Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: a retrospective study.
BACKGROUND
Distant metastasis is the main cause of death from renal-cell carcinoma, and the metastatic potential of tumours is often unpredictable. We aimed to investigate whether IMP3, an oncofetal RNA-binding protein, can be used as a biomarker to predict metastasis and prognosis of renal-cell carcinoma.


METHODS
We studied 501 primary and metastatic renal-cell tumours. 371 patients with localised primary tumours were further investigated by use of survival analysis. We assessed IMP3 expression in tumour tissues by immunohistochemistry, and IMP3 mRNA and protein expression in selected tissues by quantitative real-time PCR and western blot analysis.


RESULTS
Compared with non-metastatic renal-cell tumours, IMP3 expression was greatly increased not only in metastatic tumours but also in a subset of primary tumours that were likely to subsequently develop metastases. Patients with primary localised tumours that did not express IMP3 had a longer metastasis-free survival and overall survival than did those with tumours expressing IMP3 (p<0.0001). Patients with IMP3-positive localised tumours had a much lower 5-year metastasis-free survival than did those with IMP3-negative tumours (for stage I tumours, 44% vs 98%, hazard ratio 17.18 [95% CI 7.82-37.78]; stage II, 41% vs 94%, 10.14 [3.46-29.68]; stage III, 16% vs 62%, 4.04 [2.23-7.31]). IMP3 expression was also associated with reduced 5-year overall survival (stage I, 32% vs 89%, 6.44 [3.63-11.42]; stage II, 41% vs 88%, 6.93 [2.63-18.27]; stage III, 14% vs 58%, 3.46 [1.98-6.05]). Multivariable analysis of IMP3 status (positive vs negative) in primary tumours showed hazard ratios of 5.84 (95% CI 3.60-9.49) for metastasis-free survival and 4.01 (2.66-6.05) for overall survival (both p<0.0001), which were much higher than hazard ratios associated with other independent risk factors.


CONCLUSIONS
IMP3 is an independent prognostic marker that can be used at initial diagnosis of renal-cell carcinoma to identify patients who have a high potential to develop metastasis and who might benefit from early systemic treatment.
Jiang
Zhong
Z
University of Massachusetts Medical Center, Department of Pathology, Worcester, MA, USA. jiangz@ummhc.org
Chu
Peigou G
PG
Woda
Bruce A
BA
Rock
Kenneth L
KL
Liu
Qin
Q
Hsieh
Chung-Cheng
CC
Li
Cuizhen
C
Chen
Wengang
W
Duan
Hai Ou
HO
McDougal
Scott
S
Wu
Chin-Lee
CL
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000401:mortality / Q000556:secondary*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate
D014408:Biomarkers, Tumor; C498780:IGF2BP3 protein, human; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins