Prognostic value of platelet-to-lymphocyte ratio in small cell lung cancer: a meta-analysis_West China Medical Journal

Authors：

WANG Jin ¹ , XU Li ¹ , WANG Yang ¹ , ZOU Linlin ¹ , LUO Dan ¹ ,  WANG Daoxin ²

1. Department of Respiratory and Critical Care Medicine, , the First People’s Hospital of Chongqing Liang Jiang New Area, Chongqing 401121, P. R. China;
2. Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P. R. China;

Corresponding author：

WANG Daoxin, Email: wangdaoxin1@163.com

Keywords：

Platelet-to-lymphocyte ratio; small cell lung cancer; prognosis; meta-analysis

DOI：

10.7507/1002-0179.202011274

Video：

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Objective To assess the prognostic value of platelet-to-lymphocyte ratio (PLR) in small cell lung cancer (SCLC). Methods We searched PubMed, OVID, Cochrane Library, Wanfang database, China National Knowledge Infrastructure, and CQVIP database to obtain relevant literature published up to January 2022. We screened the literature, extracted data and evaluated the quality according to the inclusion and exclusion criteria, and then performed a meta-analysis by using the hazard risk (HR) and 95% confidence interval (CI) to assess the prognostic value of PLR. Results A total of 4261 patients with SCLC were included in 15 eligible studies. The results showed that high pretreatment PLR was negatively associated with overall survival (OS) [HR=1.311, 95%CI (1.125, 1.527), P=0.001], but not with progression-free survival (PFS) [HR=1.112, 95%CI (0.966, 1.280), P=0.139]. Subgroup analyses showed that high PLR had prognostic value in patients with limited period and limited period + extensive phase SCLC [limited period: HR=1.556, 95%CI (1.327, 1.824), P<0.001; limited period + extensive phase: HR=1.245, 95%CI (1.043, 1.486), P=0.015]; when the cut-off value of PLR was less than 150, the result was significant for patients with SCLC [HR=1.420, 95%CI (1.235, 1.631), P<0.001]; regardless of race, PLR had prognostic value in SCLC patients [Caucasian: HR=1.528, 95%CI (1.181, 1.976), P<0.001; Asian: HR=1.283, 95%CI (1.085, 1.517), P=0.004]. Conclusions High pretreatment PLR may be related to the poor prognosis of SCLC, especially limited period SCLC. PLR could be a prognostic factor in SCLC, but more larger-sample studies are still needed to verify that.

Citation： WANG Jin, XU Li, WANG Yang, ZOU Linlin, LUO Dan, WANG Daoxin. Prognostic value of platelet-to-lymphocyte ratio in small cell lung cancer: a meta-analysis. West China Medical Journal, 2022, 37(1): 40-47. doi: 10.7507/1002-0179.202011274 Copy

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2.	DeSantis CE, Lin CC, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin, 2014, 64(4): 252-271.
3.	Li L, Li W, Chen N, et al. FLI1 exonic circular RNAs as a novel oncogenic driver to promote tumor metastasis in small cell lung cancer. Clin Cancer Res, 2019, 25(4): 1302-1317.
4.	Nisman B, Biran H, Ramu N, et al. The diagnostic and prognostic value of ProGRP in lung cancer. Anticancer Res, 2009, 29(11): 4827-4832.
5.	Salgia R, Weaver RW, McCleod M, et al. Prognostic and predictive value of circulating tumor cells and CXCR4 expression as biomarkers for a CXCR4 peptide antagonist in combination with carboplatin-etoposide in small cell lung cancer: exploratory analysis of a phase Ⅱ study. Invest New Drugs, 2017, 35(3): 334-344.
6.	Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell, 2010, 140(6): 883-899.
7.	Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science, 2011, 331(6024): 1565-1570.
8.	Wang F, Li P, Li FS. Prognostic role of C-reactive protein to albumin ratio in colorectal cancer: a meta analysis. Medicine, 2019, 98(29): e16064.
9.	Tuomisto AE, Mäkinen MJ, Väyrynen JP. Systemic inflammation in colorectal cancer: underlying factors, effects, and prognostic significance. World J Gastroenterol, 2019, 25(31): 4383-4404.
10.	Li B, Zhou P, Liu YJ, et al. Platelet-to-lymphocyte ratio in advanced cancer: review and meta-analysis. Clin Chim Acta, 2018, 483: 48-56.
11.	Wells GA, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Appl Eng Agric, 2014, 18(6): 727-734.
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15.	Hong X, Cui B, Wang M, et al. Systemic immune-inflammation index, based on platelet counts and neutrophil-lymphocyte ratio, is useful for predicting prognosis in small cell lung cancer. Tohoku J Exp Med, 2015, 236(4): 297-304.
16.	Kang MH, Go SI, Song HN, et al. The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with small-cell lung cancer. Br J Cancer, 2014, 111(3): 452-460.
17.	Liu D, Huang Y, Li L, et al. High neutrophil-to-lymphocyte ratios confer poor prognoses in patients with small cell lung cancer. BMC Cancer, 2017, 17(1): 882.
18.	Sakin A, Sahin S, Yasar N, et al. The relation between hemogram parameters and survival in extensive-stage small cell lung cancer. Oncol Res Treat, 2019, 42(10): 506-515.
19.	Suzuki R, Wei X, Allen PK, et al. Prognostic significance of total lymphocyte count, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio in limited-stage small-cell lung cancer. Clin Lung Cancer, 2019, 20(2): 117-123.
20.	Xie D, Marks R, Zhang MR, et al. Nomograms predict overall survival for patients with small-cell lung cancer incorporating pretreatment peripheral blood markers. J Thorac Oncol, 2015, 10(8): 1213-1220.
21.	Zhang Q, Qu Y, Liu H, et al. Initial platelet-to-lymphocyte count as prognostic factor in limited-stage small cell lung cancer. Biomark Med, 2019, 13(4): 249-258.
22.	Wu F, Yang S, Tang X, et al. Prognostic value of baseline hemoglobin-to-red blood cell distribution width ratio in small cell lung cancer: a retrospective analysis. Thorac Cancer, 2020, 11(4): 888-897.
23.	Shen XB, Wang Y, Shan BJ, et al. Prognostic significance of platelet-to-lymphocyte ratio (PLR) and mean platelet volume (MPV) during etoposide-based first-line treatment in small cell lung cancer patients. Cancer Manag Res, 2019, 11: 8965-8975.
24.	王立伟, 王键玮, 贾伟, 等. 血小板与淋巴细胞比值同小细胞肺癌临床预后的相关性分析. 肿瘤代谢与营养电子杂志, 2019, 6(2): 196-199.
25.	Deng M, Ma XE, 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(23): 37200-37207.
26.	王鑫, 支修益. 中性粒细胞/淋巴细胞比值和血小板/淋巴细胞比值对小细胞肺癌患者预后价值的相关研究. 中国医学前沿杂志(电子版), 2017, 9(5): 106-110.
27.	Lohinai Z, Bonanno L, Aksarin A, et al. Neutrophil-lymphocyte ratio is prognostic in early stage resected small-cell lung cancer. PeerJ, 2019, 7: e7232.
28.	Wang X, Teng F, Kong L, et al. Pretreatment neutrophil-to-lymphocyte ratio as a survival predictor for small-cell lung cancer. Onco Targets Ther, 2016, 9: 5761-5770.
29.	Chen CJ, Yang HT, Cai D, et al. Preoperative peripheral blood neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratio (PLR) related nomograms predict the survival of patients with limited-stage small-cell lung cancer. Transl Lung Cancer Res, 2021, 10(2): 866-877.
30.	Zhou X, Du Y, Huang Z, et al. Prognostic value of PLR in various cancers: a meta-analysis. PLoS One, 2014, 9(6): e101119.
31.	Templeton AJ, Ace O, McNamara MG, et al. Prognostic role of platelet to lymphocyte ratio in solid tumors: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev, 2014, 23(7): 1204-1212.
32.	Zhang H, Gao L, Zhang B, et al. Prognostic value of platelet to lymphocyte ratio in non-small cell lung cancer: a systematic review and meta-analysis. Sci Rep, 2016, 6: 22618.
33.	Qiang G, Liang C, Xiao F, et al. Prognostic significance of platelet-to-lymphocyte ratio in non-small-cell lung cancer: a meta-analysis. Onco Targets Ther, 2016, 9: 869-876.
34.	Ding N, Pang Z, Shen H, et al. The prognostic value of PLR in lung cancer, a meta-analysis based on results from a large consecutive cohort. Sci Rep, 2016, 6: 34823.
35.	Wojtukiewicz MZ, Sierko E, Hempel D, et al. Platelets and cancer angiogenesis nexus. Cancer Metastasis Rev, 2017, 36(2): 249-262.
36.	Raungkaewmanee S, Tangjitgamol S, Manusirivithaya S, et al. Platelet to lymphocyte ratio as a prognostic factor for epithelial ovarian cancer. J Gynecol Oncol, 2012, 23(4): 265-273.
37.	Bremnes RM, Busund LT, Kilvær TL, et al. The role of tumor-infiltrating lymphocytes in development, progression, and prognosis of non-small cell lung cancer. J Thorac Oncol, 2016, 11(6): 789-800.
38.	Man YG, Stojadinovic A, Mason J, et al. Tumor-infiltrating immune cells promoting tumor invasion and metastasis: existing theories. J Cancer, 2013, 4(1): 84-95.
39.	Lissoni P, Brivio F, Fumagalli L, et al. Efficacy of cancer chemotherapy in relation to the pretreatment number of lymphocytes in patients with metastatic solid tumors. Int J Biol Markers, 2004, 19(2): 135-140.
40.	Kawai O, Ishii G, Kubota K, et al. Predominant infiltration of macrophages and CD8⁺ T Cells in cancer nests is a significant predictor of survival in stage Ⅳ nonsmall cell lung cancer. Cancer, 2008, 113(6): 1387-1395.

1. Travis WD. The 2015 WHO classification of lung tumors. Pathologe, 2014, 35(Suppl 2): 188.
2. DeSantis CE, Lin CC, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin, 2014, 64(4): 252-271.
3. Li L, Li W, Chen N, et al. FLI1 exonic circular RNAs as a novel oncogenic driver to promote tumor metastasis in small cell lung cancer. Clin Cancer Res, 2019, 25(4): 1302-1317.
4. Nisman B, Biran H, Ramu N, et al. The diagnostic and prognostic value of ProGRP in lung cancer. Anticancer Res, 2009, 29(11): 4827-4832.
5. Salgia R, Weaver RW, McCleod M, et al. Prognostic and predictive value of circulating tumor cells and CXCR4 expression as biomarkers for a CXCR4 peptide antagonist in combination with carboplatin-etoposide in small cell lung cancer: exploratory analysis of a phase Ⅱ study. Invest New Drugs, 2017, 35(3): 334-344.
6. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell, 2010, 140(6): 883-899.
7. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science, 2011, 331(6024): 1565-1570.
8. Wang F, Li P, Li FS. Prognostic role of C-reactive protein to albumin ratio in colorectal cancer: a meta analysis. Medicine, 2019, 98(29): e16064.
9. Tuomisto AE, Mäkinen MJ, Väyrynen JP. Systemic inflammation in colorectal cancer: underlying factors, effects, and prognostic significance. World J Gastroenterol, 2019, 25(31): 4383-4404.
10. Li B, Zhou P, Liu YJ, et al. Platelet-to-lymphocyte ratio in advanced cancer: review and meta-analysis. Clin Chim Acta, 2018, 483: 48-56.
11. Wells GA, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Appl Eng Agric, 2014, 18(6): 727-734.
12. Tierney JF, Stewart LA, Ghersi D, et al. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials, 2007, 8: 16.
13. Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions version 5.1. 0 [updated March 2011]. The Cochrane Collaboration, 2011. http://www.cochrane-handbook.org.
14. Higgins JT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med, 2002, 21(11): 1539-1558.
15. Hong X, Cui B, Wang M, et al. Systemic immune-inflammation index, based on platelet counts and neutrophil-lymphocyte ratio, is useful for predicting prognosis in small cell lung cancer. Tohoku J Exp Med, 2015, 236(4): 297-304.
16. Kang MH, Go SI, Song HN, et al. The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with small-cell lung cancer. Br J Cancer, 2014, 111(3): 452-460.
17. Liu D, Huang Y, Li L, et al. High neutrophil-to-lymphocyte ratios confer poor prognoses in patients with small cell lung cancer. BMC Cancer, 2017, 17(1): 882.
18. Sakin A, Sahin S, Yasar N, et al. The relation between hemogram parameters and survival in extensive-stage small cell lung cancer. Oncol Res Treat, 2019, 42(10): 506-515.
19. Suzuki R, Wei X, Allen PK, et al. Prognostic significance of total lymphocyte count, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio in limited-stage small-cell lung cancer. Clin Lung Cancer, 2019, 20(2): 117-123.
20. Xie D, Marks R, Zhang MR, et al. Nomograms predict overall survival for patients with small-cell lung cancer incorporating pretreatment peripheral blood markers. J Thorac Oncol, 2015, 10(8): 1213-1220.
21. Zhang Q, Qu Y, Liu H, et al. Initial platelet-to-lymphocyte count as prognostic factor in limited-stage small cell lung cancer. Biomark Med, 2019, 13(4): 249-258.
22. Wu F, Yang S, Tang X, et al. Prognostic value of baseline hemoglobin-to-red blood cell distribution width ratio in small cell lung cancer: a retrospective analysis. Thorac Cancer, 2020, 11(4): 888-897.
23. Shen XB, Wang Y, Shan BJ, et al. Prognostic significance of platelet-to-lymphocyte ratio (PLR) and mean platelet volume (MPV) during etoposide-based first-line treatment in small cell lung cancer patients. Cancer Manag Res, 2019, 11: 8965-8975.
24. 王立伟, 王键玮, 贾伟, 等. 血小板与淋巴细胞比值同小细胞肺癌临床预后的相关性分析. 肿瘤代谢与营养电子杂志, 2019, 6(2): 196-199.
25. Deng M, Ma XE, 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(23): 37200-37207.
26. 王鑫, 支修益. 中性粒细胞/淋巴细胞比值和血小板/淋巴细胞比值对小细胞肺癌患者预后价值的相关研究. 中国医学前沿杂志(电子版), 2017, 9(5): 106-110.
27. Lohinai Z, Bonanno L, Aksarin A, et al. Neutrophil-lymphocyte ratio is prognostic in early stage resected small-cell lung cancer. PeerJ, 2019, 7: e7232.
28. Wang X, Teng F, Kong L, et al. Pretreatment neutrophil-to-lymphocyte ratio as a survival predictor for small-cell lung cancer. Onco Targets Ther, 2016, 9: 5761-5770.
29. Chen CJ, Yang HT, Cai D, et al. Preoperative peripheral blood neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratio (PLR) related nomograms predict the survival of patients with limited-stage small-cell lung cancer. Transl Lung Cancer Res, 2021, 10(2): 866-877.
30. Zhou X, Du Y, Huang Z, et al. Prognostic value of PLR in various cancers: a meta-analysis. PLoS One, 2014, 9(6): e101119.
31. Templeton AJ, Ace O, McNamara MG, et al. Prognostic role of platelet to lymphocyte ratio in solid tumors: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev, 2014, 23(7): 1204-1212.
32. Zhang H, Gao L, Zhang B, et al. Prognostic value of platelet to lymphocyte ratio in non-small cell lung cancer: a systematic review and meta-analysis. Sci Rep, 2016, 6: 22618.
33. Qiang G, Liang C, Xiao F, et al. Prognostic significance of platelet-to-lymphocyte ratio in non-small-cell lung cancer: a meta-analysis. Onco Targets Ther, 2016, 9: 869-876.
34. Ding N, Pang Z, Shen H, et al. The prognostic value of PLR in lung cancer, a meta-analysis based on results from a large consecutive cohort. Sci Rep, 2016, 6: 34823.
35. Wojtukiewicz MZ, Sierko E, Hempel D, et al. Platelets and cancer angiogenesis nexus. Cancer Metastasis Rev, 2017, 36(2): 249-262.
36. Raungkaewmanee S, Tangjitgamol S, Manusirivithaya S, et al. Platelet to lymphocyte ratio as a prognostic factor for epithelial ovarian cancer. J Gynecol Oncol, 2012, 23(4): 265-273.
37. Bremnes RM, Busund LT, Kilvær TL, et al. The role of tumor-infiltrating lymphocytes in development, progression, and prognosis of non-small cell lung cancer. J Thorac Oncol, 2016, 11(6): 789-800.
38. Man YG, Stojadinovic A, Mason J, et al. Tumor-infiltrating immune cells promoting tumor invasion and metastasis: existing theories. J Cancer, 2013, 4(1): 84-95.
39. Lissoni P, Brivio F, Fumagalli L, et al. Efficacy of cancer chemotherapy in relation to the pretreatment number of lymphocytes in patients with metastatic solid tumors. Int J Biol Markers, 2004, 19(2): 135-140.
40. Kawai O, Ishii G, Kubota K, et al. Predominant infiltration of macrophages and CD8⁺ T Cells in cancer nests is a significant predictor of survival in stage Ⅳ nonsmall cell lung cancer. Cancer, 2008, 113(6): 1387-1395.

West China Medical Journal

Prognostic value of platelet-to-lymphocyte ratio in small cell lung cancer: a meta-analysis

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