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Journal of Peking University (Health Sciences) ›› 2021, Vol. 53 ›› Issue (2): 302-307. doi: 10.19723/j.issn.1671-167X.2021.02.012

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Clinical value of inflammatory biomarkers in predicting prognosis of patients with ureteral urothelial carcinoma

CHEN Huai-an,LIU Shuo(),LI Xiu-jun,WANG Zhe,ZHANG Chao,LI Feng-qi,MIAO Wen-long   

  1. Department of Urology, the First Affiliated Hospital, Hebei North Univercity, Zhangjiakou 075061, Hebei, China
  • Received:2019-03-25 Online:2021-04-18 Published:2021-04-21
  • Contact: Shuo LIU E-mail:liushuo1970@163.com
  • Supported by:
    Government-funded Project on Training Outstanding Clinical Medical Talents and Basic Research Projects in 2017(冀财社[2017]46号)

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Abstract:

Objective: To evaluate the clinical value of inflammation-related markers in predicting the prognosis of patients with ureteral urothelial carcinoma. Methods: 200 patients with ureteral urothelial carcinoma were randomly divided into two groups by split sample validation: modeling group and validation group. Paraffin embedded pathological specimens of the patients were reviewed. Immunohistochemical method was used to detect tumor-infiltrating neutrophil (TIN) (CD66b+), tumor-associated macrophage (TAM) (CD163+), lymphocyte (CD+, CD4+, CD8+) counts, peripheral blood neutrophil / lymphocyte ratio (NLR) and tumor tissue neutrophil/monocyte ratio (NMR). According to the results of pathological staging, the patients were divided into non-muscle-invasive and muscle-invasive ureteral urothelial carcinoma group. The resolution of the models was evaluated, and the prognostic nomogram models including only peripheral blood parameters and all parameters were established to compare the accuracy of the two models in predicting the prognosis of patients with urothelial carcinoma of the ureter. Results: The median follow-up time was 36 months, the progression-free survival was 40 months, and 42 cases (21.0%) showed tumor progression within 3 years. Tumor size, pathological stage and pathological grade were all single-factor variables predicting the first recurrence of ureteral urothelial carcinoma three years after operation. Tumor size, pathological stage, pathological grade, TIN, TAM, NLR and NMR were multi-factor variables predicting the first recurrence three years after operation. Among 104 cases of non-muscle-invasive ureteral urothelial carcinoma, 10 cases (9.6%) recurred for the first time 3 years after operation, 96 cases (33.3%) of muscle invasive ureteral urothelial carcinoma, and the diffe-rence between the two groups was statistically significant (χ2=15.53, P<0.05). The predictive nomogram model of progression free survival was established. The concordance index of progression free survi-val was 0.722 (95%CI: 0.70-0.78) in non-muscle-invasion group, and 0.725 (95%CI: 0.71-0.79) in muscle-invasion group, which was in good agreement with the observed 3-year survival rate. The results of discrimination test showed that the concordance index of the whole parameter prediction model of ureteral urothelial carcinoma was 0.726, which was higher than that of peripheral blood parameters (consistency index 0.672). The immune microenvironment of ureteral urothelial carcinoma improved the prediction accuracy of the model. Conclusion: The prognosis prediction model based on immune inflammation-related markers was established as a perfection and supplement for the existing pathological grading and staging system, providing a basis for accurate individualized treatment of patients with urete-ral urothelial carcinoma. The prognosis prediction model based on the relevant indicators of peripheral blood samples is established, which is easy to obtain specimens, and the detection method is simple and economical, which is more conducive to clinical application.

Key words: Ureteral neoplasms, Biomarkers, Linear models, Inflammation, Prognosis

CLC Number: 

  • R737.13

Table 1

General information, pathological characteristics, inflammatory immune related factors analysis of the model group (n=160) and the verification group (n=40)"

Items n Modeling group, n(%) Verification group, n(%) χ2/t P
Age, n(%) 1.21 0.27
30-50 years 93 78 (48.8) 15 (37.5)
51-76 years 107 82 (51.2) 25 (62.5)
Gender, n(%) 0.99 0.32
Male 129 100 (62.5) 29 (72.5)
Female 71 60 (37.5) 11 (27.5)
Tumor size, n(%) 0.03 0.86
<2 cm 90 60 (37.5) 30 (75.0)
2-4 cm 110 100 (62.5) 10 (25.0)
Pathological grading, n(%) 0 0.97
Low level 102 82 (51.2) 20 (50.0)
High level 98 78 (48.8) 20 (50.0)
Operative methods, n(%) 2.32 0.13
Retroperitoneal laparoscopy 106 80 (50.0) 26 (65.0)
Traditional open surgery 94 80 (50.0) 14 (35.0)
Pathological staging, n(%) 2.39 0.12
T3 40 36 (22.5) 4 (10.0)
T1-T2 160 124 (77.5) 36 (22.5)
TIN, $\bar{x} \pm s$ 200 56.7±10.4 54.8±10.8 1.03 0.31
TAM, $\bar{x} \pm s$ 200 57.9±11.3 58.9±11.5 0.50 0.62
NLR, $\bar{x} \pm s$ 200 3.3±0.6 3.4±0.7 0.91 0.36
NMR, $\bar{x} \pm s$ 200 2.6±0.7 2.5±0.6 0.83 0.41

Table 2

Univariate analysis of predicting the first recurrence of ureteral and urothelial carcinoma after operation"

Influence factor Sub-item RR Wald Z P 95%CI for Exp(B)
Tumor size <2 cm / 2-4 cm 0.653 18.590 <0.001 1.528-3.904
Pathological staging T1-T2/T3 1.609 13.598 <0.001 1.695-5.395
Pathological grading Low level / High level 2.295 16.281 <0.001 1.793-6.683

Table 3

Multivariate cox regression analysis for predicting recurrence of ureteral epithelial carcinoma"

Influence factor B S.E. Wald Z df P Exp(B) 95%CI for Exp(B)
Tumor size 0.877 0.547 17.624 1 <0.001 2.403 1.428-3.897
Pathological staging 1.849 1.307 12.635 1 0.003 3.936 1.695-5.276
Pathological grading 2.109 1.984 14.365 1 <0.001 4.309 1.789-6.593
TIN 1.674 1.714 21.573 1 <0.001 2.582 1.823-3.517
TAM 2.136 1.532 13.621 1 <0.001 3.134 1.634-4.186
NLR 1.727 1.635 18.379 1 <0.001 2.658 1.534-3.626
NMR 2.025 1.421 12.517 1 <0.001 3.012 1.525-4.072

Figure 1

Full-parameter model correction chart for predicting progression-free survival after myometrial invasive (A) and non-muscular invasive (B) surgery for ureteral epithelial carcinoma"

Figure 2

Calibration chart of nomogram model for predicting progression free survival rate with full parameters (A) and peripheral blood parameters (B)"

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