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Implication of Leptin-Signaling Proteins and Epstein-Barr Virus in Gastric Carcinomas.

Choi E, Byeon SJ, Kim SH, Lee HJ, Kwon HJ, Ahn H, Kim DH, Chang MS - PLoS ONE (2015)

Bottom Line: Additionally, in stomach cancer cells, cleaved caspase 3 level increased by leptin-receptor inhibition, that is, apoptosis increased.Interestingly, EBV-positive AGC (n = 29) tended to show better survival of patients than EBV-negative AGC (n = 178) (P = 0.06). pAkt expression was related with a good survival of 32 patients (9%) in the EBV-positive subgroup, but was not an independent prognostic factor.The leptin-receptor may predict poor patient prognosis in the AGC, Lauren diffuse and lymph node metastasis subgroups, while EBV-positive status can show a good prognosis in the AGC.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea.

ABSTRACT
We investigated the clinicopathological implications of leptin-signaling proteins and Epstein-Barr virus (EBV)-infection status in gastric carcinomas. Immunohistochemistry for leptin signalling-related proteins (leptin, leptin-receptor, pSTAT3, ERK, pAkt, mTOR and HIF-1 alpha), and in situ hybridization for EBV-encoded small RNAs was performed in 343 cases of gastric carcinomas. The siRNA against leptin-receptor was transfected into three stomach cancer cell lines, and western blot for caspase 3 was performed. The TNM stage was a prognostic factor in all 343 patients, and was negatively correlated with expression of leptin, pSTAT3, ERK, pAkt, mTOR and HIF-1 alpha (P < 0.05). Leptin-receptor expression was correlated with poor survival in 207 patients of the advanced gastric cancer (AGC) subgroup, 139 of the Lauren diffuse group, and in 160 patients with lymph node metastasis (P < 0.05, respectively). Additionally, in stomach cancer cells, cleaved caspase 3 level increased by leptin-receptor inhibition, that is, apoptosis increased. Interestingly, EBV-positive AGC (n = 29) tended to show better survival of patients than EBV-negative AGC (n = 178) (P = 0.06). pAkt expression was related with a good survival of 32 patients (9%) in the EBV-positive subgroup, but was not an independent prognostic factor. Among, leptin signaling-related proteins, expressions of leptin-receptor and mTOR were different between EBV-positive subgroup and EBV-negative subgroup (P < 0.05, respectively). In conclusion, leptin-signaling proteins and EBV status show different significance on patient survival, according to subsets of gastric carcinomas. The leptin-receptor may predict poor patient prognosis in the AGC, Lauren diffuse and lymph node metastasis subgroups, while EBV-positive status can show a good prognosis in the AGC. Each leptin signaling-related protein may be differently involved in carcinogenesis of EBV-negative and EBV-positive subsets.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier survival curves in each group of gastric carcinomas according to leptin-receptor expression status (A-D).(A) Advanced TNM stage was associated with poor survival of patients in all cases of gastric carcinoma (n = 343) (P < 0.001). (B) Leptin-receptor positivity was related with unfavorable survival outcome in the advanced gastric carcinoma subgroup (n = 207) (P = 0.015). (C) Leptin-receptor positivity was correlated with poor survival rate in the diffuse-type gastric carcinoma subgroup (n = 139) (P = 0.007). (D) Leptin-receptor positivity was compatible with lower survival rate in patients with lymph node metastasis (n = 160) (P = 0.023).
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pone.0130839.g002: Kaplan-Meier survival curves in each group of gastric carcinomas according to leptin-receptor expression status (A-D).(A) Advanced TNM stage was associated with poor survival of patients in all cases of gastric carcinoma (n = 343) (P < 0.001). (B) Leptin-receptor positivity was related with unfavorable survival outcome in the advanced gastric carcinoma subgroup (n = 207) (P = 0.015). (C) Leptin-receptor positivity was correlated with poor survival rate in the diffuse-type gastric carcinoma subgroup (n = 139) (P = 0.007). (D) Leptin-receptor positivity was compatible with lower survival rate in patients with lymph node metastasis (n = 160) (P = 0.023).

Mentions: Patient outcome (median follow-up period: 77 months) was mortality in 148 of the total 343 (43%) patients, which included 10 of the 32 EBV-positive group (31%) patients. pTNM stage was the absolute independent prognostic factor, on univariate and multivariate analyses in all 343 patients (P < 0.05) (Fig 2A). None of the examined protein markers (leptin, leptin- receptor, pSTAT3, ERK, pAkt, mTOR and HIF-1 alpha) alone, had a statistical significance on overall survival in all 343 patients on multivariate analysis.


Implication of Leptin-Signaling Proteins and Epstein-Barr Virus in Gastric Carcinomas.

Choi E, Byeon SJ, Kim SH, Lee HJ, Kwon HJ, Ahn H, Kim DH, Chang MS - PLoS ONE (2015)

Kaplan-Meier survival curves in each group of gastric carcinomas according to leptin-receptor expression status (A-D).(A) Advanced TNM stage was associated with poor survival of patients in all cases of gastric carcinoma (n = 343) (P < 0.001). (B) Leptin-receptor positivity was related with unfavorable survival outcome in the advanced gastric carcinoma subgroup (n = 207) (P = 0.015). (C) Leptin-receptor positivity was correlated with poor survival rate in the diffuse-type gastric carcinoma subgroup (n = 139) (P = 0.007). (D) Leptin-receptor positivity was compatible with lower survival rate in patients with lymph node metastasis (n = 160) (P = 0.023).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493019&req=5

pone.0130839.g002: Kaplan-Meier survival curves in each group of gastric carcinomas according to leptin-receptor expression status (A-D).(A) Advanced TNM stage was associated with poor survival of patients in all cases of gastric carcinoma (n = 343) (P < 0.001). (B) Leptin-receptor positivity was related with unfavorable survival outcome in the advanced gastric carcinoma subgroup (n = 207) (P = 0.015). (C) Leptin-receptor positivity was correlated with poor survival rate in the diffuse-type gastric carcinoma subgroup (n = 139) (P = 0.007). (D) Leptin-receptor positivity was compatible with lower survival rate in patients with lymph node metastasis (n = 160) (P = 0.023).
Mentions: Patient outcome (median follow-up period: 77 months) was mortality in 148 of the total 343 (43%) patients, which included 10 of the 32 EBV-positive group (31%) patients. pTNM stage was the absolute independent prognostic factor, on univariate and multivariate analyses in all 343 patients (P < 0.05) (Fig 2A). None of the examined protein markers (leptin, leptin- receptor, pSTAT3, ERK, pAkt, mTOR and HIF-1 alpha) alone, had a statistical significance on overall survival in all 343 patients on multivariate analysis.

Bottom Line: Additionally, in stomach cancer cells, cleaved caspase 3 level increased by leptin-receptor inhibition, that is, apoptosis increased.Interestingly, EBV-positive AGC (n = 29) tended to show better survival of patients than EBV-negative AGC (n = 178) (P = 0.06). pAkt expression was related with a good survival of 32 patients (9%) in the EBV-positive subgroup, but was not an independent prognostic factor.The leptin-receptor may predict poor patient prognosis in the AGC, Lauren diffuse and lymph node metastasis subgroups, while EBV-positive status can show a good prognosis in the AGC.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea.

ABSTRACT
We investigated the clinicopathological implications of leptin-signaling proteins and Epstein-Barr virus (EBV)-infection status in gastric carcinomas. Immunohistochemistry for leptin signalling-related proteins (leptin, leptin-receptor, pSTAT3, ERK, pAkt, mTOR and HIF-1 alpha), and in situ hybridization for EBV-encoded small RNAs was performed in 343 cases of gastric carcinomas. The siRNA against leptin-receptor was transfected into three stomach cancer cell lines, and western blot for caspase 3 was performed. The TNM stage was a prognostic factor in all 343 patients, and was negatively correlated with expression of leptin, pSTAT3, ERK, pAkt, mTOR and HIF-1 alpha (P < 0.05). Leptin-receptor expression was correlated with poor survival in 207 patients of the advanced gastric cancer (AGC) subgroup, 139 of the Lauren diffuse group, and in 160 patients with lymph node metastasis (P < 0.05, respectively). Additionally, in stomach cancer cells, cleaved caspase 3 level increased by leptin-receptor inhibition, that is, apoptosis increased. Interestingly, EBV-positive AGC (n = 29) tended to show better survival of patients than EBV-negative AGC (n = 178) (P = 0.06). pAkt expression was related with a good survival of 32 patients (9%) in the EBV-positive subgroup, but was not an independent prognostic factor. Among, leptin signaling-related proteins, expressions of leptin-receptor and mTOR were different between EBV-positive subgroup and EBV-negative subgroup (P < 0.05, respectively). In conclusion, leptin-signaling proteins and EBV status show different significance on patient survival, according to subsets of gastric carcinomas. The leptin-receptor may predict poor patient prognosis in the AGC, Lauren diffuse and lymph node metastasis subgroups, while EBV-positive status can show a good prognosis in the AGC. Each leptin signaling-related protein may be differently involved in carcinogenesis of EBV-negative and EBV-positive subsets.

No MeSH data available.


Related in: MedlinePlus