Project description:Lung cancer is the leading cause of cancer deaths in the United States. Patients with early stage lung cancer have the best prognosis with surgical removal of the tumor, but the disease is often asymptomatic until advanced disease develops, and there are no effective blood-based screening methods for early detection of lung cancer in at-risk populations. We have explored the lipid profiles of blood plasma exosomes using ultra high-resolution Fourier transform mass spectrometry (UHR-FTMS) for early detection of the prevalent non-small cell lung cancers (NSCLC). Exosomes are nanovehicles released by various cells and tumor tissues to elicit important biofunctions such as immune modulation and tumor development. Plasma exosomal lipid profiles were acquired from 39 normal and 91 NSCLC subjects (44 early stage and 47 late stage). We have applied two multivariate statistical methods, Random Forest (RF) and Least Absolute Shrinkage and Selection Operator (LASSO) to classify the data. For the RF method, the Gini importance of the assigned lipids was calculated to select 16 lipids with top importance. Using the LASSO method, 7 features were selected based on a grouped LASSO penalty. The Area Under the Receiver Operating Characteristic curve for early and late stage cancer versus normal subjects using the selected lipid features was 0.85 and 0.88 for RF and 0.79 and 0.77 for LASSO, respectively. These results show the value of RF and LASSO for metabolomics data-based biomarker development, which provide robust an independent classifiers with sparse data sets. Application of LASSO and Random Forests identifies lipid features that successfully distinguish early stage lung cancer patient from healthy individuals.
Project description:Drug repositioning is a popular approach in the pharmaceutical industry for identifying potential new uses for existing drugs and accelerating the development time. Non-small-cell lung cancer (NSCLC) is one of the leading causes of death worldwide. To reduce the biological heterogeneity effects among different individuals, both normal and cancer tissues were taken from the same patient, hence allowing pairwise testing. By comparing early- and late-stage cancer patients, we can identify stage-specific NSCLC genes. Differentially expressed genes are clustered separately to form up- and downregulated communities that are used as queries to perform enrichment analysis. The results suggest that pathways for early- and late-stage cancers are different. Sets of up- and downregulated genes were submitted to the cMap web resource to identify potential drugs. To achieve high confidence drug prediction, multiple microarray experimental results were merged by performing meta-analysis. The results of a few drug findings are supported by MTT assay or clonogenic assay data. In conclusion, we have been able to assess the potential existing drugs to identify novel anticancer drugs, which may be helpful in drug repositioning discovery for NSCLC.
Project description:Local failure of non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT) often occurs within 2 years and delayed local failure is uncommon. In the present study, features of late local failure (LLF; >2 years after SBRT) after SBRT were investigated and compared with those of early local failure (ELF; ≤2 years after SBRT) to explore whether these two local recurrence features have different prognostic implications. Patients who underwent SBRT for stage I-IIA NSCLC between July 2006 and March 2014 were retrospectively reviewed. Overall, 173 patients underwent SBRT for NSCLC. The median follow-up times after SBRT were 50 and 31 months for survival and computed tomography (CT) follow-up, respectively. LLF and ELF occurred in 7 and 13 patients, respectively. The median times to LLF and ELF were 42 months (range, 31-61 months) and 13 months (range, 4-16 months), respectively. Local-only failure occurred in 14% (1/7) of LLF cases and 77% (10/13) of ELF cases, which was significantly different (Fisher's exact test, P=0.02). Curative-intent salvage treatment was impossible in all of the LLF cases and 69% (9/13) of the ELF cases, which was significantly different (Fisher's exact test, P<0.01). The median survival times after local failure were 9 and 25 months for patients with LLF and ELF, respectively. Additionally, the 1-year overall survival rates after local failure were 29 and 83% in the LLF and ELF groups, respectively, which was significantly different (log-rank test, P<0.01 at 1-year). In summary, the prognosis after LLF was significantly unfavorable compared with after ELF. Curative-intent salvage treatment is often difficult for LLF due to metastases. Therefore, it seems reasonable to decrease the frequency of follow-up CT for detecting tumor recurrence after the first 2 years post-SBRT.
Project description:Stereotactic body radiotherapy (SBRT) represents a consolidated treatment option for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). The clinical evidence accumulated in the past decade supports its use as an alternative to surgery with comparable survival outcomes. Due to its limited toxicity, SBRT is also applicable to elderly patients with very poor baseline pulmonary function or other severe comorbidities. Recent comparative studies in operable patients raised the issue of the possible use of SBRT also for this subgroup, with quite promising results that still should be fully confirmed by prospective trials with long-term follow-up. Aim of this review is to summarize and discuss the major studies conducted over the years on SBRT and to provide data on the efficacy and toxicity of this radiotherapy technique for stage I NSCLC. Technical aspects and quality of life related issues are also discussed, with the goal to provide information on the current role and limitations of SBRT in clinical practice.
Project description:BackgroundDespite of intense research in early cancer detection, there is a lack of biomarkers for the reliable detection of malignant tumors, including non-small cell lung cancer (NSCLC). DNA methylation changes are common and relatively stable in various types of cancers, and may be used as diagnostic or prognostic biomarkers.MethodsWe performed DNA methylation profiling of samples from 48 patients with stage I NSCLC and 18 matching cancer-free lung samples using microarrays that cover the promoter regions of more than 14,500 genes. We correlated DNA methylation changes with gene expression levels and performed survival analysis.ResultsWe observed hypermethylation of 496 CpGs in 379 genes and hypomethylation of 373 CpGs in 335 genes in NSCLC. Compared to adenocarcinoma samples, squamous cell carcinoma samples had 263 CpGs in 223 hypermethylated genes and 513 CpGs in 436 hypomethylated genes. 378 of 869 (43.5%) CpG sites discriminating the NSCLC and control samples showed an inverse correlation between CpG site methylation and gene expression levels. As a result of a survival analysis, we found 10 CpGs in 10 genes, in which the methylation level differs in different survival groups.ConclusionsWe have identified a set of genes with altered methylation in NSCLC and found that a minority of them showed an inverse correlation with gene expression levels. We also found a set of genes that associated with the survival of the patients. These newly-identified marker candidates for the molecular screening of NSCLC will need further analysis in order to determine their clinical utility.
Project description:Lymph node dissection is a vital part of surgical treatment in early-stage non-small cell lung cancer (NSCLC). Removal of metastatic lymph nodes while preservation of intact lymph nodes are equally important. For hospitalized early-stage patients with limited lymph node metastasis, the operation treatment should be made according to some rules such as lobe-specific lymph node drainage pattern. In order to prevent unnecessary surgical trauma in early-stage patients, a minimally invasive approach with selective lymph node excision is preferred for more clinical benefits. This review summarizes the existing findings on lobe-specific lymph node drainage pattern and we hope to provide guidance for selective lymph node dissection (SLND). Furthermore, we include information on histologic views, a tumor marker and protocols of SLND, with hope to inspire creative research and clinical trials in this field.
Project description:We are investigating the molecular development of squamous cell lung carcinoma based upon analysis of global gene expression profiles representing progressive stages of cancer development, consisting of precancerous, carcinoma-in-situ, and invasive cancer. Keywords: global gene expression analysis, lung cancer development In this study, we have generated 13 SAGE libraries, consisting of five carcinoma-in-situ libraries, six early invasive squamous cell carcinoma libraries, and two reference libraries representing precancerous squamous development.
Project description:The management of advanced non-small cell lung cancer (NSCLC) has been revolutionized in recent years with the introduction of biomarker-targeted molecular therapies and immune checkpoint inhibitors. In contrast, since adjuvant chemotherapy was first established twenty years ago as the standard of care, little has changed for resected early-stage (IB-IIIA) patients for whom the potential for cure is greatest. In this manuscript we will review recently presented data as well as ongoing/planned studies in this arena. So far, investigative efforts have yielded mixed results regarding the use of tyrosine kinase inhibitors (TKIs) in early-stage NSCLC, though a series of now better planned, biomarker-driven ongoing phase III trials may be more informative. Several innovative immunotherapy studies have already shown promising results principally in the neoadjuvant setting with a large number of pivotal neo-adjuvant and adjuvant trials now in progress. Given the more robust design and biomarker-focused approach of the new generation of studies, significant advances in the optimal curative treatment of early stage NSCLC are anticipated.
Project description:Lung cancer is the most common cancer and the leading cause of cancer death in the world, among which non-small cell lung cancer (NSCLC) accounts for about 85% of the total lung cancer. With the widespread of computed tomography (CT) and other imaging screening methods, the pathological types of lung cancer have changed from central squamous cell carcinoma to the early-stage lung adenocarcinoma, which is manifested as isolated pulmonary nodules and ground glass nodules on CT. Early diagnosis and treatment of lung cancer is of crucial clinical significance, and the continuous development and improvement of minimally invasive interventional techniques provide more options for lung cancer treatment, such as stereotactic radiation, percutaneous ablation, and bronchial intervention. This paper will make a review on the principle, advantages, disadvantages and prospects of minimally invasive interventional therapy commonly used in clinical practice.