Abstract
BackgroundLung cancer is the leading cause of cancer-related death worldwide. Currently, tumor, node, metastasis (TNM) staging provides the most accurate prognostic parameter for patients with non-small cell lung cancer (NSCLC). However, the overall survival of patients with resectable tumors varies significantly, indicating the need for additional prognostic factors to better predict the outcome of the disease, particularly within a given TNM subset.Methods and FindingsIn this study, we investigated whether adenocarcinomas and squamous cell carcinomas could be differentiated based on their global aberrant DNA methylation patterns. We performed restriction landmark genomic scanning on 40 patient samples and identified 47 DNA methylation targets that together could distinguish the two lung cancer subgroups. The protein expression of one of those targets, oligodendrocyte transcription factor 1 (OLIG1), significantly correlated with survival in NSCLC patients, as shown by univariate and multivariate analyses. Furthermore, the hazard ratio for patients negative for OLIG1 protein was significantly higher than the one for those patients expressing the protein, even at low levels.ConclusionsMultivariate analyses of our data confirmed that OLIG1 protein expression significantly correlates with overall survival in NSCLC patients, with a relative risk of 0.84 (95% confidence interval 0.77–0.91, p < 0.001) along with T and N stages, as indicated by a Cox proportional hazard model. Taken together, our results suggests that OLIG1 protein expression could be utilized as a novel prognostic factor, which could aid in deciding which NSCLC patients might benefit from more aggressive therapy. This is potentially of great significance, as the addition of postoperative adjuvant chemotherapy in T2N0 NSCLC patients is still controversial.
Highlights
Lung cancer is the leading cause of cancer-related death worldwide [1]
Multivariate analyses of our data confirmed that oligodendrocyte transcription factor 1 (OLIG1) protein expression significantly correlates with overall survival in non-small cell lung cancer (NSCLC) patients, with a relative risk of 0.84 (95% confidence interval 0.77–0.91, p, 0.001) along with T and N stages, as indicated by a Cox proportional hazard model
Our results suggests that OLIG1 protein expression could be utilized as a novel prognostic factor, which could aid in deciding which NSCLC patients might benefit from more aggressive therapy
Summary
Lung cancer is the leading cause of cancer-related death worldwide [1]. It is estimated that over 1.2 million people are diagnosed with lung cancer annually, and 1.1 million die from the disease [2]. The most accurate prognostic factor for patients with non-small cell lung cancer (NSCLC) is tumor, node, metastasis (TNM) clinico-pathologic staging [4]. Patients with early-stage lung cancer exhibit a wide spectrum of survival, indicating the need for additional prognostic parameters to better predict the outcome of the disease [5]. Much effort has been dedicated to identifying molecular markers that might improve the classification of NSCLC Such markers should give prognostic information, but could help identify patients that would benefit from novel therapeutic strategies or, alternatively, those for which additional treatment is not needed. Tumor, node, metastasis (TNM) staging provides the most accurate prognostic parameter for patients with non-small cell lung cancer (NSCLC). The overall survival of patients with resectable tumors varies significantly, indicating the need for additional prognostic factors to better predict the outcome of the disease, within a given TNM subset. About 70% of patients with stage I or II lung cancer, but only 2% of patients with stage IV lung cancer, survive for five years after diagnosis
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