Tumor Size as a Prognostic Factor in Gastric Cancer Patient

Im, Won Jin,Kim, Min Gyu,Ha, Tae Kyung,Kwon, Sung Joon The Korean Gastric Cancer Association 2012 Journal of gastric cancer Vol.12 No.3

Purpose: The purpose of this study is to investigate the prognostic significance of tumor size for 5-year survival rate in patients with gastric cancer. Materials and Methods: A total of 1,697 patients with gastric cancer, who underwent potentially curative gastrectomy, were evaluated. Patients were divided into 4 groups as follows, according to the median size of early and advanced gastric cancer, respectively: small early gastric cancer (tumor size ${\leq}3$ cm), large early gastric cancer (tumor size >3 cm), small advanced gastric cancer (tumor size ${\leq}$ 6 cm), and large advanced gastric cancer (tumor size >6 cm). The prognostic value of tumor size for 5-year survival rate was investigated. Results: In a univariate analysis, tumor size is a significant prognostic factor in advanced gastric cancer, but not in early gastric cancer. Multivariate analysis showed that tumor size is an independent prognostic factor for 5-year survival rate in advanced gastric cancer (P=0.003, hazard ratio=1.372, 95% confidence interval=1.115~1.690). When advanced gastric cancer is subdivided into 2 groups, according to serosa invasion: Group 1; serosa negative (T2 and T3, 7th AJCC), and Group 2; serosa positive (T4a and T4b, 7th AJCC), tumor size is an independent prognostic factor in Group 1 (P=0.011, hazard ratio=1.810, 95% confidence interval=1.149~2.852) and in Group 2 (P=0.033, hazard ratio=1.288, 95% confidence interval=1.020~1.627), respectively. Conclusions: Tumor size is an independent prognostic factor in advanced gastric cancer irrespective of the serosa invasion, but not in early gastric cancer.

A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets

Deng, Niantao,Goh, Liang Kee,Wang, Hannah,Das, Kakoli,Tao, Jiong,Tan, Iain Beehuat,Zhang, Shenli,Lee, Minghui,Wu, Jeanie,Lim, Kiat Hon,Lei, Zhengdeng,Goh, Glenn,Lim, Qing-Yan,Tan, Angie Lay-Keng,Sin P BMJ Group 2012 Gut Vol.61 No.5

<P><B>Objective</B></P><P>Gastric cancer is a major gastrointestinal malignancy for which targeted therapies are emerging as treatment options. This study sought to identify the most prevalent molecular targets in gastric cancer and to elucidate systematic patterns of exclusivity and co-occurrence among these targets, through comprehensive genomic analysis of a large panel of gastric cancers.</P><P><B>Design</B></P><P>Using high-resolution single nucleotide polymorphism arrays, copy number alterations were profiled in a panel of 233 gastric cancers (193 primary tumours, 40 cell lines) and 98 primary matched gastric non-malignant samples. For selected alterations, their impact on gene expression and clinical outcome were evaluated.</P><P><B>Results</B></P><P>22 recurrent focal alterations (13 amplifications and nine deletions) were identified. These included both known targets (<I>FGFR2</I>, <I>ERBB2</I>) and also novel genes in gastric cancer (<I>KLF5</I>, <I>GATA6</I>). Receptor tyrosine kinase (RTK)/RAS alterations were found to be frequent in gastric cancer. This study also demonstrates, for the first time, that these alterations occur in a mutually exclusive fashion, with <I>KRAS</I> gene amplifications highlighting a clinically relevant but previously underappreciated gastric cancer subgroup. <I>FGFR2</I>-amplified gastric cancers were also shown to be sensitive to dovitinib, an orally bioavailable FGFR/VEGFR targeting agent, potentially representing a subtype-specific therapy for <I>FGFR2</I>-amplified gastric cancers.</P><P><B>Conclusion</B></P><P>The study demonstrates the existence of five distinct gastric cancer patient subgroups, defined by the signature genomic alterations <I>FGFR2</I> (9% of tumours), <I>KRAS</I> (9%), <I>EGFR</I> (8%), <I>ERBB2</I> (7%) and <I>MET</I> (4%). Collectively, these subgroups suggest that at least 37% of gastric cancer patients may be potentially treatable by RTK/RAS directed therapies.</P>

Hypermethylation and Clinicopathological Significance of RASAL1 Gene in Gastric Cancer

Chen, Hong,Pan, Ying,Cheng, Zheng-Yuan,Wang, Zhi,Liu, Yang,Zhao, Zhu-Jiang,Fan, Hong Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Background: Recent studies have suggested that expression of the RAS protein activator like-1 gene (RASAL1) is decreased in gastric carcinoma tissues and cell lines, indicated a role in tumorigenesis and development of gastric cancer. Reduced expression of RASAL1 could result in aberrant increase of activity of RAS signaling pathways in cancer cells. However, the exact mechanism which induces down-regulation of the RASAL1 gene remains unclear. This study aimed to determine the methylation status and regulation of RASAL1 in gastric cancer. Materials and Methods: Using the methylation-specific polymerase chain reaction (MSP), the methylation status of CpG islands in the RASAL1 promoter in gastric cancers and paired adjacent non-cancerous tissues from 40 patients was assessed and its clinicopathological significance was analyzed. The methylation status of RASAL1 in gastric cancer lines MKN-28, SGC-790l, BGC-823, as well as in normal gastric epithelial cell line GES-l was also determined after treatment with a DNA methyltransferase inhibitor, 5-aza-2'-doexycytidine (5-Aza-CdR). RAS activity (GAS-GTP) was assessed through a pull-down method, while protein levels of ERK1/2, a downstream molecule of RAS signaling pathways, were determined by Western blotting. Results: The frequencies of RASAL1 promoter methylation in gastric cancer and paired adjacent non-cancerous tissues were 70% (28/40) and 30% (12/40) respectively (P<0.05). There were significantly correlations between RASAL1 promoter methylation with tumor differentiation, tumor size, invasive depth and lymph node metastasis in patients with gastric cancer (all P<0.05), but no correlation was found for age or gender. Promoter hypermethylation of the RASAL1 gene was detected in MKN-28, SGC-790l and BGC-823 cancer cells, but not in the normal gastric epithelial cell line GES-1. Elevated expression of the RASAL1 protein, a decreased RAS-GTP and p-ERK1/2 protein were detected in three gastric cancer cell lines after treatment with 5-Aza-CdR. Conclusions: Aberrant hypermethylation of the RASAL1 gene promoter frequently occurs in gastric cancer tissues and cells. In addition, the demethylating agent 5-Aza-CdR can reverse the hypermethylation of RASAL1 gene and up-regulate the expression of RASAL1 significantly in gastric cancer cells in vivo. Our study suggests that RASAL1 promoter methylation may have a certain relationship with the reduced RASAL1 expression in gastric cancer.

Helicobacter pylori와 위암

홍원선 대한암예방학회 2003 Journal of cancer prevention Vol.8 No.4

Borrmann 4형으로 진단된 진행성 위암환자의 임상적 검토

천영국,김영태,홍수진,김진오,조주영,이문성,심찬섭 순천향의학연구소 2001 Journal of Soonchunhyang Medical Science Vol.7 No.1

Background/Aim: It is difficult to dignosis of Borrmann type 4 gastric cancer at the early stage, because of its special morphology. Most of the cases have been detected at the advanced stage with poor survival rate. We reviewed patients with advanced gastric cancer, to define clinicopathologic characteristics of Borrmann type 4 gastric cancer comparing other types of gastric cancer. Methods: 1033 patients with advanced gastric cancer were divided into two groups, consisting of 50 patients with Borrmann type 4 gastric cancer, and the remaining 983 patients with all other types of gastric cancer, which were then compared clinicopatologically. Results: The proportion of Borrmann type 4 gastric cancer to advanced gastric cancer was 4.48%(50/1,033). The patients with Borrmann type 4 gastric cancer to advanced gastric cancer was 4.48%(50/1,033). The patients with Borrmann type 4 gastric cancer were composed 20 males and 30 males and revealed the highest frequency 3rd decade (24.0%) in age (range 26-78). In giant folds group (n=27), the number of poorly differentiated cell type, lymph node metastasis, peritoneal seeding were 20 (74.1%), 17 (63,0%), 12 (44.4%). In non-giant folds group (n=23), the number of poorly differentiated type, lymph node metastasis, peritoneal seeding were 17 (73.9%), 15 (65.2%), 6 (26.1%). Rate of tumor invasion in serosa and beyound serosa was 88.9% in giant fold group, 63.0% in non-giant fold group. Surgery was performed in only 32% as a modality of treatment (vs. 82.5%). Characteristics findings of Borrmann type 4 gastric cancer in EUS showed a thickening of the third (submucosa) and fourth (muscularis propria) layers in 72% of 50 patients, and a well preserved five-layered gastric wall structure in 33 patients. Conclusions: We concluded that Borrmann type 4 gastric cancer was diagnosed more in females, as a more advanced disease, early detection was needed. And endoscopic ultrasonography is useful for diagnosis of Borrmann type 4 gastric cancer in the cases of suspicious results of gastroscopy.

Combined Detection of Serum MiR-221-3p and MiR-122-5p Expression in Diagnosis and Prognosis of Gastric Cancer

Zhang, Yan,Huang, Huifeng,Zhang, Yun,Liao, Nansheng The Korean Gastric Cancer Association 2019 Journal of gastric cancer Vol.19 No.3

Purpose: To investigate the clinical value of serum miR-221-3p and miR-122-5p expression levels in the diagnosis and prognosis of gastric cancer. Materials and Methods: Serum samples from 141 gastric cancer cases (gastric cancer group), 110 gastric polyps (gastric polyp group), and 75 healthy people (healthy control) were used to detect miR-221-3p and miR-122-5p expression using real-time reverse transcription polymerase chain reaction. Results: Serum miR-221-3p expression was significantly higher in the gastric cancer group than in the gastric polyp group, and it was significantly lower than that before operation. The miR-221-3p expression was significantly higher in the death group than in the survival group. The proliferation and migration ability significantly increased and the apoptosis rate significantly decreased by miR-221-3p transfection in gastric cancer cells. In contrast, the function of miR-122-5p in gastric cancer cells was opposite of miR-221-3p. Serum miR-221-3p expression was negatively correlated with that of miR-122-5p in gastric cancer. Serum miR-221-3p and miR-122-5p expressions were significantly correlated with the degree of differentiation, tumor, node, metastasis stage, lymph node metastasis, and invasion depth. miR-221-3p and miR-122-5p expression levels were independent prognostic factors for postoperative gastric cancer. In the diagnosis and predicting prognosis of gastric cancer, receiver operating characteristic analysis revealed that the area under curve of combined detection of serum miR-221-3p and miR-122-5p expression had a greater diagnostic effect than either single maker. Conclusions: The miR-221-3p and miR-122-5p are involved in the development of gastric cancer, and they have important clinical values in gastric cancer diagnosis and prognosis.

Dehydroabietic acid inhibits the gastric cancer cell growth via induced apoptosis and cell cycle arrest

김원진,Kang Hyeon-Gu,김석준 대한독성 유전단백체 학회 2021 Molecular & cellular toxicology Vol.17 No.2

Background Gastric cancer is one of the serious malignant tumors with high incidence worldwide. The two commonly used treatment strategies for gastric cancer include chemotherapy and radiation therapy. Conventional anticancer drugs have limited effectiveness. Therefore, it is important to explore new anticancer drugs. Dehydroabietic acid (DAA) is known to have anti-bacterial, anti-inflammatory, and anticancer effects. However, there are fewer reports on the effect of DAA on human gastric cancer cell lines. Objective We investigated the gastric cell growth inhibitory effects of DAA on human gastric cancer cell lines. Gastric cancer cell proliferation, apoptosis and cell cycle arrest assay were detected by WST assay, crystal violet staining assay, Flow cytometry, RT-PCR and western blot analysis. Results These results showed that as the concentration of DAA increased, the proliferation inhibitory effect appeared in gastric cancer cells. In addition, DAA induced sub-G1 phase accumulation and G1 cell cycle arrest, and subsequently induced apoptosis in AGS and YCC-2 cells. In addition, the expression of the pro-apoptotic Bax was upregulated, and that of the anti-apoptotic Bcl-2 was downregulated in DAA-treated AGS and YCC-2 cells. Moreover, DAA induced the cleavage of caspase-3 and PARP. Conclusion These results suggest that DAA induces cell death through mitochondria-mediated apoptosis and G1 cell cycle arrest. Therefore, our results indicate the anticancer and therapeutic potential of DAA for treatment of human gastric cancer. Background Gastric cancer is one of the serious malignant tumors with high incidence worldwide. The two commonly used treatment strategies for gastric cancer include chemotherapy and radiation therapy. Conventional anticancer drugs have limited effectiveness. Therefore, it is important to explore new anticancer drugs. Dehydroabietic acid (DAA) is known to have anti-bacterial, anti-inflammatory, and anticancer effects. However, there are fewer reports on the effect of DAA on human gastric cancer cell lines. Objective We investigated the gastric cell growth inhibitory effects of DAA on human gastric cancer cell lines. Gastric cancer cell proliferation, apoptosis and cell cycle arrest assay were detected by WST assay, crystal violet staining assay, Flow cytometry, RT-PCR and western blot analysis. Results These results showed that as the concentration of DAA increased, the proliferation inhibitory effect appeared in gastric cancer cells. In addition, DAA induced sub-G1 phase accumulation and G1 cell cycle arrest, and subsequently induced apoptosis in AGS and YCC-2 cells. In addition, the expression of the pro-apoptotic Bax was upregulated, and that of the anti-apoptotic Bcl-2 was downregulated in DAA-treated AGS and YCC-2 cells. Moreover, DAA induced the cleavage of caspase-3 and PARP. Conclusion These results suggest that DAA induces cell death through mitochondria-mediated apoptosis and G1 cell cycle arrest. Therefore, our results indicate the anticancer and therapeutic potential of DAA for treatment of human gastric cancer.

미소위암 8예에 대한 임상적 고찰

김영경(Young Kyung Kim),이동기(Dong Ki Lee),이성우(Seong Woo Lee),김준명(Jun Myeong Kim),이상철(Sang Chul Lee),권상옥(Sang Ok Kwon),장우익(Woo Ick Jang),조미연(Mee Yen Cho) 대한소화기학회 1995 대한소화기학회지 Vol.27 No.6

N/A Background/Aims: The aim of this study is to investigate the clinical characteristics of minute gastric cancer, less than 5mm in the largest diameter of the lesion. Methods: We reviewed 8 patients of minute gastric cancer among 100 patients of early gastric cancer(EGC) and 474 patients of advanced gastric cancer who received operation at our hospital from January 1989 to July 1993. Results: The incidence of minute gastric cancer was 8% among early gastric cancer and 1.4% among stomach cancer who received operation. The patients ages ranged from 32 to 74 years old (mean age 60) and most frequently found in their six and seven decade in 75%(6/8). The ratio of male to female was 1.7:1. The multiplicity of minute gastric cancer was 37.5%(3/8), relatively higher than that of EGC 6%(6/100). Before operation we observed 7 lesions of minute gastric cancer by endoscopy. In Suzukis endoscopic classification for minute gastric cancer, most common type of the lesion was depressed type in 4(57.1%), and flat type in 2(28.6%) and elevated type in one(14.2%) patient. The location of minute gastric cancer was antrum in 4, body in 3 and fundus in one. The histologic type of minute gastric cancer was moderate to well differentiated adenocarcinoma in 7, signet ring cell carcinoma in one. The depth of invasion of minute gastric cancer was mucosal cancer in 7, submucosal cancer in one. There was no lymph node metastasis in all minute gastric cancers. Conclusions Almost minute gastric cancers were confined to the mucosa with rare lymph node metastasis. These characteristics of minute gastric cancer may provide the opinion less invasive operation or endoscopic treatment with curative aim. Further study is warranted to assess its significance of endoscopic treatment for minute gastric cancer. (Korean J Gastroenterol 1995;27: 635 - 644)

Microsatellite Instability Is Associated with the Clinicopathologic Features of Gastric Cancer in Sporadic Gastric Cancer Patients

Shin Hyuk Kim,Byung Kyu Ahn,남영수,Joo Youn Pyo1,Young Ha Oh1,이강홍 대한위암학회 2010 Journal of gastric cancer Vol.10 No.4

Purpose: Replication error is an important mechanism in carcinogenesis. The microsatellite instability (MSI-H) of colorectal cancers is associated with the development of multiple cancers. The influence of MSI-H on the development of multiple gastric cancers in sporadic gastric cancer patients has not been defined. This study was performed to reveal the association between the clinicopathologic features and MSI in sporadic gastric cancers. Materials and Methods: Between July 2004 and March 2009, the clinicopathologic characteristics, including MSI status, were evaluated in 128 consecutive patients with sporadic gastric cancers. None of the patients had hereditary non-polyposis colorectal cancer of familial gastric cancer. The markers that were recommended by the NCI to determine the MSI status for colorectal cancers were used. Results: MSI-H cancers were found in 10.9% of the patients (14/128). Synchronous gastric cancers were shown in 4 patients (3.1%). Synchronous cancers were found in 2 of 14 patients with MSI-H gastric cancer (14.3%) and 2 of 114 patients with MSS gastric cancer (1.8%; P=0.059, Fisher's exact test). Among the patients with synchronous cancer 50% (2/4) had MSI-H cancer, but 9.7% of the patients (12/124) without synchronous cancer had MSI-H cancer. MSI-H (RR, 24.7; 95% CI, 1.5~398.9; P=0.024) was related with to synchronous gastric cancer, but age, gender, family history, histologic type, location, gross morphology, size, and stage were not related to synchronous gastric cancer. Conclusions: MSI is associated with the intestinal-type gastric cancer and the presence of multiple gastric cancers in patients with sporadic gastric cancer. Special attention to the presence of synchronous and the development of metachronous multiple cancer in patients with MSI-H gastric cancer is needed.

Microsatellite Instability Is Associated with the Clinicopathologic Features of Gastric Cancer in Sporadic Gastric Cancer Patients

Kim, Shin-Hyuk,Ahn, Byung-Kyu,Nam, Young-Su,Pyo, Joo-Youn,Oh, Young-Ha,Lee, Kang-Hong The Korean Gastric Cancer Association 2010 Journal of gastric cancer Vol.10 No.4

Purpose: Replication error is an important mechanism in carcinogenesis. The microsatellite instability (MSI-H) of colorectal cancers is associated with the development of multiple cancers. The influence of MSI-H on the development of multiple gastric cancers in sporadic gastric cancer patients has not been defined. This study was performed to reveal the association between the clinicopathologic features and MSI in sporadic gastric cancers. Materials and Methods: Between July 2004 and March 2009, the clinicopathologic characteristics, including MSI status, were evaluated in 128 consecutive patients with sporadic gastric cancers. None of the patients had hereditary non-polyposis colorectal cancer of familial gastric cancer. The markers that were recommended by the NCI to determine the MSI status for colorectal cancers were used Results: MSI-H cancers were found in 10.9% of the patients (14/128). Synchronous gastric cancers were shown in 4 patients (3.1%). Synchronous cancers were found in 2 of 14 patients with MSI-H gastric cancer (14.3%) and 2 of 114 patients with MSS gastric cancer (1.8%; P=0.059, Fisher's exact test). Among the patients with synchronous cancer 50% (2/4) had MSI-H cancer, but 9.7% of the patients (12/124) without synchronous cancer had MSI-H cancer. MSI-H (RR, 24.7; 95% CI, 1.5~398.9; P=0.024) was related with to synchronous gastric cancer, but age, gender, family history, histologic type, location, gross morphology, size, and stage were not related to synchronous gastric cancer. Conclusions: MSI is associated with the intestinal-type gastric cancer and the presence of multiple gastric cancers in patients with sporadic gastric cancer. Special attention to the presence of synchronous and the development of metachronous multiple cancer in patients with MSI-H gastric cancer is needed.