The overexpression of MDM4: an effective and novel predictor of gastric adenocarcinoma lymph node metastasis

BACKGROUND and OBJECTIVE: Gastric adenocarcinoma (GAC) is one of the most common malignancies. Increasing data have indicated a correlation between soluble B7-H3 (sB7-H3) levels and tumor malignancies. In this study, we aim to investigate the level of soluble B7-H3 in serum of GAC patients. Further, we analyze the correlation between sB7-H3 level and tissue B7-H3 expression and explore the clinical evaluation value of sB7-H3 associated with pathological characteristics and prognosis of GAC patients. METHODS: One hundred and twenty-eight serum and tissue samples of GAC 20 serum and tissue samples of gastritis patients and 77 serum, 5 tissue samples of healthy controls were collected. The serum levels of sB7-H3 were detected by Enzyme-linked immunosorbent assay (ELISA), while the expression of membrane B7-H3 (mB7-H3) and Ki67 were evaluated by immunohistochemistry. The correlation between sB7-H3 and mB7-H3, sB7-H3 and Ki67, sB7-H3 or mB7-H3 and clinical features were analyzed by Pearson’s Chi-square test. RESULTS: Both serum level of sB7-H3 and tissue B7-H3 of GAC patients were significantly higher than those of gastritis patients and healthy controls. sB7-H3 level was correlated with total B7-H3 expression in tissues (r= 0.2801, P= 0.0014). Notably, the concentration of sB7-H3 was correlated with its expression of membrane form in tumor cells (r= 0.3251, P= 0.002) while not in stromal cells (r= 0.07676, P= 0.3891). Moreover, the levels of sB7-H3 in patients with TNM stage III/IV or with Infiltration depth T3/T4 or with lymph node metastasis were significantly higher than those of patients with TNM stage I/II (P= 0.0020) or with Infiltration depth T1/T2 (P= 0.0169) or with no lymph node metastasis (P= 0.0086). Tumor B7-H3 score, but not stromal B7-H3 score, in patients with TNM stage III/IV or with lymph node metastasis was significantly higher than those with TNM stage I/II (P= 0.0150) or with no lymph node metastasis (P= 0.182). CONCLUSIONS: Soluble B7-H3 level may reflect the tissue B7-H3 expression on tumor cells of GAC tissues. Elevated level of sB7-H3 in serum suggests poor clinical pathological characteristics of GAC patients.

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Expression of bone morphogenic protein-4 is inversely related to prevalence of lymph node metastasis in gastric adenocarcinoma

Surgery Today ◽

10.1007/s00595-010-4320-2 ◽

2011 ◽

Vol 41 (5) ◽

pp. 688-692 ◽

Cited By ~ 6

Author(s):

Seong-Gon Kim ◽

Hye-Rim Park ◽

Soo-Kee Min ◽

Je-Yong Choi ◽

Sung-Hoon Koh ◽

...

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Gastric Adenocarcinoma ◽

Bone Morphogenic Protein ◽

Node Metastasis ◽

Bone Morphogenic Protein 4

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Correlation of histological heterogeneity and lymph node metastasis in gastric adenocarcinoma

World Chinese Journal of Digestology ◽

10.11569/wcjd.v12.i6.1273 ◽

2004 ◽

Vol 12 (6) ◽

pp. 1273 ◽

Cited By ~ 1

Author(s):

Li-Jiang Liu ◽

Xi-Ji Shu ◽

Hong-Yan Zhen ◽

Xiao-Dong Qiu ◽

Hao Deng ◽

...

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Gastric Adenocarcinoma ◽

Node Metastasis ◽

Histological Heterogeneity

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Gastric adenocarcinoma with para-aortic lymph node metastasis: a borderline resectable cancer?

Surgery Today ◽

10.1007/s00595-014-1067-1 ◽

2014 ◽

Vol 45 (9) ◽

pp. 1082-1090 ◽

Cited By ~ 14

Author(s):

Yasuhiro Kodera ◽

Daisuke Kobayashi ◽

Chie Tanaka ◽

Michitaka Fujiwara

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Gastric Adenocarcinoma ◽

Borderline Resectable ◽

Node Metastasis ◽

Aortic Lymph Node ◽

Resectable Cancer

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The Value of Preoperative Neutrophil to Lymphocyte Ratio in Indicating Lymph Node Metastasis in Patients with Resectable T2 Stage Gastric Adenocarcinoma

Clinical Laboratory ◽

10.7754/clin.lab.2015.150824 ◽

2016 ◽

Vol 62 (04/2016) ◽

Cited By ~ 4

Author(s):

Dezhu Zheng ◽

Youdong Yu ◽

Kai Wang ◽

Xiaojuan Ouyang ◽

Yuan Dang ◽

...

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Gastric Adenocarcinoma ◽

Neutrophil To Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Node Metastasis

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Overexpression of cellular FLICE-inhibitory protein (FLIP) in gastric adenocarcinoma

Clinical Science ◽

10.1042/cs20030238 ◽

2004 ◽

Vol 106 (4) ◽

pp. 397-405 ◽

Cited By ~ 47

Author(s):

Xiao-Dong ZHOU ◽

Jie-Ping YU ◽

Jin LIU ◽

He-Sheng LUO ◽

Hong-Xia CHEN ◽

...

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Gastric Mucosa ◽

Gastric Adenocarcinoma ◽

Normal Gastric Mucosa ◽

Inhibitory Protein ◽

Expression Levels ◽

Normal Tissues ◽

Node Metastasis ◽

Gastric Adenocarcinomas

The aim of the present study was to investigate the prevalence of c-FLIP [cellular FLICE-inhibitory protein, where FLICE is Fas-associated death domain (FADD)-like interleukin-1β-converting enzyme] expression in gastric adenocarcinoma and its possible implications for the progression of the cancer. Expression of c-FLIP in 48 gastric adenocarcinomas and their normal counterparts was analysed by reverse transcriptase PCR, Western blotting and immunohistochemistry. In situ cell apoptosis was detected by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay. As a result, c-FLIP transcripts were constitutively expressed in gastric adenocarcinomas and their levels were significantly higher than those in matched normal tissues (P<0.01). Immunohistochemically, the c-FLIP protein was also found to be expressed in all gastric adenocarcinomas (48/48), and 68.8% (33/48) showed an intense immunostaining; in contrast, only 75% (36/48) of normal gastric mucosa showed positive staining and none of them immunostained intensely. The abundance of c-FLIP protein was significantly higher in carcinoma than in normal gastric mucosa (6.93±0.58 versus 3.19±0.26, P<0.01) and showed a reverse correlation with apoptotic index in adenocarcinoma, but not in normal mucosa. In addition, abundance of c-FLIP was significantly associated with lymph node metastasis at both mRNA level (P<0.05) and protein level (P<0.01). Western-blot analysis showed that the expression levels of the long form of c-FLIP and the short form of c-FLIP in adenocarcinomas were 2.6-fold and 2.8-fold (P<0.01) higher than those in normal tissues respectively. However, no significant difference was found between the expression levels of the two isoforms in both adenocarcinomas or normal tissues. In conclusion, overexpression of c-FLIP is tumour specific, which may be one of the in vivo mechanisms by which tumour cells escape from apoptotic death during the malignant transformation, and plays an important role in lymph node metastasis of gastric adenocarcinoma, which ultimately contributes to the tumour progression.

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Evaluation of Lymph Node Metastasis Among Adults With Gastric Adenocarcinoma Managed With Total Gastrectomy

JAMA Network Open ◽

10.1001/jamanetworkopen.2020.35810 ◽

2021 ◽

Vol 4 (2) ◽

pp. e2035810

Author(s):

Harbi Khalayleh ◽

Young-Woo Kim ◽

Hong Man Yoon ◽

Keun Won Ryu ◽

Myeong-Cherl Kook

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Total Gastrectomy ◽

Gastric Adenocarcinoma ◽

Node Metastasis

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TNFAIP8 overexpression is associated with lymph node metastasis and poor prognosis in intestinal-type gastric adenocarcinoma

Histopathology ◽

10.1111/his.12413 ◽

2014 ◽

Vol 65 (4) ◽

pp. 517-526 ◽

Cited By ~ 24

Author(s):

Ming Yang ◽

Qi Zhao ◽

Xiaoxia Wang ◽

Tianbo Liu ◽

Guodong Yao ◽

...

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Gastric Adenocarcinoma ◽

Poor Prognosis ◽

Intestinal Type ◽

Node Metastasis

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Tumor Regression Grade Predicts Survival in Locally Advanced Gastric Adenocarcinoma Patients with Lymph Node Metastasis

Gastroenterology Research and Practice ◽

10.1155/2020/3435673 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Yilin Tong ◽

Yanmei Zhu ◽

Yan Zhao ◽

Zexing Shan ◽

Jianjun Zhang ◽

...

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Gastric Adenocarcinoma ◽

Tumor Regression ◽

Locally Advanced ◽

Prognostic Significance ◽

Tumor Regression Grade ◽

Node Metastasis ◽

Advanced Gastric Adenocarcinoma ◽

Regression Grade

Background. Tumor regression grade (TRG) is widely used in gastrointestinal carcinoma to evaluate pathological responses to neoadjuvant chemotherapy (NCT), but whether it is an independent prognostic factor is still controversial. The aim of this study is to investigate the value of TRG in locally advanced gastric adenocarcinoma patients who underwent NCT and curative resection. Methods. Pathological regression was reevaluated according to the Mandard TRG. Survival curves were obtained by the Kaplan–Meier method, and differences in overall survival (OS) and disease-free survival (DFS) were compared using the log-rank test. Univariate and multivariate analyses for survival were based on the Cox proportional hazards method. Results. In total, 290 patients were identified in our electronic database. In univariable analysis, TRG was associated with OS (HR=3.822, P≤0.001) and DFS (HR=3.374, P≤0.001). However, in multivariable analysis, TRG was not an independent factor for OS (P=0.231) or DFS (P=0.191). In the stratified analysis, TRG retrieved prognostic significance in patients with the metastasis of lymph node (HR=2.034, P=0.035 for OS; HR=2.220, P=0.016 for DFS), while not in patients with negative lymph node (P=0.296 for OS; P=0.172 for DFS). Conclusions. TRG was not an independent predictor for survival, but the system regained its predicting significance in patients with lymph node metastasis.

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