3.1 Patient characteristics
Fig.1 visually illustrates the patient selection process, while Table 2 summarizes patient characteristics. This study included 130 participants (71 males and 59 females) with a mean age of 43.92±12.52 years. Histological analysis confirmed 98 cases of adamantinomatous craniopharyngioma (ACP) and 32 cases of papillary craniopharyngioma (PCP). The mean duration of follow-up was 22.67±9.29 months. Calcification was observed in 61.5% of the cohort (n=80). Preoperative hydrocephalus and preoperative visual field damage were present in 26.2% (n=34) and 17.7% (n=23) of patients, respectively. Regarding preoperative body weight, 60 patients had normal weight, 56 were overweight, and 14 were obese. Gonadotropic hormone deficiency (n=34, 26.2%) and antidiuretic hormone deficiency (n=32, 24.6%) were the two most common preoperative hormone deficiencies in patients with CP. The incidence of other hormone deficiencies, including growth hormone deficiency (n=19, 14.6%), thyroid-stimulating hormone deficiency (n=16, 12.3%), and adrenocorticotropic hormone deficiency (n=12, 9.2%), was less than 15%.
On preoperative MRI, severe HI (grade 2) was observed in approximately half of the patients (n=64, 49.2%), while mild HI (grade 1) and no HI (grade 0) were observed in 36.9% (n=48), and 14.6% (n=19) of patients, respectively. The mean tumor size was 3.1±0.97 cm, and the mean tumor volume was 13.01±11.82 cm3. Moreover, the mean size and mean volume of the cysts were 2.02±1.05 cm and 5.86±8.62 cm3, respectively. Among the 130 cases, 76 tumors were identified as cystic tumors. Finally, GTR was achieved in 120 patients (92.3%), and NTR was achieved in 10 patients (7.7%).
3.2 Association between inflammatory mediators, weight gain, new-onset obesity, and leptin concentration
According to the univariate logistic regression analysis, significant weight gain (weight change ≥5%) was associated with higher expression of CXCL1 (Fig.2a, unadjusted odds ratio (uOR) = 2.12, 95% confidence interval (CI), 1.05-4.28, P=0.036). New-onset postoperative obesity was associated with high expressions of CXCL1 (Fig.2c, uOR = 3.67, 95% CI, 1.11-12.15, P=0.034) and TNF (Fig.2c, uOR = 2.92, 95% CI, 1.04-9.02, P=0.045).Multivariate logistic regression analysis adjusted for age, gender, HI, and preoperative body mass index (BMI) was conducted to explore the independent relationships among inflammatory mediators, significant weight gain, and new-onset obesity. The results revealed that high expressions of CXCL1 (Fig.2b, adjusted odds ratio (aOR) = 2.21, 95% CI, 1.02-4.77, P=0.044) and CXCL8 (Fig.2b, aOR = 2.43, 95% CI, 1.08-5.51, P=0.032) were independent risk factors for significant weight gain, while high expression levels of CXCL1 (Fig.2d, aOR = 4.58, 95% CI, 1.21-17.26, P=0.025) and TNF (Fig.2d, aOR = 3.83, 95% CI, 1.10-13.31, P=0.035) were found to be independent risk factors for new-onset postoperative obesity.
Leptin, a cytokine secreted by fat cells that regulates energy balance, is abnormally elevated relative to the degree of obesity in patients with CP[14]. However, the underlying mechanisms of leptin elevation and resistance in CP remain uncertain. Therefore, we attempted to explain this abnormal elevation by investigating the relationship between the inflammatory mediators and plasma leptin. The mean plasma leptin concentration was 29.18±25.56 ng/ml, ranging from 0.5 ng/ml to 131.3 ng/ml. The plasma leptin concentration was positively correlated with expressions of CXCL1 (Fig.3a, r=0.185, P=0.036), CXCL8 (Fig.3b, r=0.204, P=0.020), and IL10 (Fig.3f, r=0.227, P=0.009), while it did not show a significant correlation with the expression levels of IL1A (P=0.208), IL1B (P=0.680), IL6 (P=0.790), and TNF (P=0.809).
3.3 Inflammatory mediators associate with clinical characteristics and progression-free survival
The mRNA expression levels of these seven inflammatory mediators were significantly higher in CP tumor tissue than in normal pituitary tissue (Fig.4, and all P <0.05, Mann Whitney U-test).
Table 3 depicts the associations between inflammatory meditator expression and clinicopathologic parameters. Compared with the PCP subtype, the ACP subtype exhibited lower levels of CXCL1, CXCL8, IL1A, and IL1B (all P<0.05) but higher levels of IL10 (P=0.027). Tumors with calcification exhibited lower CXCL1, CXCL8, IL1A, and IL1B (all P<0.01) than those without calcification. Furthermore, severe HI was associated with higher levels of CXCL1 (P=0.013) and CXCL8 (P=0.043). Moreover, higher IL6 expression and lower TNF expression were associated with preoperative hydrocephalus. Cystic tumors exhibited higher expression of IL1B, IL6, IL10, and TNF (all P<0.05) than non-cystic tumors. Furthermore, no significant associations were detected between inflammatory meditators expression and other characteristics, including age, sex, preoperative visual field damage, and preoperative obesity.
In terms of tumor size and tumor volume, tumor size was positively correlated with levels of CXCL1 (r=0.17, P=0.048), CXCL8 (r=0.18, P=0.037), and IL6 (r=0.27, P=0.009). Tumor volume was positively correlated with levels of CXCL8 (r=0.18, P=0.037) and IL6 (r=0.28, P=0.004). In contrast, TNF expression negatively correlated with tumor size (r= -0.18, P=0.040) and tumor volume (r= -0.18, P=0.040). In terms of cyst size and cyst volume, IL6 expression was positively correlated with cyst size (r=0.22, P=0.013) and cyst volume (r=0.25, P=0.005), and IL10 expression was also positively correlated with the cyst size (r=0.24, P=0.006) and cyst volume (r=0.26, P=0.002).
To determine the prognostic value of inflammatory mediators in patients with CP, we dichotomized the cohort into two groups (high and low expression groups) based on the median expression of each gene, and the details are shown in Fig.5. The K–M curves revealed that poor PFS was associated with high CXCL1 ( hazard ratio (HR)=2.33, 95% CI, 1.06-5.11, P=0.041), CXCL8 (HR=2.30, 95% CI, 1.06-4.97, P=0.037), IL1A (HR=2.56, 95% CI, 1.19-5.53, P=0.021), IL6 (HR=2.30, 95% CI, 1.05-5.03, P=0.044), and TNF (HR=2.19, 95% CI, 1.02-4.74, P=0.033) expression. However, no significant association was observed between poor PFS and the expression of IL1B (P=0.602) or IL10 (P=0.486).