Predictive value of preoperative peripheral blood neutrophil percentage to serum albumin ratio for survival of patients with hepatocellular carcinoma after radical resection_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

XU Yueqing , LI Chuan ,  WEN Tianfu

Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

WEN Tianfu, Email: wentianfu@scu.edu.cn

Keywords：

neutrophil percentage-to-albumin ratio; hepatocellular carcinoma; prognosis

DOI：

10.7507/1007-9424.202411113

Video：

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Objective To investigate the predictive value of the preoperative peripheral blood neutrophil percentage-to-albumin ratio (NPAR) for survival after radical resection of hepatocellular carcinoma (HCC) and to construct a nomogram prediction model based on NPAR. Methods According to inclusion and exclusion criteria, the HCC patients with China Liver Cancer Staging (CNLC) stage Ⅰa–Ⅱa who underwent radical hepatectomy at West China Hospital of Sichuan University from January 2010 to December 2020 were retrospectively collected and then randomly divided into a training set and a validation set with a 7∶3 ratio. The optimal cutoff value for NPAR was determined using X-tile. Cox proportional hazards regression model was used to identify the independent risk factors for overall survival (OS) in HCC patients and then construct a nomogram model. The predictive performance of the model was evaluated using the C-index, receiver operating characteristic (ROC) curve, and calibration curve, as well as validated in the validation set. Results A total of 3 423 HCC patients with CNLC stage Ⅰa–Ⅱa were enrolled in this study, with 2 397 in the training set and 1 026 in the validation set. There were no statistically significant differences in baseline characteristics between the training and validation sets (P>0.05). The optimal cutoff value for NPAR was 17.0, and patients with NPAR ≤17.0 (2 124 cases) had significantly better OS and relapse-free survival (RFS) than those with NPAR>17.0 (273 cases). The multivariate Cox proportional hazards regression model analysis showed that the AFP>400 μg/L, NPAR>17.0, multiple tumors, tumor diameter >5 cm, poor tumor differentiation, capsular invasion, microvascular invasion, and satellite lesions were the independent risk factors affecting postoperative OS in HCC patients (RR>1, P<0.05). The nomogram constructed based on these risk factors demonstrated good discriminations for OS and RFS (C-indexes of 0.708 and 0.709, respectively) and predictive performance in both the training and validation sets. Conclusions Preoperative high NPAR (>17.0) in HCC patients with CNLC Ⅰa–Ⅱa stages is associated with significantly worse OS compared to those with low NPAR (≤17.0). The nomogram prediction model based on NPAR can effectively predict postoperative survival.

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2.	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
3.	郝运, 李川, 文天夫, 等. 全球及中国的肝癌流行病学特征: 基于《2022全球癌症统计报告》解读. 中国普外基础与临床杂志, 2024, 31(7): 781-789.
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5.	Pinna AD, Yang T, Mazzaferro V, et al. Liver transplantation and hepatic resection can achieve cure for hepatocellular carcinoma. Ann Surg, 2018, 268(5): 868-875.
6.	Tabrizian P, Jibara G, Shrager B, et al. Recurrence of hepatocellular cancer after resection: patterns, treatments, and prognosis. Ann Surg, 2015, 261(5): 947-955.
7.	Jiang Y, Xu D, Song H, et al. Inflammation and nutrition-based biomarkers in the prognosis of oesophageal cancer: a systematic review and meta-analysis. BMJ Open, 2021, 11(9): e048324. doi: 10.1136/bmjopen-2020-048324.
8.	Tawfik B, Mokdad AA, Patel PM, et al. The neutrophil to albumin ratio as a predictor of pathological complete response in rectal cancer patients following neoadjuvant chemoradiation. Anticancer Drugs, 2016, 27(9): 879-883.
9.	Li R, Sun Z, Song S, et al. NARFIB: A novel prognostic score based on the neutrophil-to-albumin ratio and fibrinogen can predict the prognosis of gastrointestinal stromal tumors. Cancer Manag Res, 2020, 12: 11183-11190.
10.	Ferro M, Babă DF, de Cobelli O, et al. Neutrophil percentage-to-albumin ratio predicts mortality in bladder cancer patients treated with neoadjuvant chemotherapy followed by radical cystectomy. Future Sci OA, 2021, 7(7): FSO709. doi: 10.2144/fsoa-2021-0008.
11.	Feng C, Yu H, Lei H, et al. A prognostic model using the neutrophil-albumin ratio and PG-SGA to predict overall survival in advanced palliative lung cancer. BMC Palliat Care, 2022, 21(1): 81. doi: 10.1186/s12904-022-00972-x.
12.	Tingle SJ, Severs GR, Goodfellow M, et al. NARCA: A novel prognostic scoring system using neutrophil-albumin ratio and CA19-9 to predict overall survival in palliative pancreatic cancer. J Surg Oncol, 2018, 118(4): 680-686.
13.	Chan AWH, Zhong J, Berhane S, et al. Development of pre and post-operative models to predict early recurrence of hepatocellular carcinoma after surgical resection. J Hepatol, 2018, 69(6): 1284-1293.
14.	Wu JC, Huang YH, Chau GY, et al. Risk factors for early and late recurrence in hepatitis B-related hepatocellular carcinoma. J Hepatol, 2009, 51(5): 890-897.
15.	Imamura H, Matsuyama Y, Tanaka E, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol, 2003, 38(2): 200-207.
16.	Linye H, Zijing X, Xiaoyun Z, et al. Tenofovir versus entecavir on the prognosis of hepatitis B-related hepatocellular carcinoma after surgical resection: a randomised controlled trial. Int J Surg, 2023, 109(10): 3032-3041.
17.	中华人民共和国国家卫生健康委员会. 原发性肝癌诊疗指南(2024年版). 肿瘤综合治疗电子杂志, 2024, 10(3): 17-68.
18.	Shen J, He L, Li C, et al. Prognostic nomograms for patients with resectable hepatocelluar carcinoma incorporating systemic inflammation and tumor characteristics. Oncotarget, 2016, 7(49): 80783-80793.
19.	Hu X, Xiang F, Feng Y, et al. Neutrophils promote tumor progression in oral squamous cell carcinoma by regulating EMT and JAK2/STAT3 signaling through chemerin. Front Oncol, 2022, 12: 812044. doi: 10.3389/fonc.2022.812044.
20.	Mano Y, Shirabe K, Yamashita Y, et al. Preoperative neutrophil-to-lymphocyte ratio is a predictor of survival after hepatectomy for hepatocellular carcinoma: a retrospective analysis. Ann Surg, 2013, 258(2): 301-305.
21.	Motomura T, Shirabe K, Mano Y, et al. Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment. J Hepatol, 2013, 58(1): 58-64.
22.	Itoh S, Yugawa K, Shimokawa M, et al. Prognostic significance of inflammatory biomarkers in hepatocellular carcinoma following hepatic resection. BJS Open, 2019, 3(4): 500-508.
23.	Mantovani A, Allavena P, Sica A, et al. Cancer-related inflammation. Nature, 2008, 454(7203): 436-444.
24.	Diakos CI, Charles KA, McMillan DC, et al. Cancer-related inflammation and treatment effectiveness. Lancet Oncol, 2014, 15(11): e493-e503. doi: 10.1016/S1470-2045(14)70263-3.
25.	Taniguchi K, Karin M. NF-κB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol, 2018, 18(5): 309-324.
26.	Singel KL, Segal BH. Neutrophils in the tumor microenvironment: trying to heal the wound that cannot heal. Immunol Rev, 2016, 273(1): 329-343.
27.	Nojiri S, Joh T. Albumin suppresses human hepatocellular carcinoma proliferation and the cell cycle. Int J Mol Sci, 2014, 15(3): 5163-5174.
28.	Bağırsakçı E, Şahin E, Atabey N, et al. Role of albumin in growth inhibition in hepatocellular carcinoma. Oncology, 2017, 93(2): 136-142.
29.	Carr BI, Guerra V. Serum albumin levels in relation to tumor parameters in hepatocellular carcinoma patients. Int J Biol Markers, 2017, 32(4): e391-e396. doi: 10.5301/ijbm.5000300.
30.	Bao X, Liu F, Lin J, et al. Nutritional assessment and prognosis of oral cancer patients: a large-scale prospective study. BMC Cancer, 2020, 20(1): 146. doi: 10.1186/s12885-020-6604-2.
31.	Dupont PJ, Warrens AN. Fas ligand exerts its pro-inflammatory effects via neutrophil recruitment but not activation. Immunology, 2007, 120(1): 133-139.
32.	CSCO肿瘤营养治疗专家委员会. 恶性肿瘤患者的营养治疗专家共识. 临床肿瘤学杂志, 2012, 17(1): 59-73.
33.	Hou J, Karin M, Sun B. Targeting cancer-promoting inflammation - have anti-inflammatory therapies come of age?. Nat Rev Clin Oncol, 2021, 18(5): 261-279.
34.	Behrens LM, van Egmond M, van den Berg TK. Neutrophils as immune effector cells in antibody therapy in cancer. Immunol Rev, 2023, 314(1): 280-301.

1. Zhou M, Wang H, Zeng X, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet, 2019, 394(10204): 1145-1158.
2. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
3. 郝运, 李川, 文天夫, 等. 全球及中国的肝癌流行病学特征: 基于《2022全球癌症统计报告》解读. 中国普外基础与临床杂志, 2024, 31(7): 781-789.
4. 姚一菲, 孙可欣, 郑荣寿. 《2022全球癌症统计报告》解读: 中国与全球对比. 中国普外基础与临床杂志, 2024, 31(7): 769-780.
5. Pinna AD, Yang T, Mazzaferro V, et al. Liver transplantation and hepatic resection can achieve cure for hepatocellular carcinoma. Ann Surg, 2018, 268(5): 868-875.
6. Tabrizian P, Jibara G, Shrager B, et al. Recurrence of hepatocellular cancer after resection: patterns, treatments, and prognosis. Ann Surg, 2015, 261(5): 947-955.
7. Jiang Y, Xu D, Song H, et al. Inflammation and nutrition-based biomarkers in the prognosis of oesophageal cancer: a systematic review and meta-analysis. BMJ Open, 2021, 11(9): e048324. doi: 10.1136/bmjopen-2020-048324.
8. Tawfik B, Mokdad AA, Patel PM, et al. The neutrophil to albumin ratio as a predictor of pathological complete response in rectal cancer patients following neoadjuvant chemoradiation. Anticancer Drugs, 2016, 27(9): 879-883.
9. Li R, Sun Z, Song S, et al. NARFIB: A novel prognostic score based on the neutrophil-to-albumin ratio and fibrinogen can predict the prognosis of gastrointestinal stromal tumors. Cancer Manag Res, 2020, 12: 11183-11190.
10. Ferro M, Babă DF, de Cobelli O, et al. Neutrophil percentage-to-albumin ratio predicts mortality in bladder cancer patients treated with neoadjuvant chemotherapy followed by radical cystectomy. Future Sci OA, 2021, 7(7): FSO709. doi: 10.2144/fsoa-2021-0008.
11. Feng C, Yu H, Lei H, et al. A prognostic model using the neutrophil-albumin ratio and PG-SGA to predict overall survival in advanced palliative lung cancer. BMC Palliat Care, 2022, 21(1): 81. doi: 10.1186/s12904-022-00972-x.
12. Tingle SJ, Severs GR, Goodfellow M, et al. NARCA: A novel prognostic scoring system using neutrophil-albumin ratio and CA19-9 to predict overall survival in palliative pancreatic cancer. J Surg Oncol, 2018, 118(4): 680-686.
13. Chan AWH, Zhong J, Berhane S, et al. Development of pre and post-operative models to predict early recurrence of hepatocellular carcinoma after surgical resection. J Hepatol, 2018, 69(6): 1284-1293.
14. Wu JC, Huang YH, Chau GY, et al. Risk factors for early and late recurrence in hepatitis B-related hepatocellular carcinoma. J Hepatol, 2009, 51(5): 890-897.
15. Imamura H, Matsuyama Y, Tanaka E, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol, 2003, 38(2): 200-207.
16. Linye H, Zijing X, Xiaoyun Z, et al. Tenofovir versus entecavir on the prognosis of hepatitis B-related hepatocellular carcinoma after surgical resection: a randomised controlled trial. Int J Surg, 2023, 109(10): 3032-3041.
17. 中华人民共和国国家卫生健康委员会. 原发性肝癌诊疗指南(2024年版). 肿瘤综合治疗电子杂志, 2024, 10(3): 17-68.
18. Shen J, He L, Li C, et al. Prognostic nomograms for patients with resectable hepatocelluar carcinoma incorporating systemic inflammation and tumor characteristics. Oncotarget, 2016, 7(49): 80783-80793.
19. Hu X, Xiang F, Feng Y, et al. Neutrophils promote tumor progression in oral squamous cell carcinoma by regulating EMT and JAK2/STAT3 signaling through chemerin. Front Oncol, 2022, 12: 812044. doi: 10.3389/fonc.2022.812044.
20. Mano Y, Shirabe K, Yamashita Y, et al. Preoperative neutrophil-to-lymphocyte ratio is a predictor of survival after hepatectomy for hepatocellular carcinoma: a retrospective analysis. Ann Surg, 2013, 258(2): 301-305.
21. Motomura T, Shirabe K, Mano Y, et al. Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment. J Hepatol, 2013, 58(1): 58-64.
22. Itoh S, Yugawa K, Shimokawa M, et al. Prognostic significance of inflammatory biomarkers in hepatocellular carcinoma following hepatic resection. BJS Open, 2019, 3(4): 500-508.
23. Mantovani A, Allavena P, Sica A, et al. Cancer-related inflammation. Nature, 2008, 454(7203): 436-444.
24. Diakos CI, Charles KA, McMillan DC, et al. Cancer-related inflammation and treatment effectiveness. Lancet Oncol, 2014, 15(11): e493-e503. doi: 10.1016/S1470-2045(14)70263-3.
25. Taniguchi K, Karin M. NF-κB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol, 2018, 18(5): 309-324.
26. Singel KL, Segal BH. Neutrophils in the tumor microenvironment: trying to heal the wound that cannot heal. Immunol Rev, 2016, 273(1): 329-343.
27. Nojiri S, Joh T. Albumin suppresses human hepatocellular carcinoma proliferation and the cell cycle. Int J Mol Sci, 2014, 15(3): 5163-5174.
28. Bağırsakçı E, Şahin E, Atabey N, et al. Role of albumin in growth inhibition in hepatocellular carcinoma. Oncology, 2017, 93(2): 136-142.
29. Carr BI, Guerra V. Serum albumin levels in relation to tumor parameters in hepatocellular carcinoma patients. Int J Biol Markers, 2017, 32(4): e391-e396. doi: 10.5301/ijbm.5000300.
30. Bao X, Liu F, Lin J, et al. Nutritional assessment and prognosis of oral cancer patients: a large-scale prospective study. BMC Cancer, 2020, 20(1): 146. doi: 10.1186/s12885-020-6604-2.
31. Dupont PJ, Warrens AN. Fas ligand exerts its pro-inflammatory effects via neutrophil recruitment but not activation. Immunology, 2007, 120(1): 133-139.
32. CSCO肿瘤营养治疗专家委员会. 恶性肿瘤患者的营养治疗专家共识. 临床肿瘤学杂志, 2012, 17(1): 59-73.
33. Hou J, Karin M, Sun B. Targeting cancer-promoting inflammation - have anti-inflammatory therapies come of age?. Nat Rev Clin Oncol, 2021, 18(5): 261-279.
34. Behrens LM, van Egmond M, van den Berg TK. Neutrophils as immune effector cells in antibody therapy in cancer. Immunol Rev, 2023, 314(1): 280-301.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Latest ArticlesPredictive value of preoperative peripheral blood neutrophil percentage to serum albumin ratio for survival of patients with hepatocellular carcinoma after radical resection

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