Tumor-Associated Neutrophils as a New Prognostic Factor in Cancer: A Systematic Review and Meta-Analysis

<div><p>Purpose</p><p>Tumor-associated neutrophils (TAN) have been reported in a variety of malignancies. We conducted an up-to-date meta-analysis to evaluate the prognostic role of TAN in cancer.</p><p>Method</p><p>Pubmed, Embase and web of science databases were searched for studies published up to April 2013. Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated. The impact of neutrophils localization and primary antibody were also assessed.</p><p>Results</p><p>A total of 3946 patients with various solid tumors from 20 studies were included. High density of intratumoral neutrophils were independently associated with unfavorable survival; the pooled HRs were 1.68 (95%CI: 1.36–2.07, I² = 55.8%, <i>p</i><0.001) for recurrence-free survival (RFS)/disease-free survival (DFS), 3.36 (95%CI: 2.08–5.42, I² = 0%, <i>p</i><0.001) for cancer-specific survival (CSS) and 1.66 (95%CI: 1.37–2.01, I² = 70.5%, <i>p</i><0.001) for overall survival (OS). Peritumoral and stromal neutrophils were not statistically significantly associated with survival. When grouped by primary antibody, the pooled HRs were 1.80 (95%CI: 1.47–2.22, I² = 67.7%, <i>p</i><0.001) for CD66b, and 1.44 (95%CI: 0.90–2.30, I² = 45.9%, <i>p</i> = 0.125) for CD15, suggesting that CD66b positive TAN might have a better prognostic value than CD15.</p><p>Conclusion</p><p>High levels of intratumoral neutrophils are associated with unfavorable recurrence-free, cancer-specific and overall survival.</p></div

Characteristics of patients receiving chemotherapeutic regimens according to RRM1 expression.

<p>*Based on Fisher’s exact test.</p>#<p>Based on Student’s <i>t</i>-test.</p

Kaplan–Meier curves for non-small-cell lung cancer (NSCLC).

<p>A: Kaplan–Meier curve of OS for NSCLC; B: Kaplan–Meier curve of DFS for NSCLC.</p

Evaluation of Preoperative Hematologic Markers as Prognostic Factors and Establishment of Novel Risk Stratification in Resected pN0 Non-Small-Cell Lung Cancer

<div><p>Background</p><p>The aims of this study were to investigate whether the preoperative hematologic markers, the neutrophil-lymphocyte ratio (NLR) or the platelet-lymphocyte ratio (PLR) were prognostic indicators and to develop a novel risk stratification model in pN0 non-small-cell lung cancer (NSCLC).</p><p>Methods</p><p>We performed a retrospective analysis of 400 consecutive pN0 NSCLC patients. Prognostic values were evaluated by Cox proportional hazard model analyses and patients were stratified according to relative risks for patients’ survival.</p><p>Results</p><p>During the follow-up, 117 patients had cancer recurrence, and 86 patients died. In univariate analysis, age, gender, smoke status and tumor size as well as WBC, NEU, LYM, PLR and NLR were significantly associated with patients’ prognosis. In multivariate analysis, age, tumor size and NLR were independent predictors for patients’ overall survival (P = 0.024, 0.001, and 0.002 respectively). PLR didn’t associated with patients’ survival in multivariate analysis. Patients were stratified into 3 risk groups and the differences among the groups were significant according to disease free survival and overall survival (P = 0.000 and 0.000 respectively).</p><p>Conclusions</p><p>We confirmed that NLR other than PLR was an independent prognostic factor. Combination of NLR, age and tumor size could stratify pN0 NSCLC patients into 3 risk groups and enabled us to develop a novel risk stratification model.</p></div

Basic characteristics of NSCLC patients.

<p>Basic characteristics of NSCLC patients.</p

Sensitivity analysis of subgroups.

<p>(A) Sensitivity analysis of studies evaluated intratumoral neutrophils expression on OS. (B) Sensitivity analysis of studies evaluated intratumoral neutrophils expression on RFS/DFS.</p

Follow diagram of the meta-analysis.

<p>Follow diagram of the meta-analysis.</p

The Kaplan-Meier survival curve of NSCLC patients who underwent radical resection (n = 572).

<p>It is analyzed using Kaplan-Meier survival model, including 108 cases with blood calcium <2.2, and 464 cases with 2.2< = calcium< = 2.6. Log-rank comparisons revealed that blood calcium decrease(<2.2 µM) was associated with shorter survival (Log-rank; χ² = 26.172, <i>P</i><0.001).</p

Kaplan-Meier estimates according to low, intermediate and high risk groups on DFS (a) and OS (b).

<p>Kaplan-Meier estimates according to low, intermediate and high risk groups on DFS (a) and OS (b).</p

Survival analyses of inflammatory biomarkers and clinicopatholigic factors.

<p>Abbreviations: HR, hazard ratio; CI, confidence interval; TNM, tumour node metastasis; OS, overall survival; DFS, disease-free survival.</p><p>*, Not in the final step of multivariate analysis.</p><p>Survival analyses of inflammatory biomarkers and clinicopatholigic factors.</p