Intratumoral gene expression profile of genes involved in 5-FU metabolism and angiogenesis, comparison with tumor invasion depth in patients with advanced gastric cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 56-56
Author(s):  
Mizutomo Azuma ◽  
Akira Naruke ◽  
Myungchul Kim ◽  
Kenji Ishido ◽  
Chikatoshi Katada ◽  
...  

56 Background: The biopsy specimen by endoscopy can only show the surface of its gene profiles. We hypothesis whether the biopsy specimen can reflect all part of gene profile or not. We tested how 5-FU related genes and angiogenesis gene expressed in the invasion depth in the primary tumor of the Stage II or III advanced gastric cancer. Methods: Twenty-five patients with stage II or III advanced gastric cancer who underwent gastrectomy were analyzed.Formalin-fixed, paraffin-embedded tumor tissues were dissected from the surface section (mainly mucosa), the middle section (mainly submucossa) and the deep section (the part invaded most deeply) of the primary tumor and the normal gastric mucosa tissue by the laser-captured microdissection technique and were analyzed for target gene expressions using a quantitative real-time polymerase chain reaction.We analyzed for target genes as TS, TP, DPD, ERCC1, EGFR, VEGF and HIF1α. Results: In the primary tumor, TP and HIF1α gene expression in the surface section was significantly higher than in the deep section (p=0.021, p=0.012). These gene expression and the depth of the primary tumor had a correlation coefficient (TP; r=0.29, HIF1α; r=0.33). There was no significantly difference between surface and deep section in the primary tumor in TS, DPD, ERCC1, VEGF, EGFR except TP and HIF1α. There was no significantly difference between surface and middle section in the primary tumor in all gene expression. There was no significantly difference between middle and deep section in the primary tumor in all gene expression. Conclusions: Only TP and HIF1α had tendency that these gene expression became higher as invaded from the surface section to the deep section of primary tumor. These data suggested that biopsy specimens could be predicted gene expression profile from the surface of gastric cancer. But as you know, gastric cancer has a heterogeneity gene profile. We need at least few samples to say whole gene expression of its tumors. This is preliminary data, it will need further study to proof these result.

2018 ◽  
Vol 29 ◽  
pp. viii219-viii220
Author(s):  
S.Y. Rha ◽  
G.Y. Ku ◽  
H.S. Kim ◽  
H.C. Chung ◽  
F.G. Amlashi ◽  
...  

2011 ◽  
Author(s):  
Han Sang Kim ◽  
Sang Cheol Kim ◽  
Chan Hee Park ◽  
Sang Joon Shin ◽  
Joong Bae Ahn ◽  
...  

2013 ◽  
Vol 1 (5) ◽  
pp. 825-827 ◽  
Author(s):  
KAZUHITO MIYACHI ◽  
YOUKI SAWADA ◽  
YOSUKE SHIDA ◽  
AKIRA SUGAWARA ◽  
HISASHI HISATOMI

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 72-72
Author(s):  
Masanori Terashima ◽  
Rie Makuuchi ◽  
Masanori Tokunaga ◽  
Yutaka Tanizawa ◽  
Etsuro Bando ◽  
...  

72 Background: Gastric cancer is well known as having heterogeneous features. Recently, the Asian Cancer Research Group (AGRG) had proposed a new classification scheme based on the gene expression profile of the tumor. However, the genomi/expression profiling of gastric cancer in Japanese patients is still unknown. We started a comprehensive molecular profiling study that analyzes genome and transcriptome of tumor obtained from cancer patients admitted to Shizuoka Cancer Center from 2014. We already had evaluated more than 1,500 samples from various type of cancer. Among them, 104 gastric cancer patients were analyzed. Methods: Fresh surgically resected tumor/normal samples and peripheral blood were obtained and whole-exome sequencing (Ion Proton, Life Technologies) and gene expression profiling (DNA microarray, Agilent Technologies) were performed. Patients were grouped based on the gene expression profile according to AGRG classification, and clinicopathological features were compared among the group. Results: Patients were classified into MSI in 14, MSS/EMT in 15, MSS/TP53+ in 38 and MSS/TP53- in 37, respectively. There was no significant difference of sex among the group. Age was significantly younger in MSS/EMT and MSS/TP53-. In MSI, tumor tended to be located at antrum, and differentiated type tumor was predominant. In MSS/EMT, advanced T stage (T4) and undifferentiated type of tumor was predominant. In MSS/TP53+, relatively less advanced stage and localized macroscopic type tumor was predominant. In MSS/TP53-, relatively advanced stage and invasive macroscopic type tumor was predominant. Although the follow-up period is insufficient, relapse-free survival was the worst in MSS/EMT and no patient recurred in MSI. Conclusions: Classification of gene expression profiling based on ACRG was possible in Japanese gastric cancer. Distribution and tumor characteristics were almost identical to ACRG cohort. Gene -expression profiling may be comprehensively used for tumor classification and further clinical trials of molecular targeting agents.


2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 3026-3026 ◽  
Author(s):  
Veena Shankaran ◽  
Kei Muro ◽  
Yung-Jue Bang ◽  
Ravit Geva ◽  
Daniel Virgil Thomas Catenacci ◽  
...  

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 48-48 ◽  
Author(s):  
Wei-Peng Yong ◽  
Sun Young Rha ◽  
Iain B. Tan ◽  
Su-Pin Choo ◽  
Nicholas Syn ◽  
...  

48 Background: Theoxaliplatin/S-1 (SOX) and cisplatin/S-1 (SP) regimens are interchangeably used in the management of advanced gastric cancer (AGC). We previously developed a classification tool using gene expression signatures which successfully stratified gastric cancer cell lines and primary tumour samples according to their sensitivity to SOX or SP ( Tan et al, Gastroenterology 2011). We now report the first prospective study to evaluate the feasibility and efficacy of using a genomic classifier to tailor treatment in this setting. Methods: Pts with histologically-confirmed locally-advanced, metastatic and recurrent GC were recruited from 3 centres in Singapore and South Korea. Tumours were analysed using the Affymetrix HG-U133 Plus 2.0 array and results were used to classify pts as G1 (oxaliplatin-sensitive), G2 (cisplatin-sensitive) and G3 (status unclear or gene expression not available). G1 and G2 pts were matched to SOX and SP regimens respectively, while G3 pts were assigned SOX. The primary endpoint was best overall response; secondary endpoints were turnaround time and biomarker analyses. Results: Between July 2, 2010, and Apr 2, 2015, we screened 85 AGC pts. 74 pts received at least 1 cycle of treatment and were evaluable for analysis. Median turnaround time was 7 working days (IQR, 5–9). The misclassification rate was 6%. After an initial 30 pts in the G1 subgroup were treated with SOX, subsequent pts ( N = 13) classified as G1 received the SP regimen. The ORR were 44.8%, 8.3%, 26.7% and 55.6% for G1 SOX, G1 SP, G2 SP ( N = 19), G3 SOX ( N = 12) respectively; and was higher in G1 pts treated with SOX compared with SP ( P = 0.033). Post hoc genomic reclassification based on Lei et al (Gastroenterology 2013) confirmed the utility of the metabolic subtype as a predictive marker of benefit from chemotherapy (log rank P value for PFS = 0.004). Conclusions: This bench-to-bedside effort establishes that molecular profiling to direct choice of conventional chemotherapy for AGC is possible within a reasonable timeframe. The clinical utility of our genomic classifiers in question are promising but warrant further investigation. Clinical trial information: NCT01100801.


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