Prognostic Value of Combination of Inflammatory and Tumor Markers in Resectable Gastric Cancer

Abstract

Background

Inflammatory response and tumor marker levels have been shown to correlate with the prognosis in several human tumors. However, only a few studies on these markers have been performed in gastric cancer (GC) patients; the clinical significance of the combined markers is unclear. We aimed to evaluate the role of the combination of preoperative neutrophil-to-lymphocyte ratio (NLR) and carbohydrate antigen 19-9 (CA19-9) for predicting the prognosis of patients with GC.

Methods

This retrospective study included 458 patients who underwent gastrectomy with curative intent between January 2013 and July 2014 in the second hospital of Lanzhou University. Receiver operating characteristic curve (ROC) was performed to determine the cut-off values for biomarkers, and their prognostic values were assessed using the Kaplan-Meier curve. The combined score indicators were established based on the optimal cut-off values, which range from 0 to 2. Prognostic significances for overall survival (OS) were assessed by univariate and multivariate Cox regression analysis. Nomogram was used as a visual supplement for the prognostic score system, and the predictive accuracy and discriminative ability were determined by the concordance index (C-index) and calibration curve.

Results

The Kaplan-Meier survival analysis showed that the 1-, 3-, and 5-year OS were 66.2% (n = 303), 42.8% (n = 196), and 40.2% (n = 184) in all 458 patients, respectively. The high NLR (≥1.96), PLR (≥126), CA19-9 (≥27 U/mL), and CEA (≥ 5 ng/mL) were associated with poor prognosis of GC patients. The NLR + CA19-9 score indicator proved to be related to tumor size, lymph node metastasis, vascular invasion, perineural invasion, T stage, N stage, TNM stage, PLR, and CEA in patients with GC and an independent prognostic factor for prediction of 5-year OS (score 1: HR = 1.423, 95%CI: 1.049–1.929, P = 0.023; score 2: HR = 2.740, 95%CI: 1.882–3.990, P < 0.001). NLR + CA19-9 has a better predictive ability than other combined or single score indicators based on inflammation and tumor markers (AUC = 0.662, 95%CI: 0.616–0.705, P < 0.001). Moreover, a nomogram was established by the significant characteristics in the multivariate analysis for OS, which represented high accuracy (C-index = 0.692, 95%CI: 0.675–0.708).

Conclusion

NLR + CA19-9 can independently predict the overall survival of patients with gastric cancer after surgery. The prognostic nomogram based on NLR + CA19-9 is a convenient, economical, and effective prognostic system for clinical practice.

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References

  1. 1.

    Melina Arnold, Abnet Christian-C, Neale Rachel-E, et al. Global Burden of 5 Major Types Of Gastrointestinal Cancer[J]. Gastroenterology, 2020.

  2. 2.

    Bray F, J Ferlay, I Soerjomataram, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.[J]. CA: a cancer journal for clinicians, 2018, 68(6): 394-424.

  3. 3.

    Balakrishnan M, R George, A Sharma, et al. Changing Trends in Stomach Cancer Throughout the World.[J]. Current gastroenterology reports, 2017, 19(8): 36.

    Article  Google Scholar 

  4. 4.

    Hamilton TD, AL Mahar, B Haas, et al. The impact of advanced age on short-term outcomes following gastric cancer resection: an ACS-NSQIP analysis.[J]. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2018, 21(4): 710-719.

    CAS  Article  Google Scholar 

  5. 5.

    Daniel-R Rice, Farooq Ayesha, Hyer J-Madison, et al. Health expenditures and financial burden among patients with major gastrointestinal cancers relative to other common cancers in the United States[J]. Surgery, 2020, 167(7).

  6. 6.

    Kai Zhang, Yin Jian, Huang Huiyao, et al. Expenditure and Financial Burden for Stomach Cancer Diagnosis and Treatment in China: A Multicenter Study[J]. Frontiers in Public Health, 2020, 8.

  7. 7.

    Sergei-I Grivennikov, Greten Florian-R, Karin Michael. Immunity, Inflammation, and Cancer[J]. Cell, 2010, 140(6): 883-899.

    CAS  Article  Google Scholar 

  8. 8.

    Lee K, H Hwang, KT Nam. Immune response and the tumor microenvironment: how they communicate to regulate gastric cancer.[J]. Gut and liver, 2014, 8(2): 131-139.

    CAS  Article  Google Scholar 

  9. 9.

    Zhang X, D Hu, X Lin, et al. Prognostic Value of an Inflammation-Related Index in 6,865 Chinese Patients With Postoperative Digestive Tract Cancers: The FIESTA Study.[J]. Frontiers in oncology, 2019, 9427.

  10. 10.

    Yu-Chen, Pan, Zhi-Fang Jia, et al. Preoperative lymphocyte-to-monocyte ratio (LMR) could independently predict overall survival of resectable gastric cancer patients.[J]. Medicine, 2018, 97(52): e13896.

    Article  Google Scholar 

  11. 11.

    Feng LW, J Li, LF Liang, et al. A Predictive Scoring System Based on Inflammatory and Tumor Markers for Gastric Cancer Patients Undergoing Curative Resection.[J]. Cancer management and research, 2020, 123937-3948.

  12. 12.

    Song S, C Li, S Li, et al. Derived neutrophil to lymphocyte ratio and monocyte to lymphocyte ratio may be better biomarkers for predicting overall survival of patients with advanced gastric cancer.[J]. OncoTargets and therapy, 2017, 103145-3154.

  13. 13.

    Sturgeon CM, MJ Duffy, BR Hofmann, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in liver, bladder, cervical, and gastric cancers.[J]. Clinical chemistry, 2010, 56(6): e1-e48.

    CAS  Article  Google Scholar 

  14. 14.

    Wang W, SR Seeruttun, C Fang, et al. Prognostic Significance of Carcinoembryonic Antigen Staining in Cancer Tissues of Gastric Cancer Patients.[J]. Annals of surgical oncology, 2016, 23(4): 1244-1251.

    CAS  Article  Google Scholar 

  15. 15.

    Lin JX, W Wang, JP Lin, et al. Preoperative Tumor Markers Independently Predict Survival in Stage III Gastric Cancer Patients: Should We Include Tumor Markers in AJCC Staging?[J]. Annals of surgical oncology, 2018, 25(9): 2703-2712.

    Article  Google Scholar 

  16. 16.

    Fang X, J Wei, X He, et al. Landscape of dietary factors associated with risk of gastric cancer: A systematic review and dose-response meta-analysis of prospective cohort studies.[J]. European journal of cancer (Oxford, England : 1990), 2015, 51(18): 2820-2832.

    Article  Google Scholar 

  17. 17.

    Shinko D, CI Diakos, SJ Clarke, et al. Cancer-Related Systemic Inflammation: The Challenges and Therapeutic Opportunities for Personalized Medicine.[J]. Clinical pharmacology and therapeutics, 2017, 102(4): 599-610.

    Article  Google Scholar 

  18. 18.

    Botta C, V Barbieri, D Ciliberto, et al. Systemic inflammatory status at baseline predicts bevacizumab benefit in advanced non-small cell lung cancer patients[J]. Cancer Biology & Therapy, 2013, 14(6): 469-475.

    CAS  Article  Google Scholar 

  19. 19.

    Masucci MT, M Minopoli, MV Carriero. Tumor Associated Neutrophils. Their Role in Tumorigenesis, Metastasis, Prognosis and Therapy.[J]. Frontiers in oncology, 2019, 91146.

  20. 20.

    Quigley DA, V Kristensen. Predicting prognosis and therapeutic response from interactions between lymphocytes and tumor cells.[J]. Molecular oncology, 2015, 9(10): 2054-2062.

    CAS  Article  Google Scholar 

  21. 21.

    Kambara Y, H Miyake, H Nagai, et al. CA19-9 is a significant prognostic marker of patients with stage III gastric cancer.[J]. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 2020.

  22. 22.

    Zhang J, J Ruan, W Wang, et al. Prognostic Value of the Combination of CEA and Fibrinogen/Albumin Ratio in Resectable Gastric Cancer.[J]. Cancer management and research, 2020, 122767-2775.

  23. 23.

    Zhou C, X Zhong, Y Song, et al. Prognostic Biomarkers for Gastric Cancer: An Umbrella Review of the Evidence.[J]. Frontiers in oncology, 2019, 9:13-21.

    Article  Google Scholar 

  24. 24.

    Toyoda H, T Kumada, T Tada, et al. Prognostic significance of a combination of pre- and post-treatment tumor markers for hepatocellular carcinoma curatively treated with hepatectomy.[J]. Journal of hepatology, 2012, 57(6): 1251-1257.

    CAS  Article  Google Scholar 

  25. 25.

    Lin JP, JX Lin, YB Ma, et al. Prognostic significance of pre- and post-operative tumour markers for patients with gastric cancer.[J]. British journal of cancer, 2020.

  26. 26.

    Lin JX, LZ Lin, YH Tang, et al. Which Nutritional Scoring System Is More Suitable for Evaluating the Short- or Long-Term Prognosis of Patients with Gastric Cancer Who Underwent Radical Gastrectomy?[J]. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, 2020, 24(9): 1969-1977.

    Article  Google Scholar 

  27. 27.

    Pang W, N Lou, C Jin, et al. Combination of preoperative platelet/lymphocyte and neutrophil/lymphocyte rates and tumor-related factors to predict lymph node metastasis in patients with gastric cancer.[J]. European journal of gastroenterology & hepatology, 2016, 28(5): 493-502.

    CAS  Article  Google Scholar 

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Acknowledgements

The authors thank all the medical staff who contributed to the maintenance of the medical record database.

Funding

This study was supported by the Beijing Sisco Clinical Oncology Research Foundation (No. Y-HR2018-147) and the Cuiying Science And Technology Innovation Project of Lanzhou University (No. CY2018-BJ02).

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Liang Guo contributed to the conception and design of the work, analysis, interpretation of data, and manuscript drafting. Kang Chen and Hai-Peng Liu contributed to data collection and manuscript revision. Qi Wang contributed to the conception and design of the work, data analysis, and manuscript drafting. Xiao Chen was responsible for the design of research ideas and the accuracy of all aspects of the work.

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Correspondence to Xiao Chen.

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Guo, L., Wang, Q., Chen, K. et al. Prognostic Value of Combination of Inflammatory and Tumor Markers in Resectable Gastric Cancer. J Gastrointest Surg (2021). https://doi.org/10.1007/s11605-021-04944-z

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Keywords

  • Neutrophil-to-lymphocyte ratio
  • Carbohydrate antigen 19-9
  • Prognosis
  • Gastric cancer