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CHKA mediates the poor prognosis of lung adenocarcinoma and acts as a prognostic indicator

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ABSTRACT

Choline kinase α (CHKA), the enzyme that converts choline to phosphocholine, has been studied in human carcinogenesis widely. However, the expression and underlying clinicopathological characteristics of CHKA in lung adenocarcinoma remains elusive. In the present study, a tissue microarray of 119 pairs of lung adenocarcinoma samples and corresponding adjacent normal mucosae was used to analysis CHKA expression by immunohistochemistry, and CHKA was observed to exhibit enhanced expression in lung adenocarcinoma tissues. Elevated CHKA expression in lung adenocarcinoma tissues at the gene and protein level was observed. The levels of CHKA expression were closely associated with the poor prognosis status of lung adenocarcinoma patients. Furthermore, certain clinicopathological characteristics such as tumor diameter and differentiation were observed to be significant in those lung adenocarcinoma patients who displayed enhanced CHKA expression. The analysis of CHKA expression could provide a more precise way to predict the prognosis of lung adenocarcinoma patients. Collectively, the present study revealed a novel biomarker in lung adenocarcinoma, and indicated that CHKA may be a promising prognostic marker and therapeutic target for lung adenocarcinoma.

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Clinical Significance of CHKA expression in lung adenocarcinoma. (A) Lung adenocarcinoma patients were divided into a CHKA ‘high’ group (whose fold-change of relative expression was higher than the median) and ‘low’ group (whose fold-change of relative expression was lower than the median), and the overall survival rates of the 119 lung adenocarcinoma patients were compared between the CHKA ‘high’ group and the CHKA ‘low’ group. (B) Multivariate analysis of hazard ratios for overall survival of lung adenocarcinoma patients in tissue microarray. (C) Comparison of CHKA expression between lung adenocarcinoma patients whose differentiation status is poor or well. *P<0.05. Patients with poor differentiation exhibited higher CHKA expression than those with well-differentiated tumors. Cum, cumulative; CHKA, choline kinase α; HR, hazard ratio; CI, confidence interval; IHC, immunohistochemistry.
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f2-ol-0-0-4810: Clinical Significance of CHKA expression in lung adenocarcinoma. (A) Lung adenocarcinoma patients were divided into a CHKA ‘high’ group (whose fold-change of relative expression was higher than the median) and ‘low’ group (whose fold-change of relative expression was lower than the median), and the overall survival rates of the 119 lung adenocarcinoma patients were compared between the CHKA ‘high’ group and the CHKA ‘low’ group. (B) Multivariate analysis of hazard ratios for overall survival of lung adenocarcinoma patients in tissue microarray. (C) Comparison of CHKA expression between lung adenocarcinoma patients whose differentiation status is poor or well. *P<0.05. Patients with poor differentiation exhibited higher CHKA expression than those with well-differentiated tumors. Cum, cumulative; CHKA, choline kinase α; HR, hazard ratio; CI, confidence interval; IHC, immunohistochemistry.

Mentions: The clinical implication of CHKA expression in lung adenocarcinoma was analyzed. High levels of CHKA were observed to be associated with poor survival in lung adenocarcinoma patients (Fig. 2A). The association between CHKA expression in tumor tissues and the clinicopathological characteristics of the 119 patients was examined (Table II). Correlation regression analysis indicated that prognosis was correlated with several individual parameters, including CHKA expression, tumor diameter, tumor stage and differentiation (Table III). These individual parameters were further analyzed with a multivariate Cox proportional hazards model. The results indicated that CHKA expression, tumor diameter and differentiation were significant and independent factors that affected the survival of lung adenocarcinoma patients (Table III and Fig. 2B). Among these factors, the significant hazard ratio (HR) value for the cumulative survival of CHKA expression levels was 2.644 [95% confidence interval (CI), 1.217–5.746; P=0.05]. Tumor diameter and differentiation also exhibited a significant HR value for cumulative survival. For tumor diameter, the HR value was determined to be 2.462 (95% CI, 1.249–4.853; P=0.01). Poor differentiation displayed the greatest HR value (HR, 2.644; 95% CI, 1.217–5.746; P=0.01). Since poor differentiated lung cancer exhibited the greatest HR value for cumulative survival, the expression level of CHKA in poor- vs. well-differentiated cancer was further analyzed. Patients with poor differentiation tended to have high CHKA expression levels (Fig. 2C). As known, lung cancer patients with poor differentiation are more inclined to bad prognosis compared with high differentiation group (9); therefore, this result suggested that CHKA may act as an oncogene and mediate the poor prognosis and poor differentiation of lung cancer.


CHKA mediates the poor prognosis of lung adenocarcinoma and acts as a prognostic indicator
Clinical Significance of CHKA expression in lung adenocarcinoma. (A) Lung adenocarcinoma patients were divided into a CHKA ‘high’ group (whose fold-change of relative expression was higher than the median) and ‘low’ group (whose fold-change of relative expression was lower than the median), and the overall survival rates of the 119 lung adenocarcinoma patients were compared between the CHKA ‘high’ group and the CHKA ‘low’ group. (B) Multivariate analysis of hazard ratios for overall survival of lung adenocarcinoma patients in tissue microarray. (C) Comparison of CHKA expression between lung adenocarcinoma patients whose differentiation status is poor or well. *P<0.05. Patients with poor differentiation exhibited higher CHKA expression than those with well-differentiated tumors. Cum, cumulative; CHKA, choline kinase α; HR, hazard ratio; CI, confidence interval; IHC, immunohistochemistry.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4998128&req=5

f2-ol-0-0-4810: Clinical Significance of CHKA expression in lung adenocarcinoma. (A) Lung adenocarcinoma patients were divided into a CHKA ‘high’ group (whose fold-change of relative expression was higher than the median) and ‘low’ group (whose fold-change of relative expression was lower than the median), and the overall survival rates of the 119 lung adenocarcinoma patients were compared between the CHKA ‘high’ group and the CHKA ‘low’ group. (B) Multivariate analysis of hazard ratios for overall survival of lung adenocarcinoma patients in tissue microarray. (C) Comparison of CHKA expression between lung adenocarcinoma patients whose differentiation status is poor or well. *P<0.05. Patients with poor differentiation exhibited higher CHKA expression than those with well-differentiated tumors. Cum, cumulative; CHKA, choline kinase α; HR, hazard ratio; CI, confidence interval; IHC, immunohistochemistry.
Mentions: The clinical implication of CHKA expression in lung adenocarcinoma was analyzed. High levels of CHKA were observed to be associated with poor survival in lung adenocarcinoma patients (Fig. 2A). The association between CHKA expression in tumor tissues and the clinicopathological characteristics of the 119 patients was examined (Table II). Correlation regression analysis indicated that prognosis was correlated with several individual parameters, including CHKA expression, tumor diameter, tumor stage and differentiation (Table III). These individual parameters were further analyzed with a multivariate Cox proportional hazards model. The results indicated that CHKA expression, tumor diameter and differentiation were significant and independent factors that affected the survival of lung adenocarcinoma patients (Table III and Fig. 2B). Among these factors, the significant hazard ratio (HR) value for the cumulative survival of CHKA expression levels was 2.644 [95% confidence interval (CI), 1.217–5.746; P=0.05]. Tumor diameter and differentiation also exhibited a significant HR value for cumulative survival. For tumor diameter, the HR value was determined to be 2.462 (95% CI, 1.249–4.853; P=0.01). Poor differentiation displayed the greatest HR value (HR, 2.644; 95% CI, 1.217–5.746; P=0.01). Since poor differentiated lung cancer exhibited the greatest HR value for cumulative survival, the expression level of CHKA in poor- vs. well-differentiated cancer was further analyzed. Patients with poor differentiation tended to have high CHKA expression levels (Fig. 2C). As known, lung cancer patients with poor differentiation are more inclined to bad prognosis compared with high differentiation group (9); therefore, this result suggested that CHKA may act as an oncogene and mediate the poor prognosis and poor differentiation of lung cancer.

View Article: PubMed Central - PubMed

ABSTRACT

Choline kinase &alpha; (CHKA), the enzyme that converts choline to phosphocholine, has been studied in human carcinogenesis widely. However, the expression and underlying clinicopathological characteristics of CHKA in lung adenocarcinoma remains elusive. In the present study, a tissue microarray of 119 pairs of lung adenocarcinoma samples and corresponding adjacent normal mucosae was used to analysis CHKA expression by immunohistochemistry, and CHKA was observed to exhibit enhanced expression in lung adenocarcinoma tissues. Elevated CHKA expression in lung adenocarcinoma tissues at the gene and protein level was observed. The levels of CHKA expression were closely associated with the poor prognosis status of lung adenocarcinoma patients. Furthermore, certain clinicopathological characteristics such as tumor diameter and differentiation were observed to be significant in those lung adenocarcinoma patients who displayed enhanced CHKA expression. The analysis of CHKA expression could provide a more precise way to predict the prognosis of lung adenocarcinoma patients. Collectively, the present study revealed a novel biomarker in lung adenocarcinoma, and indicated that CHKA may be a promising prognostic marker and therapeutic target for lung adenocarcinoma.

No MeSH data available.


Related in: MedlinePlus