals Analysis of gastric cancer transcriptome allows the identification of histotype specific molecular signatures with prognostic potential

2021 ◽  
Author(s):  
Adriana Carino ◽  
Luigina Graziosi ◽  
Silvia Marchianò ◽  
Michele Biagioli ◽  
Elisabetta Marino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Intestinal Type ◽  
Diffuse Type ◽  
Rna Seq ◽  
Gastric Cancers ◽  
The Third ◽  
Common Malignancy

AbstractGastric cancer is the fifth most common malignancy but the third leading cause of cancer-associated mortality worldwide. Therapy for gastric cancer remain largely suboptimal making the identification of novel therapeutic targets an urgent medical need. In the present study we have carried out a high-throughput sequencing of transcriptome expression in patients with gastric cancers. Twenty-four patients, among a series of 53, who underwent an attempt of curative surgery for gastric cancers in a single center, were enrolled. Patients were sub-grouped according to their histopathology into diffuse and intestinal types, and the transcriptome of the two subgroups assessed by RNAseq analysis and compared to the normal gastric mucosa. The results of this investigation demonstrated that the two histopathology phenotypes express two different patterns of gene expression. A total of 2064 transcripts were differentially expressed between neoplastic and non neoplastic tissues: 772 were specific for the intestinal type and 407 for the diffuse type. Only 885 transcripts were simultaneously differentially expressed by both tumors. The per pathway analysis demonstrated an enrichment of extracellular matrix and immune dysfunction in the intestinal type including CXCR2, CXCR1, FPR2, CARD14, EFNA2, AQ9, TRIP13, KLK11 and GHRL. At the univariate analysis reduced levels AQP9 was found to be a negative predictor of 4 years survival. In the diffuse type low levels CXCR2 and high levels of CARD14 mRNA were negative predictors of 4 years survival. In summary, we have identified a group of genes differentially regulated in the intestinal and diffuse histo-types of gastric cancers with AQP9, CARD14 and CXCR2 impacting on patients prognosis, although CXCR2 is the only factor independently impacting overall survival.Simple summaryGastric cancer is the fifth most common malignancy and the third leading cause of cancer-associated mortality worldwide. Although several new pharmacological approaches are currently developed, surgery remains the unique valid option of treatment but survival remains very poor over the last decades. Therefore, understanding the underlying molecular mechanisms of the gastric carcinogenesis and identifying sensitive biomarkers could be helpful for the prevention and treatment of the disease. Currently, the high-throughput sequencing techniques, in particular the transcriptomic analysis (RNA-seq) represents a validated technique to obtain a molecular characterization of human cancers. Moreover, it has been established that genetic susceptibility and environmental factors, such as microbial infections may contribute to carcinogenesis. We have characterized the different patterns of gene expression, using RNA-seq analysis and correlated these findings with gastric cancer histological subtypes.

scholarly journals Clinical Significance of coexisting histological diffuse type in stage II/III gastric cancer: A retrospective study

2020 ◽  
Author(s):  
Hiroaki Tanaka ◽  
Mami Yoshii ◽  
Yuichiro Miki ◽  
Tatsuro Tamura ◽  
Takahiro Toyokawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Signet Ring Cell Carcinoma ◽  
Signet Ring Cell ◽  
Stage Ii ◽  
Intestinal Type ◽  
Stage Iii ◽  
Diffuse Type ◽  
Signet Ring ◽  
Ring Cell

Abstract Background: Since 1965, the Laurén classification has been used most commonly for gastric adenocarcinoma, with two types, intestinal type and diffuse type. Signet ring cell carcinoma (Sig) and non-solid poorly differentiated adenocarcinoma (Por2) are the histological forms of diffuse type and are often found in advanced tumors, and they seem to be associated with a poor prognosis. S-1 based adjuvant chemotherapy for patients with stage II/III gastric cancer has generally been accepted in Japan, but histological type does not alter treatment strategy. The aim of the present study was to investigate the prognostic impact of the histopathologic mixture of Sig and Por2 in patients with stage II/III gastric cancer treated with S-1 adjuvant chemotherapy.Methods: The clinicopathological data of 968 gastric carcinoma patients who underwent gastrectomy between 2007 and 2016 at our department were retrospectively analyzed. In this study, tumors containing Sig or Por2 were classified as Diffuse type, and those not containing them were classified as Intestinal type.Results: There were 307 cases of Diffuse type and 661 of Intestinal type. Diffuse type included 189 cases with Sig. Pathological diagnosis of Sig was an independent risk factor for peritoneal recurrence in patients with stage II/III. Patients with Diffuse type had worse overall survival than those with Intestinal type in Stage III. Of the patients who received S-1 adjuvant chemotherapy, the prognosis of Stage III patients with Sig but not Por2 was Significantly worse compared to patients with Intestinal type.Conclusions: The coexistence of Signet ring cell carcinoma in the primary tumor was associated with a poor prognosis in patients with stage III gastric cancer. These findings suggest that, because mixed Sig gastric cancer had a high risk of peritoneal recurrence even if adjuvant chemotherapy were performed, the pathological diagnosis should be considered when determining the therapeutic strategy for adjuvant chemotherapy in stage III gastric cancer.

HEALING THROUGH CYTOKINE REGULATION IN DNBS INDUCED INFLAMMATORY BOWEL DISEASE IN RATS BY HOLARRHENA ANTIDYSENTERICA

INDIAN DRUGS ◽  
2016 ◽  
Vol 53 (08) ◽  
pp. 57-64
Author(s):  
S. Johari ◽  
◽  
C. Joshi ◽  
T. Gandhi
Keyword(s):  
Gene Expression ◽  
Inflammatory Bowel Disease ◽  
Body Weight ◽  
Bowel Disease ◽  
Stool Consistency ◽  
Cytokine Gene ◽  
Group Iii ◽  
Group I ◽  
Holarrhena Antidysenterica ◽  
Inflammatory Bowel

The objective of the study was to ascertain antioxidant, anti-inflammatory and cytokine gene regulation activity of Holarrhena antidysenterica (HA) in dinitrobenzene sulfonic acid (DNBS) induced inflammatory bowel disease (IBD) in rats. Sprague Dawley rats were divided into 6 groups, Group I (normal), Group II (50% ethanol intracolonically on 11th day), Group III (Model). Group IV to VI were given standard drug 5-amino salicylic acid (5-ASA) (100mg/kg) and hydromethanolic extract of Holarrhena antidysenterica (MEHA) 450 mg/kg and MEHA 600 mg/kg respectively for 18 days once p.o. Colitis was induced with DNBS (180mg/kg in 50% ethanol) intracolonically in animals of Group III-VI on 11th day. Body weight, food & water intake and stool consistency of each group was noted. On 18th day, blood was collected for cortisol estimation. Colon length and weight was measured. Cytokine gene expression studies of colon in group I, II, III, IV and VI was done using Real Time RT-PCR. Colon histopathology, Disease Activity Index (DAI) and Colon Mucosal Disease index (CMDI) parameters were studied. Nitric oxide (NO), malondialdehyde (MDA), myeloperoxidase (MPO) and superoxide dismutase (SOD) were estimated in colon homogenate. DNBS model control showed significant reduction in body weight, water and food intake, SOD, colon length and significant increase in stool consistency, colon weight, MDA, MPO, NO, CMDI, DAI, cortisol, IL-4, IL-6, IL-12 and IFN-gamma cytokines gene expression. Pretreatment with 5-ASA (100mg/kg) and MEHA (450 and 600 mg/kg) significantly reversed the above. MEHA reduced severity of IBD induced by DNBS through its anti-inflammatory, antioxidant and gene modulatory activity.

scholarly journals Molecular Network Profiling in Intestinal- and Diffuse-Type Gastric Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3833
Author(s):  
Shihori Tanabe ◽  
Sabina Quader ◽  
Ryuichi Ono ◽  
Horacio Cabral ◽  
Kazuhiko Aoyagi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Drug Resistance ◽  
Signaling Pathways ◽  
Pathway Analysis ◽  
Rna Binding ◽  
Binding Protein ◽  
Diffuse Type ◽  
Mesenchymal Transition ◽  
Diffuse Type Gastric Cancer

Epithelial-mesenchymal transition (EMT) plays an important role in the acquisition of cancer stem cell (CSC) feature and drug resistance, which are the main hallmarks of cancer malignancy. Although previous findings have shown that several signaling pathways are activated in cancer progression, the precise mechanism of signaling pathways in EMT and CSCs are not fully understood. In this study, we focused on the intestinal and diffuse-type gastric cancer (GC) and analyzed the gene expression of public RNAseq data to understand the molecular pathway regulation in different subtypes of gastric cancer. Network pathway analysis was performed by Ingenuity Pathway Analysis (IPA). A total of 2815 probe set IDs were significantly different between intestinal- and diffuse-type GC data in cBioPortal Cancer Genomics. Our analysis uncovered 10 genes including male-specific lethal 3 homolog (Drosophila) pseudogene 1 (MSL3P1), CDC28 protein kinase regulatory subunit 1B (CKS1B), DEAD-box helicase 27 (DDX27), golgi to ER traffic protein 4 (GET4), chromosome segregation 1 like (CSE1L), translocase of outer mitochondrial membrane 34 (TOMM34), YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), ribonucleic acid export 1 (RAE1), par-6 family cell polarity regulator beta (PARD6B), and MRG domain binding protein (MRGBP), which have differences in gene expression between intestinal- and diffuse-type GC. A total of 463 direct relationships with three molecules (MYC, NTRK1, UBE2M) were found in the biomarker-filtered network generated by network pathway analysis. The networks and features in intestinal- and diffuse-type GC have been investigated and profiled in bioinformatics. Our results revealed the signaling pathway networks in intestinal- and diffuse-type GC, bringing new light for the elucidation of drug resistance mechanisms in CSCs.

The relationship between HER-2 and TOPO-2A gene expression and clinicopathologic results in gastric cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14670-e14670
Author(s):  
Metin Ozkan ◽  
Esra Ermis Turak ◽  
Halit Karaca ◽  
Mevlude Inanc ◽  
Veli Berk ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Median Overall Survival ◽  
Intestinal Type ◽  
Negative Group ◽  
Diffuse Type ◽  
Her 2 ◽  
Gastric Cancer Patients

e14670 Background: HER-2 and Topo-2A genes are settled on a chromosome 17 and their co-amplification rates are high. In this study, early gastric cancer patients who received adjuvant chemo-radiotherapy and chemotherapy were evaluated with HER-2 and Topo-2A expression in association with clinical and histopathologic findings. Methods: A total of 103 gastric cancer patients were included the study. The HER-2 and Topo-2A levels were measured by immunohistochemistry in postoperative tumor materials. A standard evaluation method was admitted for HER-2 positivity, while Topo-2A nuclear staining 3+ and 4+ were considered as overexpression. Those with level 2+ or 3+ of HER-2, the FISH test were attempted. Results: The median follow-up was 19 months (ranges 2–70 months). Forty-six patients (44%) relapsed during follow-up whereas 60 patients (58%) had died. The median overall survival (mOS) was 23 months. Histopathologies of HER-2 positive patients were intestinal type in 7 (87.5%) and diffuse type in one (12.5%) patient. In the follow-up period 4 patients (50%) were died (mOS was 17 months in this group). Median overall survival was 23 months in HER-2 negative group (p=0.6). Histopathologies of Topo-2A positive patients were intestinal type in 9 (64.2%) and diffuse type in 5 (35.8%) patient. In the follow-up period 8 patients (57%) were died (mOS was 22 months in this group). Median overall survival was 23 months in Topo-2A negative group (p=0.8). Three patients (37.5%) who had HER-2 positive histopathologies also had Topo-2A positivity. Conclusions: Overexpression rates of HER-2 in gastric cancer were reported 6.8-34%. Racial differences and different scoring techniques thought to be impact the results. Co-amplification rate of HER-2 and Topo-2A was reported 34% in gastric cancer. In our study HER-2 and Topo-2A overexpression rates were 7.7% and 13.6% respectively and co-amplification of HER-2 with Topo-2A rate was 37.5% is also similar to the other studies. Stages of patients with HER-2 and Topo-2A overexpression were similar to the distribution of the overall patients. While intestinal subtypes showed a higher rate of HER-2 overexpression, the median survival times tend to be shorter in HER-2 positive patients.

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