Abstract
The high mortality rate of lung cancer patients is mainly due to the late stage at which lung cancer is diagnosed. For effective cancer prevention programs and early diagnosis, better blood-based markers are needed. Hence, blood-based microarray profiling of microRNA (miR) expression was performed in preoperative serum of 21 non-small cell lung cancer (NSCLC) patients and 11 healthy individuals by microfluid biochips containing 1158 different miRs. Two out of the 30 most dysregulated miRs were further validated in serum of 97 NSCLC patients, 20 patients with benign lung diseases and 30 healthy individuals by TaqMan MicroRNA Assays. Microarray profiling showed that miR-361-3p and miR-625* were significantly down-regulated in serum of lung cancer patients. Their further evaluation by quantitative RT-PCR showed that the levels of miR-361-3p and miR-625* were lower in NSCLC than in benign disease (p = 0.0001) and healthy individuals (p = 0.0001, p = 0.0005, respectively). Moreover, the levels of miR-625* were significantly lower in patients with large cell lung cancer (LCLC, p = 0.014) and smoking patients (p = 0.030) than in patients with adenocarcinoma and non-smoking patients, respectively. A rise in the levels of both miRs was observed in the postoperative samples compared with the preoperative levels (p = 0.0001). Functional analyses showed that Smad2 and TGFß1 are not dysregulated by miR-361-3p and miR-625* in the lung cell line A549, respectively. Our present pilot study suggests that miR-361-3p and miR-625* might have a protective influence on the development of NSCLC, and the quantitative assessment of these miRs in blood serum might have diagnostic potential to detect NSCLC, in particular in smokers.
Highlights
Worldwide, lung cancer is the leading cause of cancer-related death
1158 different miRs were used to quantify the expression of miRs in serum of 21 non-small cell lung cancer (NSCLC) patients and 11 healthy individuals
Dysregulated miRs were detected by the highest absolute value of logarithmized fold changes in comparison of NSCLC patients to healthy individuals
Summary
Lung cancer is the leading cause of cancer-related death. The carcinoma develops in four major histological types comprising squamous cell lung cancer (SQCLC), adenocarcinoma (ADC) and large cell lung cancer (LCLC) of non-small cell lung cancer (NSCLC), and small cell lung cancer (SCLC) [1]. In the majority of cases the patients develop NSCLC which is associated with an overall 5-year survival of only 15% and a high rate of tumor recurrence [2]. Lung cancer may be caused by exposures to etiologic agents, such as asbestos and cigarette smoke, and by advanced age [3]. Not all patients with lung cancer have an operable tumor. The current therapeutic strategies for lung cancer include combinations of cytotoxic chemotherapy and targeted biological therapies, such as bevacizumab and erlotinib [4]. Tomography-based population screenings for identifying high-risk individuals are carried out, minimally invasive biomarkers allowing repeated blood withdrawals are urgently needed to detect lung cancer early and personalize care of the patients [5]
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