Purpose: Kinase insert domain-containing receptor (KDR) is one of the molecular targets used in cancer therapy. We studied the KDR expression characteristics and the relationship with the clinical parameters of the patients with lung cancer, to give the basic evidence and clue for tailoring therapy.
Methods: Reverse transcriptase and real-time PCR were used to evaluate the KDR mRNA expression levels in 222 tissue samples (106 tumor tissues, 106 matched normal tissues obtained from the same patients with lung cancer, and 10 normal lung specimens from individuals without lung cancer). The KDR mRNA expression level and clinical parameters were analyzed by paired-sample t test, ANOVA and linear regression, respectively. The Kaplan-Meier method and the log-rank test were used for survival analysis. Expression of KDR protein was also examined immunohistochemically in 15 tumor samples and 15 matched normal lung specimens.
Results: The KDR mRNA expression levels were significantly higher in normal tissues (mean 4.50 +/- 0.51) than that in the carcinoma tissues (mean 4.12 +/- 0.50, P < 0.0005). KDR expression in tumor tissues is associated with the histological status, tumor stage, cigarette smoking, and N stage of the patients with lung cancer (P < 0.05) analyzed by using ANOVA methods. Multivariate analysis showed that tumor stages and cigarette smoking status were the two most important independent predictors for the KDR expression levels in tumor tissues (R = 0.415, R (2) = 0.172, F = 10.694, P < 0.0005). Tumors with KDR mRNA expression levels above the mean had a shorter survival (466 +/- 313 days) than did patients with KDR expression levels below the mean (671 +/- 264 days), whereas Kaplan-Meier analysis and log-rank test showed no significant difference in the overall survival between the patients (P = 0.2055). All the 15 normal lung tissues detected showed scale 2 KDR immunostaining. The intensity of immunostaining for KDR in tumor specimens varied from negative (scale 0) to strongest (scale 3) staining.
Conclusions: Locally advanced and non-cigarette smoking patients with lung cancer may be the two valuable surrogate markers for KDR mRNA higher levels. Non-squamous lung cancer, N 2 stage may be the secondary markers for that. The KDR expression level in normal lung tissue is stable, but varied in tumor tissues. Targeting KDR therapy in lung cancer might considerate these clinical and KDR expression information. Further confirmation study must be needed.