Abstract
To detect expression of hypoxia inducible factor-1α (HIF-1α) and lysyl oxidase (LOX) in non-small cell lung cancer (NSCLC) and explore their roles in prognosis. The mRNA levels of HIF-1α and LOX were investigated by real-time reverse-transcriptase polymerase chain reaction in 40 cases of tumour and paired normal tissues. In addition, protein expression of HIF-1α and LOX was examined by immunohistochemistry in 82 cases of tumour and 45 paired normal tissues. The relationship between HIF-1α or LOX and clinicopathologic characteristics, as well as the correlation between HIF-1α and LOX, were also examined. Kaplan-Meier survival curves and the log-rank test were used to analyze progression-free survival. HIF-1α or LOX mRNA levels in tumor tissues was significantly higher than those in paired normal tissues (p<0.01). Positive HIF-1α or LOX protein expression in tumor tissues was noted in 46/82 (56.1%) and 49/82 (59.8%) of the cases, respectively, being significantly higher than those in paired normal tissues (p<0.05). There was significant correlation between the expression of HIF-1α or LOX and tumor size, lymph node metastasis and pathological stage (p<0.05). The expression of HIF-1α and LOX had a significant inverse impact on survival of patients with NSCLC. HIF-1α and LOX may play a pivotal role in the development of NSCLC, and may act in synergy to promote the progression of NSCLC.
Highlights
Lung cancer is the leading cause of cancer death worldwide (Siegel et al, 2011)
non-small cell lung cancer (NSCLC) is still one of the most common carcinoma characterized by a high incidence of early recurrence and poor prognosis
With the development of molecular biology, the identification of reliable biomarkers for the early diagnosis, treatment and prognostic assessment would represent an important step in the clinical management of NSCLC
Summary
Lung cancer is the leading cause of cancer death worldwide (Siegel et al, 2011). Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. The relevance of HIF-1α on the prognosis in NSCLC has been investigated, conflicting results have been reported from different laboratories (Volm et al, 2000; Hirami et al, 2004; Swinson et al., 2004; Hung et al, 2009; Park et al, 2011). This suggests that the application of HIF-1α alone as an independent predictor of prognosis might be invalid, and in combination with other tumor markers should be considered. The formation of collagens or elastin cross-links leads to an increase in structural integrity and tensile strength, which play an important role in normal connective tissue function and embryonic development (Payne et al, 2007). The association between HIF-1α and LOX, and impact of their expression on NSCLC patients’ survival were analyzed
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