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

Translational Oncology Unit, CSIC-UAM-La Paz, National Center of Biotechnology, Madrid, Spain.
The Lancet Oncology (Impact Factor: 24.69). 11/2007; 8(10):889-97. DOI: 10.1016/S1470-2045(07)70279-6
Source: PubMed


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 (ChoKalpha) gene expression could identify patients with different prognoses. ChoKalpha is an enzyme involved in cell metabolism and proliferation and has a role in oncogene-mediated transformation in several human tumours, including lung cancer.
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 ChoKalpha gene expression and analyse the association between ChoKalpha 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 lung-cancer-specific survival and relapse-free survival.
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 ChoKalpha 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 ChoKalpha 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 ChoKalpha expression above the ROC-defined cut-off compared with 67.01% (50.92-81.11) for patients with concentrations of ChoKalpha 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 ChoKalpha overexpression and worse clinical outcome of patients with NSCLC: 4-year lung-cancer-specific survival for ChoKalpha 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 ChoKalpha below the cut-off (HR 1.98 [1.14-3.45], p=0.01). The overall analysis confirmed the cut-off for ChoKalpha expression should be 1.91-times higher than concentrations noted in healthy tissues when ChoKalpha is used as an independent predictive factor of relapse-free and lung-cancer-specific survival in patients with early-stage NSCLC.
ChoKalpha 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 ChoKalpha expression or activity in patients with lung cancer should be studied further.

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    • "While not all hepatomas demonstrate hyperglycolysis, tumor glycolytic activity in HCC has been correlated with HK2 expression in tumors and the risk of cancer recurrence [14]–[17]. Less is currently known about the role of choline metabolism in HCC, although there is increasing evidence supporting the prognostic relevance of CKA expression in other cancers [18]–[20]. To investigate HK2 and CKA expression as potential clinicopathologic variables in HCC, we assembled a microscopy array composed of HCC specimens from an institutional tumor tissue repository to allow tumor HK2 and CKA protein expression to be examined in tandem and in relation to clinicopathologic and survival data obtained from National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program member registries. "
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    PLoS ONE 10/2012; 7(10):e46591. DOI:10.1371/journal.pone.0046591 · 3.23 Impact Factor
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    • "Recent studies on the biological function of ChoK isozymes revealed that ChoKa may play a more prominent role in cancer development as compared to ChoKb, as only ChoKa was upregulated in breast cancer cell lines [9] and specific depletion of the ChoKa isoform by shRNA selectively induced apoptosis in several tumor-derived cell lines without affecting the viability of normal primary cells [10]. The ChoKa isoform has also been proposed as a new prognostic marker for predicting the clinical outcome in patients with non-small-cell lung cancer [11]. These observations have resulted in the development of an antitumoral strategy focused on ChoK inhibition. "
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    • "Based on the emerging evidences that specifically link CKα to the pathogenesis and prognosis of various cancers [15], [16], [29], [30], it is apparent that more focus should be given to the detection of this isoform. Our antibody provides the opportunity to study the regulation of both CKα1 and α2 expression in different cells and tissues through direct quantitative comparison of the expressed protein pattern. "
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    PLoS ONE 09/2010; 5(9):e12999. DOI:10.1371/journal.pone.0012999 · 3.23 Impact Factor
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