Expression of choline kinase alpha to predict outcome in patients with early-stage non-small-cell lung cancer:: a retrospective study

Background Adequate prognostic markers to predict outcome of patients with lung cancer are still needed. The aim of this study was to assess whether choline kinase alpha (ChoK alpha) gene expression could identify patients with different prognoses. ChoKa is an enzyme involved in cell metabolism and proliferation and has a role in oncogene-mediated transformation in several human tumours, including lung cancer. Methods 60 patients with non-small-cell lung cancer (NSCLC) who had undergone surgical resection in a single Centre were enrolled into the study as the training group. We used real-time reverse-transcriptase PCR (RT-PCR) to measure ChoK alpha gene expression and analyse the association between ChoK alpha expression and survival in evaluable patients. Additionally, a second group of 120 patients with NSCLC from a different hospital were enrolled into the study as the validation group. We did an overall analysis of all 167 patients who had available tissue to confirm the cut-off point for future studies. The primary endpoints were hing-cancer-specific survival and relapse-free survival. Findings Seven of the 60 patients in the training group were not evaluable due to insufficient tissue. In the 53 evaluable patients, the cut-off for those with ChoKa overexpression was defined by receiver operator under the curve (ROC) methodology. 4-year lung-cancer-specific survival was 54-43% (95% CI 28.24-80.61) for 25 patients with ChoK alpha expression above the ROC-defined cut-off compared with 88.27% (75.79-100) for 28 patients with concentrations of the enzyme below this cut-off (hazard ratio [HR] 3.14 [0.83-11.88], p=0.07). In the validation group, six of the 120 enrolled patients were not evaluable due to insufficient tissue. For the other 114 patients, 4-year lung-cancer-specific survival was 46-66% (32.67-59.65) for those with ChoKa expression above the ROC-defined cut-off compared with 67.01% (50.92-81.11) for patients with concentrations of ChoKa below the cut-off (HR 1.87 [1-01-3.46], p=0.04). A global analysis of all 167 patients further confirmed the association between ChoK alpha overexpression. and worse clinical outcome of patients with NSCLC: 4-year lung-cancer-specific survival for ChoK alpha expression above the ROC-defined cut-off was 49.00% (36.61-60.38) compared with 70.52% (59.80-76.75) for those with concentrations of ChoKa below the cut-off (HR 1.98 [1.14-3.45], p=0.01). The overall analysis confirmed the cut-off for ChoK alpha expression should be 1.91-times higher than concentrations noted in healthy tissues when ChoK alpha is used as an independent predictive factor of relapse-free and hing-cancer-specific survival in patients with early-stage NSCLC. Interpretation ChoK alpha expression is a new prognostic factor that could be used to help identify patients with early-stage NSCLC who might be at high risk of recurrence, and to identify patients with favourable prognosis who could receive less aggressive treatment options or avoid adjuvant systemic treatment. New treatments that inhibit ChoK alpha expression or activity in patients with lung cancer should be studied further.