Kallikrein-related peptidase 13: an independent indicator of favorable prognosis for patients with nonsmall cell lung cancer
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The KLK13 gene is dysregulated in several carcinomas, and its expression levels seem to be associated with disease prognosis. The aim of our study was to investigate the prognostic potential of KLK13 mRNA expression for patients with nonsmall cell lung cancer (NSCLC). Total RNA was isolated from cancerous and normal tissues from a cohort of 128 NSCLC patients. The KLK13 mRNA transcription levels were measured using a sensitive quantitative RT-PCR method. The results were normalized by dividing the KLK13 mRNA values with the geometric mean of mRNA expression from four reference genes: beta-actin, TATA-binding protein, hypoxanthine phosphoribosyltransferase 1, and acidic ribosomal phosphoprotein P0. The malignant tissues from the majority of patients (59.3 %) contained significantly more KLK13 mRNA transcripts than did the paired nonmalignant tissues (median difference 11.1-fold, P = 0.008). KLK13 was expressed at higher levels in females than that in males (P = 0.021). No other statistically significant association with clinicopathological data was observed. Kaplan-Meier survival analyses demonstrated that patients with KLK13-positive tumors survived significantly longer than those with KLK13-negative ones (P = 0.009). KLK13 expression was also shown to be able to stratify high-risk individuals among patients with early disease stages (P = 0.030). Multivariate Cox regression analysis showed that KLK13 expression is a favorable, independent prognostic indicator of overall survival (OS) (P = 0.024). Our results suggest that KLK13 mRNA expression constitutes a novel biomarker for the prediction of overall survival in NSCLC and that its quantitative assessment in tumor tissues can aid in treatment decision making.
KeywordsLung cancer Tissue kallikrein Biomarker Prognosis
Nonsmall cell lung cancer
Postsurgical pathologic tumor node metastasis
Squamous cell carcinoma
Oral squamous cell carcinoma
The English text was edited by Dr. Owen Parkes. We thank Prof. Pascal Dumont (Tours Hospital) and Lysiane Brick, Géraldine Meunier, Alexandra Fayault, and Aliette Decock-Giraudaud (CIC INSERM 202) for their help in collecting tissues and clinical data. This work was supported by funds from the Ligue Contre le Cancer (Comités d’Indre et Loire, du Morbihan et de la Sarthe).
Conflicts of interest
- 21.Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002;3(7):RESEARCH0034Google Scholar
- 33.Batevik R, Grong K, Segadal L, Stangeland L. The female gender has a positive effect on survival independent of background life expectancy following surgical resection of primary non-small cell lung cancer: a study of absolute and relative survival over 15 years. Lung Cancer. 2005;47(2):173–81.CrossRefPubMedGoogle Scholar
- 36.Wu JY, Wang J, Lai JC, Cheng YW, Yeh KT, Wu TC, et al. Association of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with p53 mutation occurrence in non-small cell lung cancer with different histology, gender, and smoking status. Ann Surg Oncol. 2008;15(11):3272–7.CrossRefPubMedGoogle Scholar