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Systemic Immune-Inflammation Index Predicts Overall Survival in Patients with Gastric Cancer: a Propensity Score–Matched Analysis

  • Original Article
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Journal of Gastrointestinal Surgery

Abstract

Background

The systemic immune-inflammation index (SII), integrated by peripheral lymphocyte, neutrophil, and platelet counts, is used as an objective biomarker that reflects the balance between host inflammatory and immune response status in cancer patients. Herein, we examined the prognostic significance of SII in gastric cancer patients.

Methods

We retrospectively reviewed data of 415 patients who underwent curative laparoscopic gastrectomy using propensity score–matched (PSM) analysis. The prognostic value of SII was compared between two groups based on SII values: low SII group (SII < 661.9) and high SII group (SII ≥ 661.9).

Results

In multivariate analysis, the American Society of Anesthesiologists physical status (ASA-PS) (p < 0.001), tumor differentiation (p = 0.019), pathological stage (p = 0.046), carcinoembryonic antigen (CEA) level (p < 0.001), SII (p = 0.006), and operative procedure (p = 0.009) were independent prognostic factors of overall survival (OS) in the overall PSM cohort. The log-rank test demonstrated that patients with a high SII had significantly worse OS than did those with low SII (p = 0.002). In age-stratified subgroups analysis (< 65/≥ 65 years), multivariate analysis revealed that ASA-PS (p < 0.001), tumor differentiation (p = 0.019), CEA level (p = 0.008), SII (p = 0.013), and operative procedure (p = 0.026) were independent prognostic factors of OS in the elderly group. Similarly, elderly patients with a high SII had significantly worse OS than did those with a low SII (p = 0.009). Meanwhile, SII was not an independent prognostic factor of OS, and no significant association was observed between SII and OS in non-elderly patients.

Conclusions

SII was an independent prognostic indicator in gastric cancer patients, especially in the elderly population.

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References

  1. Farrow B, Sugiyama Y, Chen A, Uffort E, Nealon W, Mark Evers B. Inflammatory mechanisms contributing to pancreatic cancer development. Ann Surg 2004;239:763-769; discussion 769-771.

    Article  Google Scholar 

  2. Mimatsu K, Fukino N, Ogasawara Y, Saino Y, Oida T. Utility of inflammatory marker- and nutritional status-based prognostic factors for predicting the prognosis of stage IV gastric cancer patients undergoing non-curative surgery. Anticancer Res 2017;37:4215-4222.

    PubMed  Google Scholar 

  3. Yun JK, McCormick TS, Villabona C, Judware RR, Espinosa MB, Lapetina EG. Inflammatory mediators are perpetuated in macrophages resistant to apoptosis induced by hypoxia. Proc Natl Acad Sci U S A 1997;94:13903-13908.

    Article  CAS  Google Scholar 

  4. Hirahara N, Matsubara T, Mizota Y, Ishibashi S, Tajima Y. Prognostic value of preoperative inflammatory response biomarkers in patients with esophageal cancer who undergo a curative thoracoscopic esophagectomy. BMC Surg 2016;16:66. doi: https://doi.org/10.1186/s12893-016-0179-5.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Shimizu T, Taniguchi K, Asakuma M, Tomioka A, Inoue Y, Komeda K, Hirokawa F, Uchiyama K. Lymphocyte-to-monocyte ratio and prognostic nutritional index predict poor prognosis in patients on chemotherapy for unresectable pancreatic cancer. Anticancer Res 2019;39:2169-2176. doi: https://doi.org/10.21873/anticanres.13331.

    Article  CAS  PubMed  Google Scholar 

  6. Hu B, Yang XR, Xu Y, Sun YF, Sun C, Guo W, Zhang X, Wang WM, Qiu SJ, Zhou J, Fan J. Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res 2014;20:6212-6222.

    Article  CAS  Google Scholar 

  7. Cancer Research UK [Internet]. Available: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics

  8. Hartgrink HH, Jansen EP, van Grieken NC, van de Velde CJ. Gastric cancer. Lancet 2009;374:477-490. doi: https://doi.org/10.1016/S0140-6736(09)60617-6.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2014 (ver. 4). Gastric Cancer 2017;20:1-19. https://doi.org/10.1007/s10120-016-0622-4.

    Article  Google Scholar 

  10. Sobin L, Gospodarowicz M, Wittekind C, editors. International Union against Cancer (UICC). TNM classification of malignant tumors, 7th ed. New York: Wiley-Blackwell, 2010.

    Google Scholar 

  11. Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibañes E, Pekolj J, Slankamenac K, Bassi C, Graf R, Vonlanthen R, Padbury R, Cameron JL, Makuuchi M. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg 2009;250:187-196. https://doi.org/10.1097/SLA.0b013e3181b13ca2.

    Article  PubMed  Google Scholar 

  12. Dupré A, Jones RP, Diaz-Nieto R, Fenwick SW, Poston GJ, Malik HZ. Preoperative leucocyte-based inflammatory scores in patients with colorectal liver metastases: Can we count on them? World J Surg 2019;43:1351-1359. doi: https://doi.org/10.1007/s00268-019-04914-2.

    Article  PubMed  Google Scholar 

  13. Xu F, Xu P, Cui W, Gong W, Wei Y, Liu B, Dong J. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios may aid in identifying patients with non-small cell lung cancer and predicting tumor-node-metastasis stages. Oncol Lett 2018;16:483-490. doi: https://doi.org/10.3892/ol.2018.8644.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Huang Z, Liu Y, Yang C, Li X, Pan C, Rao J, Li N, Liao W, Lin L. Combined neutrophil/platelet/lymphocyte/differentiation score predicts chemosensitivity in advanced gastric cancer. BMC Cancer 2018;18:515. doi: https://doi.org/10.1186/s12885-018-4414-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lu Y, Xin D, Wang F. Predictive significance of preoperative systemic immune-inflammation index determination in postoperative liver metastasis of colorectal cancer. Onco Targets Ther 2019;20;12:7791-7799. doi: https://doi.org/10.2147/OTT.S223419.

    Article  Google Scholar 

  16. Zhong JH, Huang DH, Chen ZY. Prognostic role of systemic immune-inflammation index in solid tumors: a systematic review and meta-analysis. Oncotarget 2017;8:75381-75388. doi: https://doi.org/10.18632/oncotarget.18856.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Wang L, Wang C, Wang J, Huang X, Cheng Y. A novel systemic immune-inflammation index predicts survival and quality of life of patients after curative resection for esophageal squamous cell carcinoma. J Cancer Res Clin Oncol 2017;143:2077-2086. doi: https://doi.org/10.1007/s00432-017-2451-1.

    Article  PubMed  Google Scholar 

  18. Nakano Y, Uchiyama M, Arima T, Nagasaka S, Igarashi T, Shimizu A, Takahashi H. PPARα Agonist suppresses inflammation after corneal alkali burn by suppressing proinflammatory cytokines, MCP-1, and nuclear translocation of NF-κB. Molecules 2018;24. E114. doi: https://doi.org/10.3390/molecules24010114.

    Article  CAS  PubMed  Google Scholar 

  19. Yang HL, Huang PJ, Liu YR, Kumar KJ, Hsu LS, Lu TL, Chia YC, Takajo T, Kazunori A, Hseu YC. Toona sinensis inhibits LPS-induced inflammation and migration in vascular smooth muscle cells via suppression of reactive oxygen species and NF-κB signaling pathway. Oxid Med Cell Longev 2014:901315. doi: https://doi.org/10.1155/2014/901315.

  20. Gao Z, Tong C, Wang Y, Chen D, Wu Z, Han W. Blocking CD38-driven fratricide among T cells enables effective antitumor activity by CD38-specific chimeric antigen receptor T cells. J Genet Genomics 2019;46:367-377. doi: https://doi.org/10.1016/j.jgg.2019.06.007.

    Article  PubMed  Google Scholar 

  21. Liu L, Zou J, Guan Y, Zhang Y, Zhang W, Zhou X, Xiong C, Tolbert E, Zhao TC, Bayliss G, Zhuang S. Blocking the histone lysine 79 methyltransferase DOT1L alleviates renal fibrosis through inhibition of renal fibroblast activation and epithelial-mesenchymal transition. FASEB J 2019;33:11941-11958. doi: https://doi.org/10.1096/fj.201801861R.

    Article  CAS  PubMed  Google Scholar 

  22. Helzlsouer KJ, Erlinger TP, Platz EA. C-reactive protein levels and subsequent cancer outcomes: results from a prospective cohort study. Eur J Cancer 2006;42:704-707.

    Article  CAS  Google Scholar 

  23. Shimetani N, Shimetani K, Mori M. Clinical evaluation of the measurement of serum procalcitonin: comparative study of procalcitonin and serum amyloid A protein in patients with high and low concentrations of serum C-reactive protein. Scand J Clin Lab Invest 2004;64:469-474.

    Article  CAS  Google Scholar 

  24. Saltzman RL, Peterson PK. Immunodeficiency of the elderly. Rev Infect Dis 1987; 9:1127-1139.

    Article  CAS  Google Scholar 

  25. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010;140:883- 899.

    Article  CAS  Google Scholar 

  26. Linton PJ, Dorshkind K. Age-related changes in lymphocyte development and function. Nat Immunol 2004;5:133-139.

    Article  CAS  Google Scholar 

  27. Kawakami K, Kadota J, Iida K, Shirai R, Abe K, Kohno S. Reduced immune function and malnutrition in the elderly. Tohoku J Exp Med 1999;187:157-171.

    Article  CAS  Google Scholar 

  28. Kimbara S, Kondo S. Immune checkpoint and inflammation as therapeutic targets in pancreatic carcinoma. World J Gastroenterol 2016;22:7440-7452. doi:https://doi.org/10.3748/wjg.v22.i33.7440.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Huang L, Liu S, Lei Y, Wang K, Xu M, Chen Y, Fu Q, Zhang P, Qin K, Cai Y, Fu S, Ge S, Yuan X. Systemic immune-inflammation index, thymidine phosphorylase and survival of localized gastric cancer patients after curative resection. Oncotarget 2016;7:44185-44193. doi: https://doi.org/10.18632/oncotarget.9923.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Lin JX, Wang ZK, Huang YQ, Xie JW, Wang JB, Lu J, Chen QY, Lin M, Tu RH, Huang ZN, Lin JL, Zheng CH, Huang CM, Li P. Dynamic changes in pre- and postoperative levels of inflammatory markers and their effects on the prognosis of patients with gastric cancer. J Gastrointest Surg 2020. doi: https://doi.org/10.1007/s11605-020-04523-8.

  31. Sun Y, Huang Z, Chi P. An inflammation index-based prediction of treatment response to neoadjuvant chemoradiotherapy for rectal mucinous adenocarcinoma. Int J Clin Oncol 2020. doi: https://doi.org/10.1007/s10147-020-01670-5.

  32. Wang D, Hu X, Xiao L, Long G, Yao L, Wang Z, Zhou LD. Prognostic nutritional index and systemic immune-inflammation index predict the prognosis of patients with HCC. J Gastrointest Surg 2020. doi: https://doi.org/10.1007/s11605-019-04492-7.

  33. Hua X, Deng JP, Long ZQ, Zhang WW, Huang X, Wen W, Guo L, He ZY, Lin HX. Prognostic significance of the skeletal muscle index and an inflammation biomarker in patients with breast cancer who underwent postoperative adjuvant radiotherapy. Curr Probl Cancer 2019;1:100513. doi: https://doi.org/10.1016/j.currproblcancer.2019.100513.

    Article  Google Scholar 

  34. Nishihira T, Hirayama K, Akimoto M, Sato S, Shineha R, Tan M, Kasai M. Significance of active nutritional support for maintenance of immunopotentiation on the surgical treatment of esophageal cancer. Nihon Geka Gakkai Zassi 1985;86:1104-1107.

    CAS  Google Scholar 

  35. Shirai R, Kadota J, Iida K, Kawakami K, Abe K, Yoshinaga M, Iwashita T, Matsubara Y, Oka M, Kohno S. Immunological competence and nutritional status in patients with lung cancer. Lung 1998;176:363-370.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Digestive and General Surgery, Faculty of Medicine, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan

    Noriyuki Hirahara, Yoshitsugu Tajima, Takeshi Matsubara, Yusuke Fujii, Shunsuke Kaji, Yasunari Kawabata, Ryoji Hyakudomi, Tetsu Yamamoto, Yuki Uchida & Takahito Taniura

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  1. Noriyuki Hirahara
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  2. Yoshitsugu Tajima
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  3. Takeshi Matsubara
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Contributions

NH was the lead author, and conceived this study. TM, YK, YF, SK, TY, RH, YU, and TT collected data, performed analysis, and drafted the manuscript. YT reviewed paper and technique of surgery. All authors read and approved the final manuscript.

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Correspondence to Noriyuki Hirahara.

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Hirahara, N., Tajima, Y., Matsubara, T. et al. Systemic Immune-Inflammation Index Predicts Overall Survival in Patients with Gastric Cancer: a Propensity Score–Matched Analysis. J Gastrointest Surg 25, 1124–1133 (2021). https://doi.org/10.1007/s11605-020-04710-7

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