Participant characteristics
The study population consisted of 133 patients who underwent surgery for lung cancer. The characteristics of the patients are shown in Table 2. The 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, 14.2%; 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%) had 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. 263 U/mL) and the number of HSP47-positive fibroblasts in the cancer stroma (71 vs. 125) 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 cut-off level for discriminating between high and low numbers of HSP47-positive fibroblasts was 73. Thus, 91 patients (68.4%) had a high number of HSP47-positive fibroblasts (Table 3). The group with a high number of HSP47-positive fibroblasts had a greater proportion of male patients (74.7% vs 45.2%), patients with a history of smoking (71.8% vs 39.5%), patients with pN1 or pN2 classification (23.1% vs 4.8%), and patients who showed recurrence (29.7% vs 4.8%) and higher scores on the Brinkman index (900 vs. 620) than those in the group with a low number of HSP47-positive fibroblasts. However, the proportion of patients who had adenocarcinoma was lower in the group with a high number of HSP47-positive fibroblasts (62.6% 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 4.665 95% CI 1.642–16.82, p = 0.003), and a high number of HSP47-positive fibroblasts in the cancer stroma (OR 8.437, 95% CI 2.351–54.07, p = 0.004) as significant risk factors for the recurrence of lung cancer after surgery (Table 4). In contrast, 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 4.371, 95% CI 1.054–29.83, p = 0.042) (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 < 0.001, log-rank test, cut-off value = 123). 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), and a high number of HSP47-positive fibroblasts (OR 4.627, 95% CI 1.990–11.23, p < 0.001) to be significant risk factors for death because of lung cancer after surgery. However, multivariate analysis did not identify any independent risk factor for death from lung cancer after surgery (Additional file 2).
The DFS curves based on HSP47 expression status in cancer cells and the number of HSP47-positive fibroblasts in adenocarcinoma patients exhibited similar differences to those in all patients (Additional file 3). No significant differences were observed in either the DFS or OS curves based on HSP47 expression status in cancer cells and the number of HSP47-positive fibroblasts in patients with squamous cell carcinoma (data not shown).