Prognostic and Predictive Values of Subcellular Localisation of RET in Renal Clear-Cell Carcinoma.
Metastatic renal cell carcinoma (RCC) presents a poor prognosis and an unpredictable course. To date, no validated biomarkers can predict the outcome of RCC. Ongoing efforts are conducted to identify the molecular markers of RCC progression, as well as the targets for novel therapeutic approaches. RET is a tyrosine kinase receptor which has been investigated as a possible target in other cancers because it is involved in oncogenic activation. To evaluate the predictive and prognostic functions of RET in ccRCC, a tissue microarray study was conducted on 273 ccRCC patients. Results showed that both RET cytoplasmic and nuclear expression were independently associated with PFS and OS, and the combined RET cytoplasmic and nuclear statuses demonstrated that the ratio of high nuclear RET and cytoplasmic RET was the strongest predictor of both PFS and OS. The high cytoplasmic RET expression retained its independent poor prognostic value in targeted drug treated patients. The RET nuclear expression was associated with distant metastasis. Moreover, the RET nuclear expression was an independent predictor of ccRCC postoperative metastasis. In conclusion, RET may be useful in prognostication and can be used at initial diagnosis to identify patients with high potential to develop metastasis.
Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Medical Academy, Beijing 100853, China.
Lei
L
Wang
Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Medical Academy, Beijing 100853, China.
Yu
Y
Zhang
Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Medical Academy, Beijing 100853, China.
Yu
Y
Gao
Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Medical Academy, Beijing 100853, China.
Yang
Y
Fan
Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Medical Academy, Beijing 100853, China.
Luyao
L
Chen
Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Medical Academy, Beijing 100853, China.
Kan
K
Liu
Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Medical Academy, Beijing 100853, China.
Qingyu
Q
Meng
Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Medical Academy, Beijing 100853, China.
Chaofei
C
Zhao
Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Medical Academy, Beijing 100853, China.
Xin
X
Ma
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D051096:Proto-Oncogene Proteins c-ret / Q000378:metabolism*; D016019:Survival Analysis; D046888:Tissue Array Analysis; D055815:Young Adult
D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human