Weng Meilin, Zhao Wenling, Yue Ying, Guo Miaomiao, Nan Ke, Liao Qingwu, Sun Minli, Zhou Di, Miao Changhong
Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Anesthesiology, Shanghai Cancer Center, Fudan University, Shanghai, China.
Front Oncol. 2022 Jul 29;12:943423. doi: 10.3389/fonc.2022.943423. eCollection 2022.
The correlation between high white blood cell (WBC) count and poor prognosis has been identified in various types of cancer; however, the clinical significance and immune context of WBC count in colorectal cancer remains unclear.
Between February 2009 and November 2014, 7,433 patients at the Shanghai Cancer Center who had undergone elective surgery for colorectal cancer were enrolled in this retrospective cohort study. Patients were divided into two groups: low and high preoperative WBC groups. Propensity score matching was used to address the differences in baseline characteristics. The Kaplan-Meier method and Cox regression analysis were used to identify independent prognostic factors in colorectal cancer patients. Tumor-infiltrating immune cells in the high and low preoperative WBC groups were compared using immunohistochemical staining.
Of the 7,433 patients who underwent colorectal cancer surgery and were available for analysis, 5,750 were included in the low preoperative WBC group, and 1,683 were included in the high preoperative WBC group. After propensity score matching, 1,553 patients were included in each group. Kaplan-Meier survival curves showed that a high preoperative WBC count was associated with a decreased overall survival (P = 0.002) and disease-free survival (P = 0.003), and that preoperative WBC count was an independent risk factor for overall survival (hazard ratio, 1.234; 95% confidence interval, 1.068-1.426; P = 0.004) and disease-free survival (hazard ratio, 1.210; 95% confidence interval, 1.047-1.397, P = 0.01). Compared to the low preoperative WBC group, the high preoperative WBC group exhibited higher expression of regulatory T cells (P = 0.0034), CD68 macrophages (P = 0.0071), and CD66b neutrophils (P = 0.0041); increased expression of programmed cell death protein 1 (P = 0.005) and programmed cell death ligand 1 (P = 0.0019); and lower expression of CD8 T cells (P = 0.0057) in colorectal cancer patients.
Our research indicates that a high preoperative WBC count is a prognostic indicator in colorectal cancer patients and is associated with an immunosuppressive tumor microenvironment, which could aid in future risk stratification.
在各类癌症中均已发现高白细胞(WBC)计数与预后不良之间存在关联;然而,结直肠癌中WBC计数的临床意义及免疫背景仍不明确。
2009年2月至2014年11月期间,上海癌症中心7433例行择期结直肠癌手术的患者纳入本回顾性队列研究。患者分为两组:术前WBC计数低和高的组。采用倾向评分匹配法处理基线特征差异。使用Kaplan-Meier法和Cox回归分析确定结直肠癌患者的独立预后因素。通过免疫组化染色比较术前WBC计数高和低的组中的肿瘤浸润免疫细胞。
在7433例行结直肠癌手术且可进行分析的患者中,5750例纳入术前WBC计数低的组,1683例纳入术前WBC计数高的组。倾向评分匹配后,每组纳入1553例患者。Kaplan-Meier生存曲线显示,术前高WBC计数与总生存期降低(P = 0.002)和无病生存期降低(P = 0.003)相关,且术前WBC计数是总生存期(风险比,1.234;95%置信区间,1.068 - 1.426;P = 0.004)和无病生存期(风险比,1.210;95%置信区间,1.047 - 1.397,P = 0.01)的独立危险因素。与术前WBC计数低的组相比,术前WBC计数高的组在结直肠癌患者中表现出调节性T细胞(P = 0.0034)、CD68巨噬细胞(P = 0.0071)和CD66b中性粒细胞(P = 0.0041)的表达更高;程序性细胞死亡蛋白1(P = 0.005)和程序性细胞死亡配体1(P = 0.0019)的表达增加;以及CD8 T细胞的表达更低(P = 0.0057)。
我们的研究表明,术前高WBC计数是结直肠癌患者的预后指标,且与免疫抑制性肿瘤微环境相关,这可能有助于未来的风险分层。