Poor outcome in primary non-small cell lung cancers is predicted by transketolase TKTL1 expression

Aim: Malignant tumours ferment glucose to lactate even in the presence of sufficient oxygen (the Warburg effect). Transketolases seem to be involved in this metabolic switch. TKTL1 has previously been shown to encode a transketolase-like enzyme which is overexpressed in colon, urothelial and breast cancer. Here we investigated the prognostic impact of TKTL1 expression in non-small cell lung cancer (NSCLC). Methods: Curatively operated NSCLCs of 201 patients were analysed for TKTL1 expression by immunohistochemistry (clone JFC12T10). Statistical analyses with regard to clinicopathological parameters included Kaplan-Meier and multivariate Cox regression analyses. Results: There was no or mild TKTL1 expression in 89 tumours (44.7%), whereas in 110 tumours (55.3%) TKTL1 was overexpressed. TKTL1 overexpression correlated with tumour-type (p = 0.02) and histological grading (p = 0.033) and was significantly associated with poor patient survival (p = 0.008). In addition, TKTL1 overexpression identified patients with poor clinical outcome among lymph node negative (p = 0.039) and well to moderately differentiated (p = 0.005) NSCLCs; furthermore, it proved to be an independent prognostic factor (p = 0.0252). Conclusion: Our data suggest that TKTL1 overexpression is a new and independent predictor of survival for patients with NSCLC. Since inhibition of transketolase enzyme reactions has recently been shown to effectively suppress tumour growth, TKTL1 represents a novel pharmacodiagnostic marker.