CANCER-ASSOCIATED ADIPOCYTES AND PROGNOSTIC VALUE OF PREOPERATIVE NEUTROPHIL-LYMPHOCYTE RATIO IN GASTRIC CANCER

Authors

  • L. Bubnovskaya R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • I. Ganusevich R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • S. Merentsev Kyiv City Clinical Oncology Center
  • D. Osinsky Kyiv City Clinical Oncology Center

DOI:

https://doi.org/10.15407/exp-oncology.2023.01.088

Keywords:

BMI, cancer-associated adipocytes, gastric cancer, prognostic value of NLR

Abstract

Background: The neutrophil-to-lymphocyte ratio (NLR) turned out to be a routinely available marker capable to reflect the systemic inflammatory response created by a tumor. Gastric cancer (GC) grows in the anatomical vicinity of adipose tissue, which is also associated with low-grade inflammation. Aim: To investigate the usefulness of the combined use of preoperative NLR and density of intratumoral cancer-associated adipocytes (CAAs) for predicting the disease outcome in GC patients. Materials and Methods: A total of 151 patients with GC were eligible for retrospective analysis between 2009 and 2015.NLR preoperative values were calculated. Perilipin expression in tumor tissue was examined immunohistochemically. Results: Low preoperative NLR is the most reliable prognostic factor for the favorable outcome for patients with low density of intratumoral CAAs. Patients with a high density of CCAs are at high risk of lethal outcomes independently of the value of preoperative NLR. Conclusion: The results have clearly shown an association between preoperative NLR and the density of CAAs in the primary tumor of GC patients. The prognostic value of NLR is essentially modified by means of the individual density of intratumoral CAAs in GC patients.The elevated NLR could be of significant predictive potential for a negative prognosis for patients with tumors characterized by the high density of CAAs independently of BMI.

References

Shacter E, Weitzman SA. Chronic inflammation and cancer. Oncology (Williston Park) 2002; 16: 217–226, 229.

Song X-D, Wang Y-N, Zhang A-L, Liu B. Advances in research on the interaction between inflammation and cancer. J Int Med Res 2020;48: 300060519895347 doi.10.1177/0300060519895347

Gou M, Qu T, Wang Z, et al. Neutrophil-to-lymphocyte ratio (NLR) predicts PD-1 inhibitor survival in patients with metastatic gastric cancer. J Immunol Res 2021; 2021. doi: 10.1155/2021/2549295

Xiong S, Dong L, Cheng L.Neutrophils in cancer carcinogenesis and metastasis. J Hematol Oncol 2021; 14: 173. doi: 10.1186/s13045-021-01187-y

Sharaiha RZ, Halazun KJ, Mirza F, et al. Elevated preoperative neutrophil:lymphocyte ratio as a predictor of postoperative disease recurrence in esophageal cancer. Ann Surg Oncol 2011;18: 3362–3369. doi: 10.1245/s10434-011-1754-8

Scilla KA, Bentzen SM, Lam VK, et al. Neutrophil-lymphocyte ratio is a prognostic marker in patients with locally advanced (stage IIIA and IIIB) non-small cell lung cancer treated with combined modality therapy. Oncologist 2017; 22: 737–742. doi: 10.1634/theoncologist.2016-0443

Zhao Z, Zhao X, Lu J , et al. Prognostic roles of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in ovarian cancer: a meta-analysis of retrospective studies. Arch Gynecol Obstet 2018; 297: 849–857. doi: 10.1007/s00404-018-4678-8

Hu H, Yao X, Xie X, et al. Prognostic value of preoperative NLR, dNLR, PLR and CRP in surgical renal cell carcinoma patients. World J Urol 2017; 35: 261–270. doi: 10.1007/s00345-016-1864-9

Fumei Yi, Yangchun Gu, Sen Chen, et al. Impact of the pretreatment or posttreatment NLR and PLR on the response of first line chemotherapy and the outcomes in patients with advanced non-small cell lung cancer. Zhongguo Fei Ai Za Zhi 2018; 21: 481–492. doi: 10.3779/j.issn.1009-3419.2018.06.02

Xie X, Luo KJ, Hu Y, et aL. Prognostic value of preoperative platelet-lymphocyte and neutrophil-lymphocyte ratio in patients undergoing surgery for esophageal squamous cell cancer. Dis Esophagus 2016; 29: 79–85.doi: 10.1111/dote.12296

Miao Y, Yan Q, Li S, et al. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio are predictive of chemotherapeutic response and prognosis in epithelial ovarian cancer patients treated with platinum-based chemotherapy. Cancer Biomark 2016; 17: 33–40. doi: 10.3233/CBM-160614

Grenader T, Nash S, Adams R. Derived neutrophil lymphocyte ratio is predictive of survival from intermittent therapy in advanced colorectal cancer: a post hoc analysis of the MRC COIN study. Brit J Can 2016; 114, 612–615. doi: 10.1038/bjc.2016.23 www.bjcancer.com

Zhang Y, Jiang C, Li J, et al. Prognostic significance of preoperative neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in patients with gallbladder carcinoma. Clin Transl Oncol 2015; 17: 810–818. doi: 10.1007/s12094-015-1310-2

Tao Z, Li SX, Cui X, et al. The prognostic value of preoperative inflammatory indexes in gallbladder carcinoma with hepatic involvement. Cancer Biomark 2018; 22:551–557. doi: 10.3233/CBM-181230

Hooper L, Abdelhamid A, Bunn D, Brown T, et al. Effects of total fat intake on body weight. Cochrane Database Syst Rev 2015; CD011834

Mapping the health system response to childhood obesity in the WHO European Region. An overview and country perspectives (2019). Available from: https://apps.who.int/iris/bitstream/handle/10665/346468/WHO-EURO-2019-3656-43415-60957-eng.pdf?sequence=1&isAllowed=y

Nigro E, Scudiero O, Monaco ML, et al. New insight into adiponectin role in obesity and obesity-related diseases. Biomed Res Int 2014; 2014: 658913. doi: 10.1155/2014/658913

Goossens GH, Blaak EE. Adipose tissue dysfunction and impaired metabolic health in human obesity: a matter of oxygen. Front Endocrinol (Lausanne) 2015; 6: 1–5

Colditz G, Peterson L. Obesity and cancer: evidence, impact, and future directions. Clin Chem 2018; 64: 154–162. doi: 10.1373/clinchem.2017.277376

Alexandre L, Long E, Beales L. Pathophysiological mechanisms linking obesity and esophageal adenocarcinoma. World J Gastrointest Pathophysiol 2014; 5: 534–549. doi: 10.4291/wjgp.v5.i4.534

Blackburn H, Jacobs D. Commentary: Origins and evolution of body mass index (BMI): continuing saga. Int J Epidemiol 2014; 43: 665–669. doi: 10.1093/ije/dyu061

Nuttall FQ. Body mass index: obesity, BMI, and health: A critical review Nutr Today 2015; 50: 117–128. doi: 10.1097/NT.0000000000000092

Reaves DK, Ginsburg E, Bang JJ, et al. Persistent organic pollutants & obesity: potential mechanisms for breast cancer promotion? Endocr Relat Cancer 2015; 22: R69–R86. doi: 10.1530/ERC-14-0411

Wu H, Ballantyne CM. metabolic inflammation and insulin resistance in obesity.Circ Res 2020; 126: 1549–1564. doi: 10.1161/CIRCRESAHA.119.315896

Nurul M, Hussain AS, Sarwar S, et al. How the association between obesity and inflammation may lead to insulin resistance and cancer. 2019; 13: 1213–1224. doi: 10.1016/j.dsx.2019.01.041

International Union Against Cancer, TNM Classification of Malignant Tumors Ed. by L.H. Sobin and C. Wittekind. New York: Wiley-Liss, 6th ed. 2002.

Fenoglio-Preiser C, Carneiro F, Correa P, et al. Gastric Carcinoma, in World Health Organization Classification of Tumors. Tumours of the Stomach. Ed. by S.R. Hamilton, L.A. Aaltonen. IARC Press, Lyon, France, 2000; 3, Ch. 3: 39–52

Bubnovskaya L, Mikhailenko V, Merentsev S, Osinsky D. Tumor-infiltrating lymphocytes in primary tumor and bone marrow in patients with gastric cancer and overweight. J Pharmacy Pharmacol 2019; 7: 611–620. doi: 10.17265/2328-2150/2019.12.002

Bubnovskaya L, Ganusevich I, Merentsev S, Osinsky D. Research on disseminated tumor cells in bone marrow in gastric cancer patients with obesity. Innovations Medicine Med Res 2020; 3: 142–150. doi: 10.9734/bpi/immr/v3

Bubnovskaya L, Ganusevich I, Merentsev S, Osinsky D. Adipocytes as a risk factor for metastasis in patients with gastric cancer and normal weight. Curr Pract Med Sci 2022; 5: 37–46. doi: 10.9734/bpi/cpms/v5/6831F

Zhao G , Liu N, Wang S, et al. Prognostic significance of the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio in patients with metastatic gastric cancer. Medicine (Baltimore) 2020; 99: e19405. doi: 10.1097/MD.0000000000019405.

Zhang Y, Lu JJ, Du YP, et al. Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in gastric cancer. Medicine (Baltimore) 2018; 97: e0144. doi: 10.1097/MD.0000000000010144

Zhang LX, Wei ZJ, Xu AM, Zang JH. Can the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio be beneficial in predicting lymph node metastasis and promising prognostic markers of gastric cancer patients? Tumor maker retrospective study. Int J Surg 2018; 56: 320–327. doi: 10.1016/j.ijsu.2018.06.037

Zhu GS, Tian SB, Wang H, et al. Preoperative neutrophil lymphocyte ratio and platelet lymphocyte ratio cannot predict lymph node metastasis and prognosis in patients with early gastric cancer: a single institution investigation in China. Curr Med Sci 2018; 38: 78–84. doi: 10.1007/s11596-018-1849-6

Sun X, Liu X, Liu J, et al. Preoperative neutrophil-to-lymphocyte ratio plus platelet-to-lymphocyte ratio in predicting survival for patients with stage I–II gastric cancer. Chin J Cancer 2016; 35: 57. doi: 10.1186/s40880-016-0122-2

Zeyao Ye , Pengfei Yu , Yang Cao, et al. Prediction of peritoneal cancer index and prognosis in peritoneal metastasis of gastric cancer using NLR-PLR-DDI Score: a retrospective study. Cancer Manag Res 2022; 14: 177–187. doi: 10.2147/CMAR.S343467

Liu D, Jin J, Zhang L, et al. The neutrophil to lymphocyte ratio may predict benefit from chemotherapy in lung cancer cell. Physiol Biochem 2018; 46: 1595–1605. doi: 10.1159/000489207

Graeme J K Guthrie 1 , Kellie A Charles, Campbell S D Roxburgh, et al. The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer Crit Rev Oncol Hematol 2013; 88: 218–230. doi: 10.1016/j.critrevonc.2013.03.010

Deng M, Ma X, Liang X, et al. Are pretreatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio useful in predicting the outcomes of patients with small-cell lung cancer? Oncotarget 2017; 8: 37200–37207. doi: 10.18632/oncotarget.16553.

Yodying H, Matsuda A, Miyashita M, et al. Prognostic significance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in oncologic outcomes of esophageal cancer: A systematic review and meta-analysis. Ann Surg Oncol 2016; 23, 646–654. doi: 10.1245/s10434-015-4869-5

Jung J, Park SY, Park SJ, Park J. Prognostic value of the neutrophil-to-lymphocyte ratio for overall and disease-free survival in patients with surgically treated esophageal squamous cell carcinoma. Tumour Biol 2016; 37: 7149–7154. doi: 10.1007/s13277-015-4596-3

Jin X, Wang K, Shao X, Huang J. Prognostic implications of the peripheral platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in predicting pathologic complete response after neoadjuvant chemotherapy in breast cancer patients. Gland Surg 2022; 11: 1057–1066. doi: 10.21037/gs-22-244

Dupré A, Malik HZ. Inflammation and cancer: What a surgical oncologist should know. Eur J Surg Oncol 2018; 44: 566–570. doi.10.1016/j.ejso.2018.02.209

Shirai Y, Shiba H, Haruki K, et al. Preoperative platelet-to-albumin ratio predicts prognosis of patients with pancreatic ductal adenocarcinoma after pancreatic resection. Anticancer Res 2017; 37: 787–793. doi: 10.21873/anticanres.11378

Lin JX, Lin JP, Xie JW, et al. Prognostic importance of the preoperative modified systemic inflammation score for patients with gastric cancer. Gastric Cancer 2019; 22: 403–412. doi: 10.1007/s10120-018-0854-6

Xu S-S, Li S, Xu HX, et al. Haemoglobin, albumin, lymphocyte and platelet predicts postoperative survival in pancreatic cancer. World J Gastroenterol 2020; 26: 828–838. doi: 10.3748/wjg.v26.i8.828

Clinical value of hemoglobin and albumin levels and lymphocyte and platelet count (HALP) combination in predicting postoperative complications, lymph node positivity and prognosis in gastric cancer patients who underwent curative surgical resection. Cyprus J Med Sci 2020; 5: 145–152. doi:10.5152/cjms.2020.1747

Yalav O, Topal U, Unal AG, Eray IC. Prognostic significance of preoperative hemoglobin and albumin levels and lymphocyte and platelet counts (HALP) in patients undergoing curative resection for colorectal cancer. Ann Ital Chir 2021; 92: 283–292.

Shen XB, Zhang YX, Wang W, Pan YY. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score in patients with small cell lung cancer before first-line treatment with etoposide and progression-free survival. Int Med J Exp Clin Res 2019; 25: 5630–5639.doi:10.12659/MSM.917968

Loosen, SH, Roderburg C, Jördens MS, et al. Overweight and obesity determine the risk for gastrointestinal cancer in a sex-dependent manner: a retrospective cohort study of 287, 357 outpatients in Germany. Cancers 2022, 14: 931. doi: 0.3390/cancers14040931

Brown JC, Meyerhardt JA. Obesity and energy balance in GI Cancer. J Clin Oncol 2016; 34; 4217–4224. doi: 10.1200/JCO.2016.66.8699

Ye Z, Wei S, Zeng Y, et al. Prognostic value of preoperative body mass index for diabetic patients with non-metastasis gastric cancer: a single center experience. BMC Surg; 21: 320. doi: 10.1186/s12893-021-01316-x

Gu L, Zhang Y, Hong J, et al. Prognostic value of pretreatment overweight/obesity and adipose tissue distribution in resectable gastric cancer: a retrospective cohort study. Front Oncol 2021; 11: 680190. doi: 10.3389/fonc.2021.680190

Cozzo AJ, Fuller AM, Makowski L. Contribution of adipose tissue to development of cancer. Dental Press J Orthod 2017; 3: 21–25. doi: 10.1002/cphy.c170008

Kyrgiou, M. Kalliala I, Markozannes G, Gunter MJ. Adiposity and cancer at major anatomical sites: umbrella review of the literature. BMJ 2017; 356: j477. doi: 10.1136/bmj.j47

Nieman KM, Romero IL, Van Houten B, Lengyel E. Adipose tissue and adipocytes support tumorigenesis and metastasis. Biochim Biophys Acta 2013; 1831:1533–1541. doi: 10.1016/j.bbalip.2013.02.010

O’Sullivan J, Lysaght J, Donohoe CL, Reynolds JV. Obesity and gastrointestinal cancer: the interrelationship of adipose and tumour microenvironment. Nat Rev Gastroenterol Hepatol 2018; 15: 699–714. doi: 10.1038/s41575-018-0069-7

Xiang F, Wu K, Liu Y, et al. Omental adipocytes enhance the invasiveness of gastric cancer cells by oleic acid-induced activation of the PI3K-Akt signaling pathway. Int J Biochem Cell Biol 2017; 84: 14–21. doi:10.1016/j.biocel.2016.12.002

Kane H., Lynch L. Innate immune control of adipose tissue homeostasis. Trends Immunol 2019; 40: 857–872. doi: 10.1016/j.it.2019.07.006

Trim WV, Lynch L. Immune and non-immune functions of adipose tissue leukocytes. Nat Rev Immunol 2022; 22: 371–386. doi: 10.1038/s41577-021-00635-7

Guilherme A, Virbasius JV, Puri V, Czech MP. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol 2008; 9: 367–377. doi: 10.1038/nrm2391

Quail DF, Olson OC, Bhardwaj P, et al. Obesity alters the lung myeloid cell landscape to enhance breast cancer metastasis through IL5 and GM-CSF. Nat Cell Biol 2017; 19: 974–987. doi: 10.1038/ncb3578

Deng T, Lyon CJ, Bergin S, et al. Obesity, inflammation, and cancer. Annu Rev Pathol 2016; 11: 421–449. doi: 10.1146/annurev-pathol-012615-044359

Downloads

Published

26.06.2023

How to Cite

Bubnovskaya, L., Ganusevich, I., Merentsev, S., & Osinsky, D. (2023). CANCER-ASSOCIATED ADIPOCYTES AND PROGNOSTIC VALUE OF PREOPERATIVE NEUTROPHIL-LYMPHOCYTE RATIO IN GASTRIC CANCER. Experimental Oncology, 45(1), 88–98. https://doi.org/10.15407/exp-oncology.2023.01.088

Issue

Section

Original contributions