Subject characteristics
The study population consisted of 133 patients who underwent surgery for lung cancer. The characteristics of the patients are shown in Table 2. Median patient age was 70 years (male patients, 87 (65.4%)). Seventy-six patients had a history of smoking (61.8%), and 99 patients showed adenocarcinoma (74.4%). The percentages of patients showing each pathological stage of lung cancer were as follows: stage I, 77.4%; stage II, 14.5%; stage III, 7.6%; and stage IV, 0.9%.
Comparison of patient characteristics between patients with HSP47-positive and HSP47-negative lung cancer cells
Sixty-seven patients (48.5%) showed HSP47-positive cancer cells (Table 3). Patients with HSP47-positive cancer cells showed a greater frequency of smoking history (48.4% vs. 27.9%), higher percentage of diffusing capacity for carbon monoxide (97.6% vs. 80.9%), and a greater frequency of adenocarcinomas (89.6% vs. 59.1%) than those with HSP47-negative cancer cells. In contrast, serum KL-6 levels (193 U/mL vs. 262.5 U/mL) and the number of HSP47-positive fibroblasts in the cancer stroma (71 vs. 124.8) were lower in the HSP47-positive group than in the HSP47-negative group.
Comparison of patient characteristics between patients with high and low number of HSP47-positive fibroblasts in the cancer stroma
The optimum cutoff level for discriminating between high and low numbers of HSP47-positive fibroblasts according to the ROC curve analysis was 73. Thus, 83 patients (62.4%) showed a high number of HSP47-positive fibroblasts (Table 3). The group with a high number of HSP47-positive fibroblasts showed a greater proportion of male patients (74.7% vs 50.0%), patients with a history of smoking (71.4% vs 45.7%), patients with pT3 or pT4 classification (9.6% vs 0.0%), patients with pN1 or pN2 classification (24.1% vs 6.0%), and patients who showed recurrence (31.3% vs 6.0%) and higher scores on the Brinkman index (945 vs. 710) than those in the group with a low number of HSP47-positive fibroblasts. However, the proportion of patients showing adenocarcinoma was lower in the group with a high number of HSP47-positive fibroblasts (59.0% vs 100.0%) than in the group with a low number of HSP47-positive fibroblasts.
Survival curve and risk factors for recurrence and death
Figure 2 shows the DFS curves according to the presence or absence of HSP47 expression in cancer cells, and high or low numbers of HSP47-positive fibroblasts in the cancer stroma. The HSP47-positive and HSP47-negative groups showed no significant differences (p = 0.372, log-rank test). However, patients with a high number of HSP47-positive fibroblasts had a shorter DFS than those with few HSP47-positive fibroblasts (p = 0.001, log-rank test). Logistic regression analysis identified male sex (odds ratio [OR] 6.109, 95% confidence interval [CI] 1.987–26.75, P < 0.001), history of smoking (OR 4.664, 95% CI 1.642–16.82, P = 0.003), pT3 or pT4 classification (OR 7.014, 95% CI 1.611–36.14, P = 0.010), pN1 or pN2 classification (OR 4.685, 95% CI 1.754–14.40, P = 0.002), and a high number of HSP47-positive fibroblasts in the cancer stroma (OR 7.146, 95% CI 2.329–31.27, P < 0.001) as significant risk factors for the recurrence of lung cancer after surgery (Table 4). On the contrary, logistic regression analysis revealed adenocarcinoma to be inversely associated with recurrence (OR 0.362, 95% CI 0.149–0.886, P = 0.027). However, multivariate analysis identified only a high number of HSP47-positive fibroblasts in the cancer stroma as an independent risk factor for recurrence of lung cancer after surgery (OR 4.086, 95% CI 1.116–19.68, P = 0.033) (Table 4).
The OS curves based on HSP47 expression in cancer cells and high or low numbers of HSP47-positive fibroblasts are shown in additional file 1. There was no significant difference between the HSP47-positive and HSP47-negative groups (p = 0.388, log-rank test). However, patients with a high number of HSP47-positive fibroblasts had a shorter OS than those with a low number of HSP47-positive fibroblasts (p = 0.002, log-rank test). Logistic regression analysis identified age (OR 1.055, 95% CI 1.007–1.109, P = 0.028), male sex (OR 22.50, 95% CI 4.535–408.2, P < 0.001), history of smoking (OR 11.70, 95% CI 3.243–75.17, P < 0.001), pN1 or pN2 classification (OR 4.390, 95% CI 1.680–11.55, P = 0.028), pM1 classification (OR 4.261, 95% CI 1.194–50.32, P = 0.002), and a high number of HSP47-positive fibroblasts (OR 3.879, 95% CI 1.477–12.20, P = 0.049) to be significant risk factors for death because of lung cancer after surgery. However, there was no independent risk factor for death because of lung cancer after surgery as identified by multivariate analysis (Additional file 2).
The DFS and OS curves based on HSP47 expression status in cancer cells and the number of HSP47-positive fibroblasts in only adenocarcinoma patients showed similar differences as those in all patients. Only in patients with squamous cell carcinoma, no significant differences were observed in the DFS or OS curves based on HSP47 expression status in cancer cells and the number of HSP47-positive fibroblasts (data not shown).