Expression of Angiogenic Proteins in Tumor and Stroma Affects Survival in Patients With Gastric Cancer

被引：6

作者：

Nienhueser, Henrik ^{[1
]}

Crnovrsanin, Nerma ^{[1
]}

Nerz, Daniel ^{[1
]}

Heckler, Max ^{[1
]}

Sisic, Leila ^{[1
]}

Lasitschka, Felix ^{[2
]}

Schneider, Martin ^{[1
]}

Schmidt, Thomas ^{[1
]}

机构：

[1] Heidelberg Univ, Dept Gen Visceral & Transplant Surg, Neuenheimer Feld 110, D-69120 Heidelberg, Germany

[2] Inst Pathol, Ludwigshafen, Germany

来源：

JOURNAL OF SURGICAL RESEARCH | 2020年 / 255卷

关键词：

Gastric cancer; Angiogenesis; Tumor microenvironment; GROWTH-FACTORS; BEVACIZUMAB; VEGF; PLACEBO; MICROENVIRONMENT; CHEMOTHERAPY; MULTICENTER; INDUCTION; THERAPY; PROFILE;

D O I：

10.1016/j.jss.2020.05.045

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

Background: Gastric cancer is one of the most frequent malignancies worldwide. Angiogenic growth factors play a crucial role in mediating the crosstalk between cancer cells and the surrounding microenvironment. In this exploratory study, we investigate the impact of angiogenic proteins within the tumor cell or stroma compartment on survival of patients with gastric cancer. Materials and methods: In 29 patients, tumor and stromal compartments were separated using laser capture microdissection. Angiogenic protein expression was measured using a bead-based immunoassay and correlated with tumor stage and overall survival. Results: Overall survival was significantly shorter in patients with a high stroma concentration of vascular endothelial growth factor (VEGF)-A (23.5 (+/- 17.6) versus 33.6 (+/- 21.0) mo; P = 0.009) and stem cell factor (22.2 (+/- 18.5) versus 33.6 (+/- 21.8) mo; P = 0.01) compared with patients with a low stroma concentration. High stromal VEGF-D showed a trend toward worse survival (26.8 (+/- 22.0) versus 37.2 (+/- 19.0) mo; P = 0.09). We did not observe any significant correlation between tumor-specific expression of angiogenic cytokines and survival. Conclusions: This translational study highlights the difference in clinical impact between tumor and stromal expression of angiogenic proteins. Compartment-specific concentrations of VEGF-A and stem cell factor affect the clinical prognosis and help to identify the best therapy for patients with gastric cancer. (C) 2020 Elsevier Inc. All rights reserved.

引用

页码：172 / 180

页数：9

共 38 条

[1] Prognostic Impacts of Angiopoietins in NSCLC Tumor Cells and Stroma: VEGF-A Impact Is Strongly Associated with Ang-2 [J].

Andersen, Sigve ;

Donnem, Tom ;

Al-Shibli, Khalid ;

Al-Saad, Samer ;

Stenvold, Helge ;

Busund, Lill-Tove ;

Bremnes, Roy M. .

PLOS ONE, 2011, 6 (05)

[2] Tumor stromal vascular endothelial growth factor A is predictive of poor outcome in inflammatory breast cancer [J].

Arias-Pulido, Hugo ;

Chaher, Nabila ;

Gong, Yun ;

Qualls, Clifford ;

Vargas, Jake ;

Royce, Melanie .

BMC CANCER, 2012, 12

[3] Clinical significance of interleukin-6 (IL-6) in the spread of gastric cancer: Role of IL-6 as a prognostic factor [J].

Ashizawa T. ;

Okada R. ;

Suzuki Y. ;

Takagi M. ;

Yamazaki T. ;

Sumi T. ;

Aoki T. ;

Ohnuma S. ;

Aoki T. .

Gastric Cancer, 2005, 8 (2) :124-131

[4]

Bang YJ, 2010, LANCET, V376, P1302

[5] Proposal for a Multifactorial Prognostic Score That Accurately Classifies 3 Groups of Gastric Carcinoma Patients With Different Outcomes After Neoadjuvant Chemotherapy and Surgery [J].

Becker, Karen ;

Reim, Daniel ;

Novotny, Alexander ;

zum Bueschenfelde, Christian Meyer ;

Engel, Jutta ;

Friess, Helmut ;

Hoefler, Heinz ;

Langer, Rupert .

ANNALS OF SURGERY, 2012, 256 (06) :1002-1007

[6] Final efficacy and updated safety results of the randomized phase III BEATRICE trial evaluating adjuvant bevacizumab-containing therapy in triple-negative early breast cancer [J].

Bell, R. ;

Brown, J. ;

Parmar, M. ;

Toi, M. ;

Suter, T. ;

Steger, G. G. ;

Pivot, X. ;

Mackey, J. ;

Jackisch, C. ;

Dent, R. ;

Hall, P. ;

Xu, N. ;

Morales, L. ;

Provencher, L. ;

Hegg, R. ;

Vanlemmens, L. ;

Kirsch, A. ;

Schneeweiss, A. ;

Masuda, N. ;

Overkamp, F. ;

Cameron, D. .

ANNALS OF ONCOLOGY, 2017, 28 (04) :754-760

[7] Inflammatory cytokines are associated with response and prognosis in patients with esophageal cancer [J].

Blank, Susanne ;

Nienhueser, Henrik ;

Dreikhausen, Lena ;

Sisic, Leila ;

Heger, Ulrike ;

Ott, Katja ;

Schmidt, Thomas .

ONCOTARGET, 2017, 8 (29) :47518-47532

[8] Angiogenic and growth factors in gastric cancer [J].

Blank, Susanne ;

Deck, Catrin ;

Dreikhausen, Lena ;

Weichert, Wilko ;

Giese, Natalia ;

Falk, Christine ;

Schmidt, Thomas ;

Ott, Katja .

JOURNAL OF SURGICAL RESEARCH, 2015, 194 (02) :420-429

[9] Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2-3 trial [J].

Cunningham, David ;

Stenning, Sally P. ;

Smyth, Elizabeth C. ;

Okines, Alicia F. ;

Allum, William H. ;

Rowley, Sam ;

Stevenson, Laura ;

Grabsch, Heike I. ;

Alderson, Derek ;

Crosby, Thomas ;

Griffin, S. Michael ;

Mansoor, Wasat ;

Coxon, Fareeda Y. ;

Falk, Stephen J. ;

Darby, Suzanne ;

Sumpter, Kate A. ;

Blazeby, Jane M. ;

Langley, Ruth E. .

LANCET ONCOLOGY, 2017, 18 (03) :357-370

[10] Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial [J].

Fuchs, Charles S. ;

Tomasek, Jiri ;

Yong, Cho Jae ;

Dumitru, Filip ;

Passalacqua, Rodolfo ;

Goswami, Chanchal ;

Safran, Howard ;

dos Santos, Lucas Vieira ;

Aprile, Giuseppe ;

Ferry, David R. ;

Melichar, Bohuslav ;

Tehfe, Mustapha ;

Topuzov, Eldar ;

Zalcberg, John Raymond ;

Chau, Ian ;

Campbell, William ;

Sivanandan, Choondal ;

Pikiel, Joanna ;

Koshiji, Minori ;

Hsu, Yanzhi ;

Liepa, Astra M. ;

Gao, Ling ;

Schwartz, Jonathan D. ;

Tabernero, Josep .

LANCET, 2014, 383 (9911) :31-39

← 1 2 3 4 →