Kumari Nitu, Agrawal Usha, Mishra Ashwani Kumar, Kumar Anup, Vasudeva Pawan, Mohanty Nayan Kumar, Saxena Sunita
1 National Institute of Pathology (Indian Council of Medical Research), New Delhi, India.
2 BITS Pilani, Pilani, India.
Tumour Biol. 2017 Apr;39(4):1010428317697552. doi: 10.1177/1010428317697552.
Urothelial cancer patients are prone to recurrence, and there is no marker to predict which cases become refractory to the immunotherapy given to these patients. Tumour behaviour is decided by the dynamics between the pro- and anti-tumorigenic cytokines. In this study, 27 cytokines were estimated in serum and urine of 72 urothelial cancer patients and 42 healthy volunteer controls. Serum cytokines IL-1RA, IL-4 and RANTES were in significantly higher concentration in serum of patients compared to controls, while IL-2 was significantly less in concentration. Patients were found to have significantly high concentrations of 12 urinary cytokines (IL-2, IL-4, IL-8, IL-10, GM-CSF, IFN-γ, IP-10, MIP-1a, PDGF, MIP-1b, RANTES and VEGF) in comparison to healthy controls. Serum VEGF and urinary IL-1ra, IL-4, IL-10, GM-CSF, IP-10, MIP-1a and MIP-1b concentrations were found significantly higher in concentration in high-grade tumours compared to low-grade tumours. There was no difference in either the serum or urinary cytokines between non-invasive and muscle-invasive cases. Serum IL-1ra, IL-6, IL-10, TNF-α and VEGF and urinary IL-1ra, IL-4, IL-8, IL-10, GM-CSF, IP-10, MIP-1a, PDGF, MIP-1b and VEGF were found to be significantly higher in recurrent patients compared to non-recurrent patients. Of these, high concentrations of urinary IL-1RA, IL-4, IL-10, IP-10, PDGF and VEGF and serum IL-1ra, IL-6, IL-10, VEGF and TNF-α were associated with poor recurrence-free survival. Poor recurrence-free survival was also seen with increasing number of cytokines showing high concentrations. The study shows that the estimation of a combination of these cytokines in minimally or non-invasive samples may act as a prognostic indicator.
尿路上皮癌患者容易复发，且没有标志物可预测哪些病例会对给予这些患者的免疫治疗产生耐药性。肿瘤行为由促肿瘤和抗肿瘤细胞因子之间的动态关系决定。在本研究中，对72例尿路上皮癌患者和42例健康志愿者对照的血清和尿液中的27种细胞因子进行了评估。与对照组相比，患者血清中的细胞因子IL-1RA、IL-4和RANTES浓度显著更高，而IL-2浓度显著更低。与健康对照相比，患者尿液中12种细胞因子（IL-2、IL-4、IL-8、IL-10、GM-CSF、IFN-γ、IP-10、MIP-1a、PDGF、MIP-1b、RANTES和VEGF）的浓度显著更高。与低级别肿瘤相比，高级别肿瘤的血清VEGF以及尿液IL-1ra、IL-4、IL-10、GM-CSF、IP-10、MIP-1a和MIP-1b浓度显著更高。非侵袭性和肌肉侵袭性病例之间的血清或尿液细胞因子没有差异。与未复发患者相比，复发患者的血清IL-1ra、IL-6、IL-10、TNF-α和VEGF以及尿液IL-1ra、IL-4、IL-8、IL-10、GM-CSF、IP-10、MIP-1a、PDGF、MIP-1b和VEGF显著更高。其中，尿液中高浓度的IL-1RA、IL-4、IL-10、IP-10、PDGF和VEGF以及血清中IL-1ra、IL-6、IL-10、VEGF和TNF-α与无复发生存期差有关。随着显示高浓度的细胞因子数量增加，无复发生存期也较差。该研究表明，在微创或非侵入性样本中对这些细胞因子进行联合评估可能作为一种预后指标。
