Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Front Immunol. 2018 Oct 12;9:2354. doi: 10.3389/fimmu.2018.02354. eCollection 2018.
We aimed to explore the prognostic value of blood leukocyte and to generate a predictive model to refine risk stratification for colorectal cancers. 6,558 patients with colorectal cancers were identified eligible respectively in Fudan University Shanghai Cancer Center (FUSCC) between May, 2008 and October, 2016. Then the entire set is divided into a training set and a testing set. The prognostic value of pretreatment white blood cell count and clinicopathologic parameters in the context of tumor-infiltrating lymphocytes (TIL) and neutrophils was investigated. Conventional leukocytosis (≥10,000/μl) was significantly associated with decreased overall survival (OS) and disease-free survival (DFS) ( < 0.05). In fact, moderately elevated leukocyte (≥7,500/μl) has also been identified as an independent prognostic factor for survivals in the training, testing, and entire sets, respectively. And leukocytosis correlated with advanced T-stage ( < 0.001), M-stage ( < 0.001), poor differentiation tumor ( = 0.023) and Glasgow prognostic score, even predicted for worse relapse postoperatively ( = 0.001) and resistance to chemotherapy. In addition, nomograms on OS and DFS were established according to leukocytosis and other significant factors, demonstrating a great prediction accuracy. Importantly, pretreatment leukocytosis had a significantly lower intra-tumor CD3+ and CD8+ TIL infiltration ( < 0.001 and = 0.033), whereas low CD3+ and CD8+ TIL expression in tumor were associated with worse OS and DFS ( = 0.02 and = 0.015). In conclusion, our study validates leukocytosis as an independent prognostic factor in colorectal cancers. Our data provide for the first-time vital insight on the correlation of peripheral pretreatment leukocytosis with the tumor-infiltrating cells contexture and might be relevant for future risk stratification.
我们旨在探讨血液白细胞的预后价值，并建立预测模型以细化结直肠癌的风险分层。我们分别在复旦大学附属肿瘤医院（FUSCC）于 2008 年 5 月至 2016 年 10 月期间筛选了 6558 名结直肠癌患者。然后，将整个数据集分为训练集和测试集。我们研究了肿瘤浸润淋巴细胞（TIL）和中性粒细胞背景下预处理白细胞计数和临床病理参数的预后价值。常规白细胞增多症（≥10,000/μl）与总生存期（OS）和无病生存期（DFS）降低显著相关（<0.05）。事实上，中等程度升高的白细胞（≥7,500/μl）也被确定为训练集、测试集和整个数据集生存的独立预后因素。白细胞增多症与晚期 T 期（<0.001）、M 期（<0.001）、分化不良肿瘤（=0.023）和格拉斯哥预后评分相关，甚至预测术后复发更差（=0.001）和对化疗的耐药性。此外，根据白细胞增多症和其他显著因素建立了 OS 和 DFS 的列线图，显示出很好的预测准确性。重要的是，预处理白细胞增多症与肿瘤内 CD3+和 CD8+TIL 浸润显著降低（<0.001 和=0.033），而肿瘤中低 CD3+和 CD8+TIL 表达与较差的 OS 和 DFS 相关（=0.02 和=0.015）。总之，我们的研究验证了白细胞增多症是结直肠癌的独立预后因素。我们的数据首次提供了外周预处理白细胞增多症与肿瘤浸润细胞结构之间相关性的重要见解，可能与未来的风险分层相关。
