Prognostic value of lymphocyte monocyte ratio changes in patients with locally advanced gastric cancer: a single center retrospective cohort study_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HE Qichen , WANG Keshen , WANG Tao , LI Zhigang , GAN Shiying , ZHOU Huinian , YU Zeyuan ,  JIAO Zuoyi

Department of General Surgery, Lanzhou University Second Hospital, Lanzhou 730030, P. R. China;

Corresponding author：

JIAO Zuoyi, Email: jiaozy@lzu.edu.cn

Keywords：

locally advanced gastric cancer; lymphocyte-to-monocyte ratio; adjuvant therapy

DOI：

10.7507/1007-9424.202211076

Video：

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Objective To evaluate prognostic value of change of immune status in locally advanced gastric cancer (LAGC) patients. Methods We retrospective collected 210 LAGC patients who underwent treatment in our department from January 2013 to December 2018, then we collected lymphocyte-to-monocyte ratio (LMR) and cLMR (change of lymphocyte-to-monocyte ratio, cLMR) before operation and after three cycles of adjuvant chemotherapy. We had developed a new immune state change score (ICS) based on preoperative LMR (pLMR) and cLMR, and explored its prognostic value. The definition of ICS in this study was: ICS=1, pLMR≤4.53 and cLMR≤1; ICS=2, pLMR≤4.53 and cLMR>1, or pLMR>4.53 and cLMR≤1; ICS=3, pLMR>4.53 and cLMR>1. Results The results of multivariate Cox proportional hazard regression model showed that ICS was an influencing factor for overall survival [ICS=2, RR=0.397, 95%CI (0.260, 0.608), P<0.001; ICS=3, RR=0.080, 95%CI (0.040, 0.162), P<0.001), patients with ICS scores of 2 and 3 had better overall survival. In addition, the prognostic accuracy of ICS was superior to pLMR and Clmr, and the C-index of ICS [0.806, 95%CI (0.746, 0.865)] was higher than that of pLMR [0.717, 95%CI (0.635, 0.799), P=0.003)] and cLMR [0.723, 95%CI (0.641, 0.806), P=0.005)]. Based on this, a Nomogram model included ICS, CEA, and pTNM staging was constructed to predict the 3-year and 5-year survival rates of patients. The calibration curve and C-index [0.821, 95%CI (0.783, 0.859)] showed high discrimination and accuracy of Nomogram, and decision curve analysis confirmed that the model had good clinical application value. Conclusions The dynamic changes in the patient’s immune status before and after adjuvant therapy are related to the overall survival of LAGC patients. As an evaluating system which combined the cLMR and pLMR, ICS can better predict the prognosis of LAGC patients.

Citation： HE Qichen, WANG Keshen, WANG Tao, LI Zhigang, GAN Shiying, ZHOU Huinian, YU Zeyuan, JIAO Zuoyi. Prognostic value of lymphocyte monocyte ratio changes in patients with locally advanced gastric cancer: a single center retrospective cohort study. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(5): 561-568. doi: 10.7507/1007-9424.202211076 Copy

1.	Karimi P, Islami F, Anandasabapathy S, et al. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev, 2014, 23(5): 700-713.
2.	Wang W, Li YF, Sun XW, et al. Prognosis of 980 patients with gastric cancer after surgical resection. Chin J Cancer, 2010, 29(11): 923-930.
3.	Lim JB, Chung HW. Serum ENA78/CXCL5, SDF-1/CXCL12, and their combinations as potential biomarkers for prediction of the presence and distant metastasis of primary gastric cancer. Cytokine, 2015, 73(1): 16-22.
4.	Khalil DN, Smith EL, Brentjens RJ, et al. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol, 2016, 13(5): 273-290.
5.	Sasaki A, Nakamura Y, Mishima S, et al. Predictive factors for hyperprogressive disease during nivolumab as anti-PD1 treatment in patients with advanced gastric cancer. Gastric Cancer, 2019, 22(4): 793-802.
6.	Binder M, Rajkumar SV, Lacy MQ, et al. Peripheral blood biomarkers of early immune reconstitution in newly diagnosed multiple myeloma. Am J Hematol, 2019, 94(3): 306-311.
7.	Porrata LF, Ristow K, Colgan JP, et al. Peripheral blood lymphocyte/monocyte ratio at diagnosis and survival in classical Hodgkin’s lymphoma. Haematologica, 2012, 97(2): 262-269.
8.	Eo WK, Jeong DW, Chang HJ, et al. Absolute monocyte and lymphocyte count prognostic score for patients with gastric cancer. World J Gastroenterol, 2015, 21(9): 2668-2676.
9.	Goto W, Kashiwagi S, Asano Y, et al. Predictive value of lymphocyte-to-monocyte ratio in the preoperative setting for progression of patients with breast cancer. BMC Cancer, 2018, 18(1): 1137. doi: 10.1186/s12885-018-5051-9.
10.	Saito H, Kono Y, Murakami Y, et al. Prognostic significance of pre- and postoperative lymphocyte counts in patients with gastric cancer. Dig Surg, 2019, 36(2): 137-143.
11.	Feng F, Zheng G, Wang Q, et al. Low lymphocyte count and high monocyte count predicts poor prognosis of gastric cancer. BMC Gastroenterol, 2018, 18(1): 148. doi: 10.1186/s12876-018-0877-9.
12.	Ma JY, Liu Q. Clinicopathological and prognostic significance of lymphocyte to monocyte ratio in patients with gastric cancer: a meta-analysis. Int J Surg, 2018, 50: 67-71.
13.	Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer, 2011, 14(2): 113-123.
14.	Edge SB, American Joint Committee. American cancer, AJCC cancer staging handbook: from the AJCC cancer staging manual. 7th ed. New York: Springer, 2010: 718.
15.	Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res, 2004, 10(21): 7252-7259.
16.	Heagerty PJ, Lumley T, Pepe MS. Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics, 2000, 56(2): 337-344.
17.	Gu L, Li H, Chen L, et al. Prognostic role of lymphocyte to monocyte ratio for patients with cancer: evidence from a systematic review and meta-analysis. Oncotarget, 2016, 7(22): 31926-31942.
18.	Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity, 2004, 21(2): 137-148.
19.	赵阳, 程静. 手术前后中性粒细胞淋巴细胞比率变化对评估胃癌患者预后的临床价值. 中国普外基础与临床杂志, 2020, 27(12): 1538-1542.
20.	Azimi F, Scolyer RA, Rumcheva P, et al. Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma. J Clin Oncol, 2012, 30(21): 2678-2683.
21.	Augier S, Ciucci T, Luci C, et al. Inflammatory blood monocytes contribute to tumor development and represent a privileged target to improve host immunosurveillance. J Immunol, 2010, 185(12): 7165-7173.
22.	Galdiero MR, Bonavita E, Barajon I, et al. Tumor associated macrophages and neutrophils in cancer. Immunobiology, 2013, 218(11): 1402-1410.
23.	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(2): 403-412.
24.	Deng Q, He B, Liu X, et al. Prognostic value of pre-operative inflammatory response biomarkers in gastric cancer patients and the construction of a predictive model. J Transl Med, 2015, 13: 66. doi: 10.1186/s12967-015-0409-0.
25.	Fujiwara Y, Misawa T, Shiba H, et al. Postoperative peripheral absolute blood lymphocyte-to-monocyte ratio predicts therapeutic outcome after pancreatic resection in patients with pancreatic adenocarcinoma. Anticancer Res, 2014, 34(9): 5163-5168.
26.	Sekine K, Kanda S, Goto Y, et al. Change in the lymphocyte-to-monocyte ratio is an early surrogate marker of the efficacy of nivolumab monotherapy in advanced non-small-cell lung cancer. Lung Cancer, 2018, 124: 179-188.
27.	Galvez-Silva J, Maher OM, Park M, et al. Prognostic analysis of absolute lymphocyte and monocyte counts after autologous stem cell transplantation in children, adolescents, and young adults with refractory or relapsed hodgkin lymphoma. Biol Blood Marrow Transplant, 2017, 23(8): 1276-1281.
28.	Shariat SF, Karakiewicz PI, Suardi N, et al. Comparison of nomograms with other methods for predicting outcomes in prostate cancer: a critical analysis of the literature. Clin Cancer Res, 2008, 14(14): 4400-4407.
29.	Iasonos A, Schrag D, Raj GV, et al. How to build and interpret a nomogram for cancer prognosis. J Clin Oncol, 2008, 26(8): 1364-1370.

1. Karimi P, Islami F, Anandasabapathy S, et al. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev, 2014, 23(5): 700-713.
2. Wang W, Li YF, Sun XW, et al. Prognosis of 980 patients with gastric cancer after surgical resection. Chin J Cancer, 2010, 29(11): 923-930.
3. Lim JB, Chung HW. Serum ENA78/CXCL5, SDF-1/CXCL12, and their combinations as potential biomarkers for prediction of the presence and distant metastasis of primary gastric cancer. Cytokine, 2015, 73(1): 16-22.
4. Khalil DN, Smith EL, Brentjens RJ, et al. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol, 2016, 13(5): 273-290.
5. Sasaki A, Nakamura Y, Mishima S, et al. Predictive factors for hyperprogressive disease during nivolumab as anti-PD1 treatment in patients with advanced gastric cancer. Gastric Cancer, 2019, 22(4): 793-802.
6. Binder M, Rajkumar SV, Lacy MQ, et al. Peripheral blood biomarkers of early immune reconstitution in newly diagnosed multiple myeloma. Am J Hematol, 2019, 94(3): 306-311.
7. Porrata LF, Ristow K, Colgan JP, et al. Peripheral blood lymphocyte/monocyte ratio at diagnosis and survival in classical Hodgkin’s lymphoma. Haematologica, 2012, 97(2): 262-269.
8. Eo WK, Jeong DW, Chang HJ, et al. Absolute monocyte and lymphocyte count prognostic score for patients with gastric cancer. World J Gastroenterol, 2015, 21(9): 2668-2676.
9. Goto W, Kashiwagi S, Asano Y, et al. Predictive value of lymphocyte-to-monocyte ratio in the preoperative setting for progression of patients with breast cancer. BMC Cancer, 2018, 18(1): 1137. doi: 10.1186/s12885-018-5051-9.
10. Saito H, Kono Y, Murakami Y, et al. Prognostic significance of pre- and postoperative lymphocyte counts in patients with gastric cancer. Dig Surg, 2019, 36(2): 137-143.
11. Feng F, Zheng G, Wang Q, et al. Low lymphocyte count and high monocyte count predicts poor prognosis of gastric cancer. BMC Gastroenterol, 2018, 18(1): 148. doi: 10.1186/s12876-018-0877-9.
12. Ma JY, Liu Q. Clinicopathological and prognostic significance of lymphocyte to monocyte ratio in patients with gastric cancer: a meta-analysis. Int J Surg, 2018, 50: 67-71.
13. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer, 2011, 14(2): 113-123.
14. Edge SB, American Joint Committee. American cancer, AJCC cancer staging handbook: from the AJCC cancer staging manual. 7th ed. New York: Springer, 2010: 718.
15. Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res, 2004, 10(21): 7252-7259.
16. Heagerty PJ, Lumley T, Pepe MS. Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics, 2000, 56(2): 337-344.
17. Gu L, Li H, Chen L, et al. Prognostic role of lymphocyte to monocyte ratio for patients with cancer: evidence from a systematic review and meta-analysis. Oncotarget, 2016, 7(22): 31926-31942.
18. Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity, 2004, 21(2): 137-148.
19. 赵阳, 程静. 手术前后中性粒细胞淋巴细胞比率变化对评估胃癌患者预后的临床价值. 中国普外基础与临床杂志, 2020, 27(12): 1538-1542.
20. Azimi F, Scolyer RA, Rumcheva P, et al. Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma. J Clin Oncol, 2012, 30(21): 2678-2683.
21. Augier S, Ciucci T, Luci C, et al. Inflammatory blood monocytes contribute to tumor development and represent a privileged target to improve host immunosurveillance. J Immunol, 2010, 185(12): 7165-7173.
22. Galdiero MR, Bonavita E, Barajon I, et al. Tumor associated macrophages and neutrophils in cancer. Immunobiology, 2013, 218(11): 1402-1410.
23. 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(2): 403-412.
24. Deng Q, He B, Liu X, et al. Prognostic value of pre-operative inflammatory response biomarkers in gastric cancer patients and the construction of a predictive model. J Transl Med, 2015, 13: 66. doi: 10.1186/s12967-015-0409-0.
25. Fujiwara Y, Misawa T, Shiba H, et al. Postoperative peripheral absolute blood lymphocyte-to-monocyte ratio predicts therapeutic outcome after pancreatic resection in patients with pancreatic adenocarcinoma. Anticancer Res, 2014, 34(9): 5163-5168.
26. Sekine K, Kanda S, Goto Y, et al. Change in the lymphocyte-to-monocyte ratio is an early surrogate marker of the efficacy of nivolumab monotherapy in advanced non-small-cell lung cancer. Lung Cancer, 2018, 124: 179-188.
27. Galvez-Silva J, Maher OM, Park M, et al. Prognostic analysis of absolute lymphocyte and monocyte counts after autologous stem cell transplantation in children, adolescents, and young adults with refractory or relapsed hodgkin lymphoma. Biol Blood Marrow Transplant, 2017, 23(8): 1276-1281.
28. Shariat SF, Karakiewicz PI, Suardi N, et al. Comparison of nomograms with other methods for predicting outcomes in prostate cancer: a critical analysis of the literature. Clin Cancer Res, 2008, 14(14): 4400-4407.
29. Iasonos A, Schrag D, Raj GV, et al. How to build and interpret a nomogram for cancer prognosis. J Clin Oncol, 2008, 26(8): 1364-1370.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Prognostic value of lymphocyte monocyte ratio changes in patients with locally advanced gastric cancer: a single center retrospective cohort study

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