Predictive Value of Pan-immune-inflammation Value for Prognosis of Patients with Resectable Colorectal Cancer
-
摘要:目的
探讨泛免疫炎症值（PIV）与可切除结直肠癌患者预后的相关性并建立相关的预测模型。
方法纳入753例接受原发病灶切除术且病理学诊断为结直肠癌的患者。将其随机分为训练（n=527）和测试（n=226）队列。通过时间依赖性受试者操作特征（ROC）曲线确定PIV的最佳截断值，将患者分为高水平组和低水平组，分析PIV高、低水平组与患者临床病理特征及生存情况之间的关系。卡方检验、Kaplan-Meier生存分析和Cox回归分析来评估预后。C指数和Brier评分评估模型的准确性。
结果在总生存期（OS）的单变量模型中，高（> 231）基线PIV（HR=1.627; 95%CI: 1.155~2.292, P=0.005）提示PIV水平可能是OS的独立预后因素。依据PIV绘制的诺模图C指数为0.823。其校准曲线显示1年和3年OS率的预测和观察结果之间具有良好的一致性，OS的Brier评分分别为0.035和0.068。
结论PIV可作为可切除结直肠癌患者预后的依据，我们成功建立了一个指导结直肠癌患者临床决策的新型预后模型。
Abstract:ObjectiveTo explore the correlation of the pan-immune-inflammation value (PIV) and the prognosis of patients with resectable colorectal cancer (CRC) and establish a predictive model.
MethodsA total of 753 patients who underwent primary lesion resection and were pathologically diagnosed with CRC were enrolled. They were randomly divided into training (n=527) and test (n=226) cohorts. The best cutoff value of PIV was determined by the time-dependent receiver operator characteristics curve, and patients were divided into high- and low-level groups to analyze the relationship between the high- and low-level groups of PIV and the clinicopathological characteristics and survival of patients. Chi-square test, Kaplan-Meier survival analysis, and Cox regression analysis were used to evaluate the prognosis. The accuracy of the model was evaluated by C index and Brier score.
ResultsIn the univariate model of overall survival (OS), high (> 231) baseline PIV (HR=1.627; 95%CI: 1.155-2.292, P=0.005) suggested that PIV level might be an independent prognostic factor for OS. The nomogram plotted according to PIV had a C index of 0.823. Its calibration curve showed good agreement between predicted and observed outcomes for one- and three-year OS probabilities, with Brier score of 0.035 and 0.068 for OS, respectively.
ConclusionPIV can be used as a prognostic marker in patients with resectable CRC, and a novel prognostic model to guide clinical decision-making in CRC is successfully established.
-
Key words:
- Colorectal cancer /
- Pan-immune-inflammation value /
- Prognosis /
- Nomogram
-
Competing interests: The authors declare that they have no competing interests.利益冲突声明：所有作者均声明不存在利益冲突。作者贡献：梁 鑫：设计方案、统计数据及撰写文章梁新军：指导设计方向及论文修改魏少忠：设计方案、提出论文修改指导性建议
-
![]()
图 1 预测训练队列中的OS率的时间依赖性ROC曲线(A)、A U C曲线图(B)、一年(C)及三年(D)校准曲线
Figure 1 Time-dependent ROC curve(A), time AUC(B), one-year (C) and three-year(D) calibration curve for predicting OS rate in the training cohort
![]()
图 3 预测测试队列中的O S率的时间依赖性ROC曲线(A)、AUC曲线图(B)、一年(C)及三年(D)校准曲线
Figure 3 Time-dependent ROC curve(A), time AUC(B), one-year (C) and three-year(D) calibration curve for predicting OS rate in the test cohort
![]()
图 4 结直肠癌根治术后患者PIV生存曲线图
Figure 4 PIV survival curves of patients after radical resection of colorectal cancer
表 1 结直肠癌患者的人口学和肿瘤特征
Table 1 Demographic and tumor characteristics of patients with colorectal cancer
下载: 导出CSV
表 2 Cox比例风险模型对影响结直肠癌患者总生存率因素的单因素和多因素分析
Table 2 Univariate and multivariate analyses of the factors affecting colorectal cancer patients's OS by Cox proportional hazard model
下载: 导出CSV
-
[1] Siegel RL, Miller KD, Fuchs HE, et al. Cancer Statistics, 2021[J]. CA Cancer J Clin, 2021, 71(1): 7-33. doi: 10.3322/caac.21654
[2] Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(3): 145-164. doi: 10.3322/caac.21601
[3] Aggarwal BB, Vijayalekshmi RV, Sung B. Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe[J]. Clin Cancer Res, 2009, 15(2): 425-430. doi: 10.1158/1078-0432.CCR-08-0149
[4] Alifano M, Mansuet-Lupo A, Lococo F, et al. Systemic inflammation, nutritional status and tumor immune microenvironment determine outcome of resected non-small cell lung cancer[J]. PLoS One, 2014, 9(9): e106914. doi: 10.1371/journal.pone.0106914
[5] Shrihari TG. Dual role of inflammatory mediators in cancer[J]. Ecancermedicalscience, 2017, 11: 721.
[6] Mantovani A, Marchesi F, Malesci A, et al. Tumour-associated macrophages as treatment targets in oncology[J]. Nat Rev Clin Oncol, 2017, 14(7): 399-416. doi: 10.1038/nrclinonc.2016.217
[7] Mazaki J, Katsumata K, Kasahara K, et al. Neutrophil-to-lymphocyte ratio is a prognostic factor for colon cancer: a propensity score analysis[J]. BMC Cancer, 2020, 20(1): 922. doi: 10.1186/s12885-020-07429-5
[8] Chen JH, Zhai ET, Yuan YJ, et al. Systemic immune-inflammation index for predicting prognosis of colorectal cancer[J]. World J Gastroenterol, 2017, 23(34): 6261-6272. doi: 10.3748/wjg.v23.i34.6261
[9] Edin S, Wikberg ML, Dahlin AM, et al. The distribution of macrophages with a M1 or M2 phenotype in relation to prognosis and the molecular characteristics of colorectal cancer[J]. PLoS One, 2012, 7(10): e47045. doi: 10.1371/journal.pone.0047045
[10] Fucà G, Beninato T, Bini M, et al. The Pan-Immune-Inflammation Value in Patients with Metastatic Melanoma Receiving First-Line Therapy[J]. Target Oncol, 2021, 16(4): 529-536. doi: 10.1007/s11523-021-00819-0
[11] Zeng R, Liu F, Fang C, et al. PIV and PILE Score at Baseline Predict Clinical Outcome of Anti-PD-1/PD-L1 Inhibitor Combined With Chemotherapy in Extensive-Stage Small Cell Lung Cancer Patients[J]. Front Immunol, 2021, 12: 724443. doi: 10.3389/fimmu.2021.724443
[12] Sahin AB, Cubukcu E, Ocak B, et al. Low pan-immune-inflammation-value predicts better chemotherapy response and survival in breast cancer patients treated with neoadjuvant chemotherapy[J]. Sci Rep, 2021, 11(1): 14662. doi: 10.1038/s41598-021-94184-7
[13] Ligorio F, Fucà G, Zattarin E, et al. The Pan-Immune-Inflammation-Value Predicts the Survival of Patients with Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Breast Cancer Treated with First-Line Taxane-Trastuzumab-Pertuzumab[J]. Cancers (Basel), 2021, 13(8): 1964. doi: 10.3390/cancers13081964
[14] Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing[J]. N Engl J Med, 1986, 315(26): 1650-1659. doi: 10.1056/NEJM198612253152606
[15] Giese MA, Hind LE, Huttenlocher A. Neutrophil plasticity in the tumor microenvironment[J]. Blood, 2019, 133(20): 2159-2167. doi: 10.1182/blood-2018-11-844548
[16] Powell DR, Huttenlocher A. Neutrophils in the Tumor Microenvironment[J]. Trends Immunol, 2016, 37(1): 41-52. doi: 10.1016/j.it.2015.11.008
[17] Zhang X, Zhang W, Yuan X, et al. Neutrophils in cancer development and progression: Roles, mechanisms, and implications (Review)[J]. Int J Oncol, 2016, 49(3): 857-867. doi: 10.3892/ijo.2016.3616
[18] Rosenberg SA, Spiess P, Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes[J]. Science, 1986, 233(4770): 1318-1321. doi: 10.1126/science.3489291
[19] Paijens ST, Vledder A, de Bruyn M, et al. Tumor-infiltrating lymphocytes in the immunotherapy era[J]. Cell Mol Immunol, 2021, 18(4): 842-859. doi: 10.1038/s41423-020-00565-9
[20] Nieswandt B, Hafner M, Echtenacher B, et al. Lysis of tumor cells by natural killer cells in mice is impeded by platelets[J]. Cancer Res, 1999, 59(6): 1295-1300. http://pdfs.semanticscholar.org/c955/12465e6e7a6ba95355969d91ff14a15e1cd5.pdf
[21] Schlesinger M. Role of platelets and platelet receptors in cancer metastasis[J]. J Hematol Oncol, 2018, 11(1): 125. doi: 10.1186/s13045-018-0669-2
[22] Ugel S, Canè S, De Sanctis F, et al. Monocytes in the Tumor Microenvironment[J]. Annu Rev Pathol, 2021, 16: 93-122. doi: 10.1146/annurev-pathmechdis-012418-013058
[23] Kim R, Hashimoto A, Markosyan N, et al. Ferroptosis of tumour neutrophils causes immune suppression in cancer[J]. Nature, 2022, 612(7939): 338-346. doi: 10.1038/s41586-022-05443-0
[24] Veglia F, Sanseviero E, Gabrilovich DI. Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity[J]. Nat Rev Immunol, 2021, 21(8): 485-498. doi: 10.1038/s41577-020-00490-y
[25] 韩晶, 王贵英, 张难, 等. 肿瘤部位及临床病理特征对不同TNM分期行结直肠癌根治性切除术患者预后的影响研究[J]. 中国全科医学, 2020, 23(18): 2275-2283. https://www.cnki.com.cn/Article/CJFDTOTAL-QKYX202018010.htm Han J, Wang GY, Zhang N, et al. Associations of Primary Tumor Site and Clinicopathologic Features with TNM-related Survival in Patients with Radical Resection of Colorectal Cancer[J]. Zhongguo Quan Ke Yi Xue, 2020, 23(18): 2275-2283. https://www.cnki.com.cn/Article/CJFDTOTAL-QKYX202018010.htm
[26] 李程, 闫柯, 霍斌亮, 等. 结直肠癌不同病理特征患者化疗前后循环肿瘤DNA水平变化及预后预测的列线图模型构建[J]. 疑难病杂志, 2022, 21(6): 566-570, 581. https://www.cnki.com.cn/Article/CJFDTOTAL-YNBZ202206003.htm Li C, Yan K, Huo BL, et al. Construction of a nomogram model for changes in circulating tumor DNA levels before and after chemotherapy in pa-tients with colorectal cancer with different pathological characteristics and prognosis prediction[J]. Yi Nan Bing Za Zhi, 2022, 21(6): 566-570, 581. https://www.cnki.com.cn/Article/CJFDTOTAL-YNBZ202206003.htm
[27] Fucà G, Guarini V, Antoniotti C, et al. The Pan-Immune-Inflammation Value Is a New Prognostic Biomarker in Metastatic Colorectal Cancer: Results From a Pooled-Analysis of the Valentino and TRIBE First-Line Trials[J]. Br J Cancer, 2020, 123(3): 403-409. doi: 10.1038/s41416-020-0894-7
[28] Corti F, Lonardi S, Intini R, et al. The Pan-Immune-Inflammation Value in microsatellite instability-high metastatic colorectal cancer patients treated with immune checkpoint inhibitors[J]. Eur J Cancer, 2021, 150: 155-167. doi: 10.1016/j.ejca.2021.03.043
计量
- 文章访问数: 1600
- HTML全文浏览量: 523
- PDF下载量: 590
