Circulating tumor M2 pyruvate kinase and thymidine kinase 1 are potential predictors for disease recurrence in renal cell carcinoma after nephrectomy.
OBJECTIVE
Pyruvate kinase type M2 (TuM2-PK) and thymidine kinase 1 (TK1) are the key enzymes involved in tumor cells metabolism and proliferation. We explored the association of their preoperative circulating levels with disease recurrence in patients with renal cell carcinoma (RCC).


METHODS
We measured the plasma levels of TuM2-PK levels and serum TK1 activity preoperatively in patients with RCC, using a quantitative ELISA, and correlated the results with clinicopathological parameters.


RESULTS
Significantly higher levels of TuM2-PK and TK1 were found in 116 patients with RCC compared with 20 healthy participants (P < .001 and P = .03), but not compared with 27 patients with benign kidney tumors (P = .13 and P = .72). There was a significant association between the level of TuM2-PK and of TK1 activity with T stage (P = .01 and P = .04). Of 2 markers only TuM2-PK was significantly associated with tumor grade (P = .001). The presence of extensive tumor necrosis (> 50%) was associated with high TuM2-PK (P = .001) and low TK1 (P = .03). The 5-year recurrence-free survival for patients with elevated TuM2-PK or TK1 was significantly lower compared with those for patients with normal marker levels (55% vs 94%, P < .001 and 21% vs 90%, P = .002). Multivariate Cox Proportional Hazard analysis demonstrated that TuM2-PK and TK1, adjusted for stage, grade and tumor necrosis were retained as independent predictors of disease recurrence (HR = 7.3, P = .04 and HR = 3.8, P = .03).


CONCLUSIONS
The measurements of 2 circulating biomarkers, TuM2-PK and TK1, in RCC patients before nephrectomy can be useful for predicting recurrence and stratifying the patients into risk groups for possible adjuvant treatment.
Nisman
Benjamin
B
Department of Oncology, Hadassah and Hebrew University Medical Centre, Jerusalem, Israel. nisman@hadassah.org.il
Yutkin
Vladimir
V
Nechushtan
Hovav
H
Gofrit
Ofer N
ON
Peretz
Tamar
T
Gronowitz
Simon
S
Pode
Dov
D
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000601:surgery*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000175:diagnosis*; D009392:Nephrectomy; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011770:Pyruvate Kinase / Q000097:blood*; D013937:Thymidine Kinase / Q000097:blood*
D014408:Biomarkers, Tumor; D013937:Thymidine Kinase; C092717:thymidine kinase 1; D011770:Pyruvate Kinase