Abstract
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) (p < 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 (p < 0.001), M-stage (p < 0.001), poor differentiation tumor (p = 0.023) and Glasgow prognostic score, even predicted for worse relapse postoperatively (p = 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 (p < 0.001 and p = 0.033), whereas low CD3+ and CD8+ TIL expression in tumor were associated with worse OS and DFS (p = 0.02 and p = 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.
Highlights
Growing evidences have emerged in recent years that inflammation may be the origin of many malignancies [1, 2]
Conventionally,pretreatment leukocytosis was defined as the detection of a leukocyte count over 10,000/μl
In order to assess the association of pretreatment leukocytosis and cancer prognosis, we performed Kaplan–Meier survival analysis and log-rank tests for the overall survival and disease-free survival
Summary
Growing evidences have emerged in recent years that inflammation may be the origin of many malignancies [1, 2]. The current prognostic model applied in clinical practice for risk stratification and treatment management mainly depends on tumor cell-centered stratification systems (TNM staging system), but even patients with the same stage can have very distinct prognosis [5] As this staging system narrowly concentrated on the tumor cells without incorporating the effects of the host inflammation and immune response. Being an inflammatory-associated tumor, colorectal cancer is characterized by infiltration of heterogeneous immune cells and peripheral hematologic profile disorder, which configure the complicated microenvironment affecting tumor development [6]. Prognostic serum marker such as, leukocyte counts, is easier to use in bedside, which are our focus and under investigation. We will provide insight on the clinical outcome of leukocytosis in correlation with microenvironment context
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