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Journal of Peking University (Health Sciences) ›› 2022, Vol. 54 ›› Issue (4): 605-614. doi: 10.19723/j.issn.1671-167X.2022.04.005

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Correlation between adipokine and clinicopathological features and prognosis in upper tract urothelial carcinoma

Xiang DAI,Fei WANG,Yi-qing DU,Yu-xuan SONG,Tao XU*()   

  1. Department of Urology, Peking University People's Hospital, Beijing 100044, China
  • Received:2022-03-14 Online:2022-08-18 Published:2022-08-11
  • Contact: Tao XU E-mail:xutao@pkuph.edu.cn

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Abstract:

Objective: To investigate the correlation between expression levels of adipokine and clinicopathological features and prognosis of patients with upper tract urothelial carcinoma (UTUC) based on immunohistochemical staining and bioinformatics analysis. Methods: The 8 adipokines in this study included adiponectin (AdipoQ), leptin (LEP), interleukin (IL)-6, IL-10 and their receptors (AdipoR1, AdipoR2, LEPR, IL-6R, IL-10RA, IL-10RB). Tissue samples of patients with UTUC who underwent surgical treatment in Peking University People's Hospital from January 2014 to April 2021 were selected for immunohistochemical staining. Their quantitative gene expression data were calculated by H-Score, and relevant clinical and follow-up data were collected retrospectively. Transcription group sequencing data of UTUC patients in Gene Expression Omnibus database (GSE134292 dataset) were downloaded for comparison. Chi-square test or t-test was used to compare the expression level of adipokine between non-muscle invasive group and muscle invasive group. Univariate and multivariate Cox regression analysis and Kaplan-Meier survival curve were utilized to analyze independent predictors of overall survival (OS), disease-free survival (DFS), intravesical recurrence-free survival (IVRFS) in the both cohorts. The P < 0.05 was considered statistically significant. Results: In the study, 63 tissue samples of the patients with UTUC who underwent surgical treatment in Peking University People's Hospital and 57 UTUC patients in GSE134292 dataset were selected. In immunohistochemical cohort, the expressions of AdipoQ (P=0.003 6), AdipoR1 (P=0.006 5), LEP (P=0.007 7), IL-10 (P=0.006 9), and IL-10RA (P=0.008 9) were statistically higher in muscle invasive group. In GSE134292 cohort, the expressions of AdipoR1 (P=0.000 4), AdipoR2 (P=0.000 4), IL-6 (P=0.005 0), IL-10 (P=0.001 7), and IL-10RA (P=0.008 1) were statistically higher in muscle invasive group. Kaplan-Meier survival curve and multivariate Cox regression analysis showed that high IL-10RA expression was an independent predictive factor of IVRFS (P=0.044, HR=0.996, 95%CI: 0.992-0.998) in immunohistochemical cohort, which was confirmed in GSE134292 cohort (P=0.014, HR=0.515, 95%CI: 0.304-0.873). Conclusion: The expression levels of AdipoQ, AdipoR1, IL-10, and IL-10RA were correlated with tumor stage, suggesting that these adipokines played important roles in tumor progression. IL-10RA was an independent predictor of IVRFS, suggesting that IL-10 and its receptor played a critical role in tumor recurrence.

Key words: Upper tract urothelial carcinoma, Adipokine, Immunohistochemical

CLC Number: 

  • R737.1

Figure 1

Immunohistochemical staining result of adipokines and receptors in immunohistochemical cohort (×400) 1, AdipoQ; 2, AdipoR1; 3, AdipoR2; 4, LEP; 5, IL-6; 6, IL-6R; 7, IL-10; 8, IL-10RA; A, low-expression; B, high-expression. AdipoQ, adiponectin; LEP, leptin; IL, interleukin; R, receptor."

Table 1

Clinicopathological characteristics of UTUC patients in two cohorts"

Items IHC cohort GSE134292 cohort P value
Number 63 57
Age/years 68.25±9.26 68.58±10.45 0.858
Gender Male 38 (60.3) 37 (64.9) 0.607
Female 25 (39.7) 20 (35.1)
T stage Ta-T1 35 (55.6) 26 (45.6) 0.281
T2-T4 28 (44.4) 31 (54.4)
Grade Low-grade 15 (23.8) 12 (21.1) 0.721
High-grade 48 (76.2) 45 (78.9)

Figure 2

Gene expression in different tumor stages in immunohistochemical cohort TPM, transcripts per kilobase per million mapped reads; AdipoQ, adiponectin; LEP, leptin; IL, interleukin; R, receptor."

Figure 3

Gene expression in different tumor stages in GSE134292 cohort Abbreviations as in Figure 2."

Table 2

Univariate and multivariate Cox regression analysis in immunohistochemical cohort"

Items OS
Univariate Multivariate
P HR 95%CI P HR 95%CI
Age 0.239 2.264 0.581-8.821
Gender 0.847 1.133 0.320-4.018
T stage 0.046 6.669 1.020-54.223
Grade 0.427 2.324 0.291-18.579
Tumor diameter 0.813 0.871 0.278-2.734
Multifocality 0.614 0.670 0.141-3.176
AdipoQ 0.542 0.996 0.985-1.008
AdipoR1 0.342 1.008 0.992-1.024
AdipoR2 0.968 1.000 0.985-1.015
LEP 0.371 0.994 0.982-1.007
IL-6 0.960 0.999 0.977-1.023
IL-6R 0.900 1.001 0.988-1.014
IL-10 0.309 0.986 0.961-1.013
IL-10RA 0.585 1.003 0.993-1.012
Items DFS
Univariate Multivariate
P HR 95%CI P HR 95%CI
Age 0.063 2.002 0.962-4.167 0.623 1.251 0.512-3.055
Gender 0.265 0.642 0.295-1.398
T stage 0.001 11.048 3.794-32.174 0.001 13.962 3.159-61.710
Grade 0.055 3.237 0.976-10.735 0.453 0.547 0.113-2.647
Tumor diameter 0.034 2.271 1.065-4.842 0.305 1.507 0.688-3.297
Multifocality 0.855 1.079 0.477-2.442
AdipoQ 0.363 1.003 0.997-1.009
AdipoR1 0.044 1.009 1.000-1.017 0.921 1.001 0.989-1.013
AdipoR2 0.477 1.004 0.994-1.014
LEP 0.223 1.004 0.998-1.010
IL-6 0.135 1.009 0.997-1.020
IL-6R 0.879 1.001 0.993-1.009
IL-10 0.194 1.008 0.996-1.020
IL-10RA 0.073 0.996 0.991-1.000 0.538 1.002 0.996-1.008
Items IVRFS
Univariate Multivariate
P HR 95%CI P HR 95%CI
Age 0.084 1.038 0.995-1.082 0.586 1.277 0.529-3.083
Gender 0.258 0.622 0.273-1.415
T stage 0.001 45.300 6.093-336.812 0.001 14.418 3.292-63.149
Grade 0.043 4.451 1.048-18.898 0.453 0.545 0.112-2.655
Tumor diameter 0.009 3.054 1.319-7.069 0.307 1.504 0.688-3.288
Multifocality 0.554 1.287 0.558-2.964
AdipoQ 0.154 1.005 0.998-1.011
AdipoR1 0.056 1.009 1.000-1.018 0.975 1.000 0.989-1.010
AdipoR2 0.422 1.004 0.994-1.015
LEP 0.115 1.005 0.999-1.011
IL-6 0.283 1.007 0.995-1.019
IL-6R 0.945 1.000 0.991-1.008
IL-10 0.098 1.010 0.998-1.022 0.863 1.002 0.998-1.004
IL-10RA 0.017 0.994 0.989-0.999 0.044 0.996 0.992-0.998

Table 3

Univariate and multivariate Cox regression analysis in GSE134292 cohort"

Items OS
Univariate Multivariate
P HR 95%CI P HR 95%CI
Age 0.723 1.008 0.966-1.052
Gender 0.830 1.108 0.434-2.829
T stage 0.004 6.108 1.766-21.119 0.043 4.330 1.047-17.905
Grade 0.222 27.340 0.134-5559.469
Tumor location 0.614 1.329 0.440-4.016
AdipoQ 0.450 1.905 0.358-10.137
AdipoR1 0.025 2.077 1.096-3.935 0.713 1.276 0.348-4.681
AdipoR2 0.011 1.950 1.169-3.253 0.915 1.066 0.330-3.449
LEP 0.522 1.338 0.548-3.267
IL-6 0.014 1.359 1.065-1.734 0.417 1.203 0.770-1.878
IL-6R 0.995 0.999 0.632-1.577
IL-10 0.545 1.390 0.479-4.032
IL-10RA 0.036 1.420 1.023-1.971 0.649 0.889 0.535-1.477
Items DFS
Univariate Multivariate
P HR 95%CI P HR 95%CI
Age 0.435 0.990 0.964-1.016
Gender 0.408 1.299 0.700-2.411
T stage 0.059 1.814 0.979-3.360 0.189 1.555 0.805-3.005
Grade 0.169 1.720 0.795-3.721
Tumor location 0.124 1.873 0.841-4.168
AdipoQ 0.667 1.341 0.352-5.101
AdipoR1 0.077 1.499 0.957-2.350 0.345 1.264 0.777-2.056
AdipoR2 0.126 1.355 0.918-2.000
LEP 0.086 1.652 0.932-2.928 0.318 1.384 0.731-2.622
IL-6 0.659 1.044 0.864-1.261
IL-6R 0.619 1.070 0.820-1.396
IL-10 0.311 1.529 0.672-3.475
IL-10RA 0.315 1.157 0.871-1.539
Items IVRFS
Univariate Multivariate
P HR 95%CI P HR 95%CI
Age 0.133 0.977 0.948-1.007
Gender 0.829 1.085 0.516-2.283
T stage 0.536 0.797 0.388-1.638
Grade 0.870 0.934 0.414-2.109
Tumor location 0.015 3.049 1.245-7.464 0.046 2.491 1.014-6.115
AdipoQ 0.239 0.026 0.001-11.313
AdipoR1 0.935 1.019 0.646-1.607
AdipoR2 0.490 0.847 0.529-1.357
LEP 0.317 0.499 0.128-1.947
IL-6 0.119 0.795 0.595-1.061
IL-6R 0.137 0.751 0.515-1.095
IL-10 0.067 0.279 0.071-1.093 0.720 1.397 0.225-8.694
IL-10RA 0.008 0.496 0.294-0.836 0.014 0.515 0.304-0.873

Figure 4

Kaplan-Meier survival curve of IL-10RA for IVRFS in immunohistochemical cohort (A) and GSE134292 cohort (B) IL, interleukin; R, receptor; IVRFS, intravesical recurrence-free survival."

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