Correlation between preoperative peripheral blood NLR, PLR, SII and clinicopathological characteristics and prognosis of 101 patients with gastrointestinal stromal tumor_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

KANG Zhengyu ^1,2 , PENG Zhenwei ^1,2 , LI Ling ^2,3 , HU Xiaoyu ^2,3 , YANG Wensheng ^1,2 , NIE Huwei ^1,2 , CHEN Ailing ^2,3 ,  ZHANG Lin ^1,2,3

1. School of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, P. R. China;
2. Gastrointestinal Ward, Center of General Surgery, General Hospital of Western Theater Command of The Chinese People’s Liberation Army, Chengdu 610083, P. R. China;
3. School of Clinical Medicine, Southwest Jiaotong University, Chengdu 610031, P. R. China;

Corresponding author：

ZHANG Lin, Email: flysky8026@aliyun.com

Keywords：

gastrointestinal stromal tumor; neutrophil to lymphocyte ratio; platelet to lymphocyte ratio; systemic immune inflammation index; clinicopathological characteristics; recurrence-free survival

DOI：

10.7507/1007-9424.202108042

Video：

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Objective To investigate the correlation between the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune inflammation index (SII) and clinicopathological characteristics and prognosis in patients with gastrointestinal stromal tumor (GIST). Methods The clinicopathological data and blood routine results of 101 patients with GIST who were treated surgically in the General Hospital Western Theater Command PLA from December 2014 to December 2018 were collected retrospectively, samples were obtained to calculate NLR, PLR and SII. The optimal cutoff value of NLR, PLR and SII were evaluated by receiver operating characteristic (ROC) curve. The Chi-square test and t-test were used to analyze the relationship between NLR, PLR, SII and clinicopathological characteristics of GIST. The Kaplan-Meier plots and the log-rank test were used to analyze the influence factors affecting the recurrence-free survival (RFS) of patients with GIST. Multivariate Cox regression analyses was used to identify the independent influence factors affecting the RFS of patients with GIST. Results The preoperative peripheral blood NLR, PLR and SII of patients with GIST were correlated with the tumor site, tumor diameter and modified NIH risk stratification (P<0.05), but not with the mitotic count of tumor cells (P>0.05). Kaplan-Meier plots and log-rank test showed that NLR, PLR, SII, surgical method, tumor site, tumor diameter, mitosis rate and modified NIH risk stratification were the influential factors of RFS in with GIST. The multivariate Cox regression analysis revealed that postoperative whether to accept regular imatinib adjuvant therapy (HR=32.876, P<0.001), modified NIH risk stratification (HR=129.182, P<0.001), and PLR (HR=5.719, P=0.028) were independent influence factors affecting the RFS of patients with GIST. Conclusions Preoperative peripheral blood PLR, NLR, and SII are correlated with clinicopathological characteristics such as the tumor location, tumor diameter and modified NIH risk stratification, and are the influencing factors of postoperative RFS in patients with GIST. PLR is an independent predictor of RFS in patients with GIST.

Citation： KANG Zhengyu, PENG Zhenwei, LI Ling, HU Xiaoyu, YANG Wensheng, NIE Huwei, CHEN Ailing, ZHANG Lin. Correlation between preoperative peripheral blood NLR, PLR, SII and clinicopathological characteristics and prognosis of 101 patients with gastrointestinal stromal tumor. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(6): 731-737. doi: 10.7507/1007-9424.202108042 Copy

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2.	Poveda A, García Del Muro X, López-Guerrero JA, et al. GEIS guidelines for gastrointestinal sarcomas (GIST). Cancer Treat Rev, 2017, 55: 107-119.
3.	Kane WJ, Friel CM. Diagnosis and treatment of rectal gastrointestinal stromal tumors. Dis Colon Rectum, 2019, 62(5): 537-540.
4.	Corless CL, Barnett CM, Heinrich MC. Gastrointestinal stromal tumours: origin and molecular oncology. Nat Rev Cancer, 2011, 11(12): 865-878.
5.	Medeiros F, Corless CL, Duensing A, et al. KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications. Am J Surg Pathol, 2004, 28(7): 889-894.
6.	中国临床肿瘤学会指南工作委员会. 中国临床肿瘤学会(CSCO)胃肠间质瘤诊疗指南2020. 北京: 人民卫生出版社, 2020.
7.	Sanford DE, Belt BA, Panni RZ, et al. Inflammatory monocyte mobilization decreases patient survival in pancreatic cancer: a role for targeting the CCL2/CCR2 axis. Clin Cancer Res, 2013, 19(13): 3404-3415.
8.	Pribluda A, Elyada E, Wiener Z, et al. A senescence-inflammatory switch from cancer-inhibitory to cancer-promoting mechanism. Cancer Cell, 2013, 24(2): 242-256.
9.	Kumarasamy C, Sabarimurugan S, Madurantakam RM, et al. Prognostic significance of blood inflammatory biomarkers NLR, PLR, and LMR in cancer-A protocol for systematic review and meta-analysis. Medicine (Baltimore), 2019, 98(24): e14834. doi: 10.1097/MD.0000000000014834.
10.	Dupré A, Malik HZ. Inflammation and cancer: What a surgical oncologist should know. Eur J Surg Oncol, 2018, 44(5): 566-570.
11.	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(43): 75381-75388.
12.	李素琴, 李夏, 朱晓芸, 等. 四种术式治疗胃肠道间质瘤的临床对比研究. 胃肠病学和肝病学杂志, 2019, 28(4): 400-404.
13.	何天湖, 汤旭东, 龙庆林, 等. 内镜和腹腔镜及开腹手术治疗胃间质瘤的临床疗效. 中华消化外科杂志, 2018, 17(8): 843-847.
14.	李勇, 安昭杰, 檀碧波, 等. 胃肠间质瘤耐药的研究现状与进展. 世界华人消化杂志, 2020, 28(20): 999-1003.
15.	冯园园. 伊马替尼联合腹腔镜手术治疗胃肠间质瘤的临床效果及对预后的影响. 药品评价, 2020, 17(12): 45-47.
16.	Singel KL, Segal BH. Neutrophils in the tumor microenvironment: trying to heal the wound that cannot heal. Immunol Rev, 2016, 273(1): 329-343.
17.	Giese MA, Hind LE, Huttenlocher A. Neutrophil plasticity in the tumor microenvironment. Blood, 2019, 133(20): 2159-2167.
18.	Ostroumov D, Fekete-Drimusz N, Saborowski M, et al. CD4 and CD8 T lymphocyte interplay in controlling tumor growth. Cell Mol Life Sci, 2018, 75(4): 689-713.
19.	Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat Rev Immunol, 2020, 20(11): 651-668.
20.	Mlecnik B, Tosolini M, Kirilovsky A, et al. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol, 2011, 29(6): 610-618.
21.	Haemmerle M, Stone RL, Menter DG, et al. The platelet lifeline to cancer: challenges and opportunities. Cancer Cell, 2018, 33(6): 965-983.
22.	Goel HL, Mercurio AM. VEGF targets the tumour cell. Nat Rev Cancer, 2013, 13(12): 871-882.
23.	Schlesinger M. Role of platelets and platelet receptors in cancer metastasis. J Hematol Oncol, 2018, 11(1): 125.
24.	Itatani Y, Kawada K, Yamamoto T, et al. Resistance to anti-angiogenic therapy in cancer-alterations to anti-VEGF Pathway. Int J Mol Sci, 2018, 19(4): 1232.
25.	Apte RS, Chen DS, Ferrara N. VEGF in signaling and disease: beyond discovery and development. Cell, 2019, 176(6): 1248-1264.
26.	Sun Y, Zhang L. The clinical use of pretreatment NLR, PLR, and LMR in patients with esophageal squamous cell carcinoma: evidence from a meta-analysis. Cancer Manag Res, 2018, 10: 6167-6179.
27.	Wang L, Wang C, Wang J, et al. 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(10): 2077-2086.
28.	Zhang X, Zhao W, Yu Y, et al. Clinicopathological and prognostic significance of platelet-lymphocyte ratio (PLR) in gastric cancer: an updated meta-analysis. World J Surg Oncol, 2020, 18(1): 191.
29.	Kim MR, Kim AS, Choi HI, et al. Inflammatory markers for predicting overall survival in gastric cancer patients: A systematic review and meta-analysis. PLoS One, 2020, 15(7): e0236445.
30.	Qiu Y, Zhang Z, Chen Y. Prognostic value of pretreatment systemic immune-inflammation index in gastric cancer: A meta-analysis. Front Oncol, 2021, 11: 537140.
31.	Wang D, Bai N, Hu X, et al. Preoperative inflammatory markers of NLR and PLR as indicators of poor prognosis in resectable HCC. PeerJ, 2019, 7: e7132.
32.	Wang B, Huang Y, Lin T. Prognostic impact of elevated pre-treatment systemic immune-inflammation index (SII) in hepatocellular carcinoma: A meta-analysis. Medicine (Baltimore), 2020, 99(1): e18571.
33.	Zhang J, Zhang HY, Li J, et al. The elevated NLR, PLR and PLT may predict the prognosis of patients with colorectal cancer: a systematic review and meta-analysis. Oncotarget, 2017, 8(40): 68837-68846.
34.	Yatabe S, Eto K, Haruki K, et al. Signification of systemic immune-inflammation index for prediction of prognosis after resecting in patients with colorectal cancer. Int J Colorectal Dis, 2020, 35(8): 1549-1555.
35.	Diem S, Schmid S, Krapf M, et al. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic markers in patients with non-small cell lung cancer (NSCLC) treated with nivolumab. Lung Cancer, 2017, 111: 176-181.
36.	Alifano M. Systemic immune-inflammation index and prognosis of advanced non-small cell lung cancer. Ann Transl Med, 2020, 8(11): 667. doi: 10.21037/atm.2020.03.174.
37.	Zhu Y, Si W, Sun Q, et al. Platelet-lymphocyte ratio acts as an indicator of poor prognosis in patients with breast cancer. Oncotarget, 2017, 8(1): 1023-1030.
38.	Duan J, Pan L, Yang M. Preoperative elevated neutrophil-to-lymphocyte ratio (NLR) and derived NLR are associated with poor prognosis in patients with breast cancer: A meta-analysis. Medicine (Baltimore), 2018, 97(49): e13340. doi: 10.1097/MD.0000000000013340.
39.	Hua X, Long ZQ, Zhang YL, et al. Prognostic value of preoperative systemic immune-inflammation index in breast cancer: a propensity score-matching study. Front Oncol, 2020, 10: 580. doi: 10.3389/fonc.2020.00580.
40.	张道通, 李泽伦, 黄亮, 等. 胃肠道间质瘤三种术后复发风险评估标准及列线图的临床对比研究. 中国临床新医学, 2019, 12(11): 1163-1167.
41.	沈琳, 曹晖, 秦叔逵, 等. 中国胃肠间质瘤诊断治疗共识(2017年版). 肿瘤综合治疗电子杂志, 2018, 4(1): 31-43.
42.	方仕旭, 林彬, 王峰, 等. 胃间质瘤临床病理特征及预后分析. 中国医药导报, 2019, 16(20): 125-128.
43.	黄湘辉, 裘科跃, 袁旦平, 等. 102例胃肠间质瘤外科手术疗效及预后影响因素分析. 解放军医学院学报, 2019, 40(7): 655-659.

1. Søreide K, Sandvik OM, Søreide JA, et al. Global epidemiology of gastrointestinal stromal tumours (GIST): A systematic review of population-based cohort studies. Cancer Epidemiol, 2016, 40: 39-46.
2. Poveda A, García Del Muro X, López-Guerrero JA, et al. GEIS guidelines for gastrointestinal sarcomas (GIST). Cancer Treat Rev, 2017, 55: 107-119.
3. Kane WJ, Friel CM. Diagnosis and treatment of rectal gastrointestinal stromal tumors. Dis Colon Rectum, 2019, 62(5): 537-540.
4. Corless CL, Barnett CM, Heinrich MC. Gastrointestinal stromal tumours: origin and molecular oncology. Nat Rev Cancer, 2011, 11(12): 865-878.
5. Medeiros F, Corless CL, Duensing A, et al. KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications. Am J Surg Pathol, 2004, 28(7): 889-894.
6. 中国临床肿瘤学会指南工作委员会. 中国临床肿瘤学会(CSCO)胃肠间质瘤诊疗指南2020. 北京: 人民卫生出版社, 2020.
7. Sanford DE, Belt BA, Panni RZ, et al. Inflammatory monocyte mobilization decreases patient survival in pancreatic cancer: a role for targeting the CCL2/CCR2 axis. Clin Cancer Res, 2013, 19(13): 3404-3415.
8. Pribluda A, Elyada E, Wiener Z, et al. A senescence-inflammatory switch from cancer-inhibitory to cancer-promoting mechanism. Cancer Cell, 2013, 24(2): 242-256.
9. Kumarasamy C, Sabarimurugan S, Madurantakam RM, et al. Prognostic significance of blood inflammatory biomarkers NLR, PLR, and LMR in cancer-A protocol for systematic review and meta-analysis. Medicine (Baltimore), 2019, 98(24): e14834. doi: 10.1097/MD.0000000000014834.
10. Dupré A, Malik HZ. Inflammation and cancer: What a surgical oncologist should know. Eur J Surg Oncol, 2018, 44(5): 566-570.
11. 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(43): 75381-75388.
12. 李素琴, 李夏, 朱晓芸, 等. 四种术式治疗胃肠道间质瘤的临床对比研究. 胃肠病学和肝病学杂志, 2019, 28(4): 400-404.
13. 何天湖, 汤旭东, 龙庆林, 等. 内镜和腹腔镜及开腹手术治疗胃间质瘤的临床疗效. 中华消化外科杂志, 2018, 17(8): 843-847.
14. 李勇, 安昭杰, 檀碧波, 等. 胃肠间质瘤耐药的研究现状与进展. 世界华人消化杂志, 2020, 28(20): 999-1003.
15. 冯园园. 伊马替尼联合腹腔镜手术治疗胃肠间质瘤的临床效果及对预后的影响. 药品评价, 2020, 17(12): 45-47.
16. Singel KL, Segal BH. Neutrophils in the tumor microenvironment: trying to heal the wound that cannot heal. Immunol Rev, 2016, 273(1): 329-343.
17. Giese MA, Hind LE, Huttenlocher A. Neutrophil plasticity in the tumor microenvironment. Blood, 2019, 133(20): 2159-2167.
18. Ostroumov D, Fekete-Drimusz N, Saborowski M, et al. CD4 and CD8 T lymphocyte interplay in controlling tumor growth. Cell Mol Life Sci, 2018, 75(4): 689-713.
19. Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat Rev Immunol, 2020, 20(11): 651-668.
20. Mlecnik B, Tosolini M, Kirilovsky A, et al. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol, 2011, 29(6): 610-618.
21. Haemmerle M, Stone RL, Menter DG, et al. The platelet lifeline to cancer: challenges and opportunities. Cancer Cell, 2018, 33(6): 965-983.
22. Goel HL, Mercurio AM. VEGF targets the tumour cell. Nat Rev Cancer, 2013, 13(12): 871-882.
23. Schlesinger M. Role of platelets and platelet receptors in cancer metastasis. J Hematol Oncol, 2018, 11(1): 125.
24. Itatani Y, Kawada K, Yamamoto T, et al. Resistance to anti-angiogenic therapy in cancer-alterations to anti-VEGF Pathway. Int J Mol Sci, 2018, 19(4): 1232.
25. Apte RS, Chen DS, Ferrara N. VEGF in signaling and disease: beyond discovery and development. Cell, 2019, 176(6): 1248-1264.
26. Sun Y, Zhang L. The clinical use of pretreatment NLR, PLR, and LMR in patients with esophageal squamous cell carcinoma: evidence from a meta-analysis. Cancer Manag Res, 2018, 10: 6167-6179.
27. Wang L, Wang C, Wang J, et al. 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(10): 2077-2086.
28. Zhang X, Zhao W, Yu Y, et al. Clinicopathological and prognostic significance of platelet-lymphocyte ratio (PLR) in gastric cancer: an updated meta-analysis. World J Surg Oncol, 2020, 18(1): 191.
29. Kim MR, Kim AS, Choi HI, et al. Inflammatory markers for predicting overall survival in gastric cancer patients: A systematic review and meta-analysis. PLoS One, 2020, 15(7): e0236445.
30. Qiu Y, Zhang Z, Chen Y. Prognostic value of pretreatment systemic immune-inflammation index in gastric cancer: A meta-analysis. Front Oncol, 2021, 11: 537140.
31. Wang D, Bai N, Hu X, et al. Preoperative inflammatory markers of NLR and PLR as indicators of poor prognosis in resectable HCC. PeerJ, 2019, 7: e7132.
32. Wang B, Huang Y, Lin T. Prognostic impact of elevated pre-treatment systemic immune-inflammation index (SII) in hepatocellular carcinoma: A meta-analysis. Medicine (Baltimore), 2020, 99(1): e18571.
33. Zhang J, Zhang HY, Li J, et al. The elevated NLR, PLR and PLT may predict the prognosis of patients with colorectal cancer: a systematic review and meta-analysis. Oncotarget, 2017, 8(40): 68837-68846.
34. Yatabe S, Eto K, Haruki K, et al. Signification of systemic immune-inflammation index for prediction of prognosis after resecting in patients with colorectal cancer. Int J Colorectal Dis, 2020, 35(8): 1549-1555.
35. Diem S, Schmid S, Krapf M, et al. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic markers in patients with non-small cell lung cancer (NSCLC) treated with nivolumab. Lung Cancer, 2017, 111: 176-181.
36. Alifano M. Systemic immune-inflammation index and prognosis of advanced non-small cell lung cancer. Ann Transl Med, 2020, 8(11): 667. doi: 10.21037/atm.2020.03.174.
37. Zhu Y, Si W, Sun Q, et al. Platelet-lymphocyte ratio acts as an indicator of poor prognosis in patients with breast cancer. Oncotarget, 2017, 8(1): 1023-1030.
38. Duan J, Pan L, Yang M. Preoperative elevated neutrophil-to-lymphocyte ratio (NLR) and derived NLR are associated with poor prognosis in patients with breast cancer: A meta-analysis. Medicine (Baltimore), 2018, 97(49): e13340. doi: 10.1097/MD.0000000000013340.
39. Hua X, Long ZQ, Zhang YL, et al. Prognostic value of preoperative systemic immune-inflammation index in breast cancer: a propensity score-matching study. Front Oncol, 2020, 10: 580. doi: 10.3389/fonc.2020.00580.
40. 张道通, 李泽伦, 黄亮, 等. 胃肠道间质瘤三种术后复发风险评估标准及列线图的临床对比研究. 中国临床新医学, 2019, 12(11): 1163-1167.
41. 沈琳, 曹晖, 秦叔逵, 等. 中国胃肠间质瘤诊断治疗共识(2017年版). 肿瘤综合治疗电子杂志, 2018, 4(1): 31-43.
42. 方仕旭, 林彬, 王峰, 等. 胃间质瘤临床病理特征及预后分析. 中国医药导报, 2019, 16(20): 125-128.
43. 黄湘辉, 裘科跃, 袁旦平, 等. 102例胃肠间质瘤外科手术疗效及预后影响因素分析. 解放军医学院学报, 2019, 40(7): 655-659.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Correlation between preoperative peripheral blood NLR, PLR, SII and clinicopathological characteristics and prognosis of 101 patients with gastrointestinal stromal tumor

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