Combination of Blood Adiponectin and Leptin Levels Is a Predictor of Biochemical Recurrence in Prostate Cancer Invading the Surrounding Adipose Tissue

Abstract

Biochemical recurrence is a process that progresses to castration-resistant prostate cancer (CRPC) and prediction of biochemical recurrence is useful in determining early therapeutic intervention and disease treatment. Prostate cancer is surrounded by adipose tissue, which secretes adipokines, affecting cancer progression. This study aimed to investigate the correlation between blood adipokines and CRPC biochemical recurrence. We retrospectively analyzed the clinical data, including preoperative serum adipokine levels, of 99 patients with pT3a pN0 prostate cancer who underwent proctectomy between 2011 and 2019. The primary outcome was biochemical recurrence (prostate-specific antigen: PSA > 0.2). We identified 65 non-recurrences and 34 biochemical recurrences (one progressed to CRPC). The initial PSA level was significantly higher (p = 0.006), but serum adiponectin (p = 0.328) and leptin (p = 0.647) levels and their ratio (p = 0.323) were not significantly different in the biochemical recurrence group compared with the non-recurrence group. In contrast, significantly more biochemical recurrences were observed in the group with adiponectin < 6 μg/mL and Leptin < 4 ng/mL (p = 0.046), initial PSA > 15 ng/mL, clinical Gleason pattern ≥ 4, and positive resection margin. A significant difference was also observed in the multivariate analysis (hazard ratio: 4.04, 95% confidence interval: 1.21-13.5, p = 0.0232). Thus, low preoperative serum adiponectin and high leptin levels were significantly associated with biochemical recurrence in adipose tissue-invasive prostate cancer, suggesting that they may be useful predictors of biochemical recurrence. Further studies with larger cases are needed to increase the validity of this study.

Keywords: adipocytes; adipokine; adiponectin; androgen receptor; biochemical recurrence; castration-resistant prostate cancer; leptin; prostate cancer.

Figure 1

Patient selection flow chart. A total of 134 patients underwent total prostatectomy and had pathological phenotypes of pT3 or higher stages of the disease. Of these patients, 35 had pT3b, pT4, or pN0 stages of the disease and were excluded, 34 had biochemical recurrences, and 65 had non-recurrences. Of the 34 biochemical recurrences, one developed CRPC. CRPC, castration-resistant prostate cancer.

Figure 2

Analysis of differences in age, body mass index, and initial PSA between patients with and without biochemical recurrence. Age (left), BMI (middle), and initial PSA (right) were compared between patients with (n = 34) and without (n = 65) biochemical recurrence. Statistical analyses were performed using unpaired t-tests. BMI, body mass index; y, year. * p < 0.05.

Figure 3

Analysis of differences in preoperative serum adiponectin and leptin concentrations and adiponectin/leptin ratios between patients with and without biochemical recurrence. Serum adiponectin concentration (left), serum leptin concentration (middle), and A/L ratio (right) were compared between patients with (n = 34) and without biochemical recurrence (n = 65). Statistical analyses were performed using the unpaired t-test. A/L ratio, adiponectin/leptin ratio.

Figure 4

Analysis of differences in preoperative serum adiponectin (left), leptin (middle), and adiponectin/leptin ratios (right) in patients with biochemical recurrence and the duration for biochemical recurrence. We compared the correlation between the duration from surgery to biochemical recurrence and preoperative serum adiponectin concentration, leptin concentration, A/L ratio, or the presence of adiponectin (<6 μg/mL) and leptin (>4 ng/mL) among patients (n = 34) who developed biochemical recurrence. Statistical analyses were performed using the unpaired t-test. A/L ratio, adiponectin/leptin ratio. ns: not significant (p > 0.05).

Figure 5

Receiver operating characteristic curves for a population of 99 patients with a pT3a pN0 stage of the disease with preoperative adiponectin of <6 μg/mL and leptin of >4 ng/mL. The sensitivity and specificity for biochemical recurrence in the population of patients were 89.2% and 27.3%, respectively. ROC, receiver operating characteristic. Black solid line: ROC for predicting biochemical recurrence; red dotted line: reference line.

Figure 6

Analysis of differences in preoperative adiponectin/leptin ratios among cases without biochemical recurrence, cases with biochemical recurrence and without CRPC, and cases with CRPC. Preoperative A/L ratios were compared among the three groups of patients without biochemical recurrence (n = 74), with biochemical recurrence and without CRPC (n = 52), and cases with CRPC (n = 8). Statistical analyses were performed using the Kruskal–Wallis test. Rec, recurrence; A/L ratio, adiponectin/leptin ratio; and CRPC, castration-resistant prostate cancer.