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Predictive role of serum and urinary cytokines in invasion and recurrence of bladder cancer.

Abstract 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.
PMID
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Authors

Mayor MeshTerms
Keywords

Immune response

bladder cancer

cytokines

non-invasive marker

Journal Title tumour biology : the journal of the international society for oncodevelopmental biology and medicine
Publication Year Start




PMID- 28378639
OWN - NLM
STAT- MEDLINE
DA  - 20170405
DCOM- 20170410
LR  - 20170410
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 39
IP  - 4
DP  - 2017 Apr
TI  - Predictive role of serum and urinary cytokines in invasion and recurrence of
      bladder cancer.
PG  - 1010428317697552
LID - 10.1177/1010428317697552 [doi]
AB  - 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-gamma, 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-alpha 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-alpha 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.
FAU - Kumari, Nitu
AU  - Kumari N
AD  - 1 National Institute of Pathology (Indian Council of Medical Research), New
      Delhi, India.
AD  - 2 BITS Pilani, Pilani, India.
FAU - Agrawal, Usha
AU  - Agrawal U
AD  - 1 National Institute of Pathology (Indian Council of Medical Research), New
      Delhi, India.
AD  - 3 Faculty of Health and Biomedical Sciences, Symbiosis International University, 
      Pune, India.
FAU - Mishra, Ashwani Kumar
AU  - Mishra AK
AD  - 4 NDDTC and Department of Psychiatry, AIIMS, New Delhi, India.
FAU - Kumar, Anup
AU  - Kumar A
AD  - 5 Department of Urology, Safdarjung Hospital, New Delhi, India.
FAU - Vasudeva, Pawan
AU  - Vasudeva P
AD  - 5 Department of Urology, Safdarjung Hospital, New Delhi, India.
FAU - Mohanty, Nayan Kumar
AU  - Mohanty NK
AD  - 6 Department of Urology, Saket City Hospital, New Delhi, India.
FAU - Saxena, Sunita
AU  - Saxena S
AD  - 1 National Institute of Pathology (Indian Council of Medical Research), New
      Delhi, India.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental
      Biology and Medicine
JID - 8409922
RN  - 0 (Cytokines)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Cytokines/blood/*metabolism/urine
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Invasiveness
MH  - Neoplasm Recurrence, Local
MH  - Urinary Bladder Neoplasms/immunology/mortality/*pathology
OTO - NOTNLM
OT  - Immune response
OT  - bladder cancer
OT  - cytokines
OT  - non-invasive marker
EDAT- 2017/04/06 06:00
MHDA- 2017/04/11 06:00
CRDT- 2017/04/06 06:00
AID - 10.1177/1010428317697552 [doi]
PST - ppublish
SO  - Tumour Biol. 2017 Apr;39(4):1010428317697552. doi: 10.1177/1010428317697552.

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