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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

Representative immunohistochemical features of seven protein markers including proteins related to leptin signaling pathway (A-G) and in situ hybridization of Epstein-Barr virus encoded small RNAs (H).(A) Leptin shows cytoplasmic expression in cancer cells (x 400). (B) Leptin-receptor exhibits membranous staining in cancer cells (x 200). (C) pSTAT3 shows nuclear staining in cancer cells (x 400). (D) ERK has nuclear positivity in cancer cells (x 400). (E) pAkt shows cytoplasmic or nuclear staining in cancer cells (x 200). (F) mTOR has cytoplasmic positivity in cancer cells (x 200). (G) HIF-1 alpha has cytoplasmic or nuclear staining in cancer cells (x 400). (H) Most of the cancer cells show blue colored nuclear staining on in situ hybridization for Epstein-Barr virus (x 400).
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pone.0130839.g001: Representative immunohistochemical features of seven protein markers including proteins related to leptin signaling pathway (A-G) and in situ hybridization of Epstein-Barr virus encoded small RNAs (H).(A) Leptin shows cytoplasmic expression in cancer cells (x 400). (B) Leptin-receptor exhibits membranous staining in cancer cells (x 200). (C) pSTAT3 shows nuclear staining in cancer cells (x 400). (D) ERK has nuclear positivity in cancer cells (x 400). (E) pAkt shows cytoplasmic or nuclear staining in cancer cells (x 200). (F) mTOR has cytoplasmic positivity in cancer cells (x 200). (G) HIF-1 alpha has cytoplasmic or nuclear staining in cancer cells (x 400). (H) Most of the cancer cells show blue colored nuclear staining on in situ hybridization for Epstein-Barr virus (x 400).

Mentions: Expression of leptin and leptin-receptor were observed in 37% (128/343) and 58% (198/343) of total gastric carcinomas, respectively. Leptin signaling-related proteins were commonly expressed in gastric carcinomas except for pSTAT3; pAkt positive in 79% (271/343) of gastric carcinomas, mTOR in 49% (169/33), HIF-1 alpha in 36% (123/343), ERK in 29% (101/343), and pSTAT3 in 8% (29/343). The representative immunohistochemical staining patterns were shown in Fig 1.


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)

Representative immunohistochemical features of seven protein markers including proteins related to leptin signaling pathway (A-G) and in situ hybridization of Epstein-Barr virus encoded small RNAs (H).(A) Leptin shows cytoplasmic expression in cancer cells (x 400). (B) Leptin-receptor exhibits membranous staining in cancer cells (x 200). (C) pSTAT3 shows nuclear staining in cancer cells (x 400). (D) ERK has nuclear positivity in cancer cells (x 400). (E) pAkt shows cytoplasmic or nuclear staining in cancer cells (x 200). (F) mTOR has cytoplasmic positivity in cancer cells (x 200). (G) HIF-1 alpha has cytoplasmic or nuclear staining in cancer cells (x 400). (H) Most of the cancer cells show blue colored nuclear staining on in situ hybridization for Epstein-Barr virus (x 400).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0130839.g001: Representative immunohistochemical features of seven protein markers including proteins related to leptin signaling pathway (A-G) and in situ hybridization of Epstein-Barr virus encoded small RNAs (H).(A) Leptin shows cytoplasmic expression in cancer cells (x 400). (B) Leptin-receptor exhibits membranous staining in cancer cells (x 200). (C) pSTAT3 shows nuclear staining in cancer cells (x 400). (D) ERK has nuclear positivity in cancer cells (x 400). (E) pAkt shows cytoplasmic or nuclear staining in cancer cells (x 200). (F) mTOR has cytoplasmic positivity in cancer cells (x 200). (G) HIF-1 alpha has cytoplasmic or nuclear staining in cancer cells (x 400). (H) Most of the cancer cells show blue colored nuclear staining on in situ hybridization for Epstein-Barr virus (x 400).
Mentions: Expression of leptin and leptin-receptor were observed in 37% (128/343) and 58% (198/343) of total gastric carcinomas, respectively. Leptin signaling-related proteins were commonly expressed in gastric carcinomas except for pSTAT3; pAkt positive in 79% (271/343) of gastric carcinomas, mTOR in 49% (169/33), HIF-1 alpha in 36% (123/343), ERK in 29% (101/343), and pSTAT3 in 8% (29/343). The representative immunohistochemical staining patterns were shown in Fig 1.

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