We conducted a retrospective analysis of patients diagnosed with NSCLC who underwent surgery at the Tazuke Kofukai Medical Research Institute, Kitano Hospital, between January, 2007 and December, 2011. All the patients met the following criteria: pathological confirmation of NSCLC; complete curative resection; no preoperative treatment; no microscopic residual tumor; no history of transplantation and/or immunosuppression; no evidence of infection, such as pneumonia, prior to surgery; no treatment for concomitant autoimmune diseases with immunosuppressive therapy; no history of hematological malignancy, including malignant lymphoma and leukemia; and availability of laboratory data and follow-up information.

A peripheral venous blood sample was collected from each patient within a month prior to surgery. A blood test was performed using a fully automated blood cell counting system. Histological classification was performed according to the WHO guidelines (8). Disease staging was based on the 7th edition of the TNM classification of malignant tumors (9). Study approval was granted by the Ethics Committee of the Tazuke Kofukai Medical Research Institute, Kitano Hospital.

The following clinical characteristics were retrieved from the available clinical records: age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, smoking history, pathological stage, pathological tumor status, pathological lymph node status, pleural invasion, peripheral platelet count and MPV.

Disease-free survival (DFS) was measured from the date of surgery until the date of disease recurrence or death, or until the date the patient was last known to be disease-free. OS was measured from the date of surgery until the date of death from any cause or until the date on which the patient was last known to be alive. We estimated DFS and OS employing the Kaplan-Meier analysis (10). Differences between survival curves were tested for statistical significance using the two-tailed log-rank test. Univariate and multivariate prognostic analyses were performed for OS and DFS outcomes using the Cox proportional hazards model. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off value for MPV; values with maximum joint sensitivity and specificity were selected. Categorical variables were compared using the χ² test and continuous variables were compared using the t-test. All the statistical analyses were performed employing the R statistical software, version 2.13.1 (R Foundation for Statistical Computing, Vienna, Austria). All the P-values are two-sided and P-values <0.05 were considered to indicate statistically significant differences.

Data from 373 patients diagnosed with NSCLC who underwent surgery at our hospital between January, 2007 and December, 2011 were reviewed from the hospitals database and 65 patients were excluded due to preoperative treatment (n=20), incomplete resection (n=37) and history of hematological disorders (n=8). Thus, 308 patients were finally included in this study. The clinicopathological characteristics of the patients are summarized in Table I. The patients included 164 men and 144 women, with a median age at the time of surgery of 69 years (range, 19–87 years). The median follow-up duration was 36.0 months (range, 1.0–77.4 months). A total of 64 patients received postoperative adjuvant chemotherapy and 64 patients experienced NSCLC recurrence. The 5-year DFS and OS rate of all 308 patients were 66.2% (pathological stage I, 76.5%; pathological stage II, 39.6%; and pathological stage IIIA, 33.5%) and 80.5% (pathological stage I, 85.1%; pathological stage II, 78.3%; and pathological stage IIIA, 56.9%), respectively.

The ROC curve for MPV was used to determine the cut-off values. The area under the curve for MPV was 0.641 [95% confidence interval (CI): 0.562–0.719]. An MPV of 8.50 fl corresponded to the maximum joint sensitivity and specificity on the ROC curve (87.2% sensitivity and 44.1% specificity). The associations between MPV and the clinicopathological factors in this study population are shown in Table I. A low MPV was not found to be significantly associated with any other clinicopathological factor.

The Kaplan-Meier analysis was performed to determine whether MPV was associated with DFS and OS. The DFS was significantly shorter in the group with a MPV of <8.50 fl compared to that in the group with a MPV of ≥8.50 fl (P=0.011; Fig. 1A). The 5-year DFS rate in the <8.50 fl and ≥8.50 fl groups was 60.8 and 74.4%, respectively. The OS in the group with a MPV of <8.50 fl was significantly inferior to that in the group with a MPV of ≥8.50 fl (P=0.001; Fig. 1B). The 5-year OS rate in the two groups was 73.6 and 93.3%, respectively.

We also evaluated the effect of MPV on the prognosis of the 244 patients who did not receive adjuvant chemotherapy, employing the Kaplan-Meier analysis. The DFS of the group with a MPV of <8.50 fl was significantly shorter compared to that in the group with a MPV of ≥8.50 fl (P=0.030; Fig. 2A). The 5-year DFS rate in the <8.50 and ≥8.50 fl groups was 66.8 and 81.6%, respectively. The group with a MPV of <8.50 fl experienced a significantly inferior OS compared to that in the group with a MPV of ≥8.50 fl (P<0.001; Fig. 2B). The 5-year OS rate in the two groups was 74.8 and 97.0%, respectively.

The univariate analysis identified seven significant risk factors for DFS, namely age, gender, smoking history, tumor status, lymph node status, histology and MPV (Table II). In the multivariate analysis, a low MPV was shown to be a statistically significant independent predictor of DFS, [hazard ratio (HR)=1.713; 95% CI: 1.070–2.742, P=0.025]. The other independent prognostic factors were age (HR=1.753; 95% CI: 1.127–2.727, P=0.013), tumor status (HR=1.716; 95% CI: 1.063–2.770, P=0.027) and lymph node status (HR=3.493; 95% CI: 2.144–5.689, P<0.001).

As regards OS, the univariate analysis identified seven significant risk factors, namely age, gender, smoking history, tumor status, lymph node status, histology and MPV (Table III). The multivariate analysis identified low MPV as a statistically significant independent prognostic factor of OS (HR=2.835; 95% CI: 1.304–6.163, P=0.009). The other independent prognostic factors were age (HR=4.466; 95% CI: 2.223–8.972, P<0.001) and lymph node status (HR=3.654; 95% CI: 1.881–7.098, P<0.001).