Main Types Of Lung Cancer Research Articles

Identification and Validation of Two Lung Adenocarcinoma-Development Characteristic Gene Sets for Diagnosing Lung Adenocarcinoma and Predicting Prognosis.

Background: Lung adenocarcinoma (LUAD) is one of the main types of lung cancer. Because of its low early diagnosis rate, poor late prognosis, and high mortality, it is of great significance to find biomarkers for diagnosis and prognosis.Methods: Five hundred and twelve LUADs from The Cancer Genome Atlas were used for differential expression analysis and short time-series expression miner (STEM) analysis to identify the LUAD-development characteristic genes. Survival analysis was used to identify the LUAD-unfavorable genes and LUAD-favorable genes. Gene set variation analysis (GSVA) was used to score individual samples against the two gene sets. Receiver operating characteristic (ROC) curve analysis and univariate and multivariate Cox regression analysis were used to explore the diagnostic and prognostic ability of the two GSVA score systems. Two independent data sets from Gene Expression Omnibus (GEO) were used for verifying the results. Functional enrichment analysis was used to explore the potential biological functions of LUAD-unfavorable genes.Results: With the development of LUAD, 185 differentially expressed genes (DEGs) were gradually upregulated, of which 84 genes were associated with LUAD survival and named as LUAD-unfavorable gene set. While 237 DEGs were gradually downregulated, of which 39 genes were associated with LUAD survival and named as LUAD-favorable gene set. ROC curve analysis and univariate/multivariate Cox proportional hazards analyses indicated both of LUAD-unfavorable GSVA score and LUAD-favorable GSVA score were a biomarker of LUAD. Moreover, both of these two GSVA score systems were an independent factor for LUAD prognosis. The LUAD-unfavorable genes were significantly involved in p53 signaling pathway, Oocyte meiosis, and Cell cycle.Conclusion: We identified and validated two LUAD-development characteristic gene sets that not only have diagnostic value but also prognostic value. It may provide new insight for further research on LUAD.

A Survey on Multistage lung cancer Detection and Classification

Earlier, Lung cancer is the primary cause of cancer deaths worldwide among both men and women, with more than 1 million deaths annually. Lung Cancer have been widest difficulty faced by humans over recent couple of decades. When a person has lung cancer, they have abnormal cells that cluster together to form a tumor. A cancerous tumor is a group of cancer cells that can grow into and destroy nearby tissue. It can also spread to other parts of the body. There are two main types of lung cancer:1. Non-small cell lung cancer, 2. Small cell lung cancer. Non- small cell lung cancer has four main stages. In this research we are classifying four stages of lung cancer. Lung cancer detection at early stage has become very important. Currently many techniques are used based on image processing and deep learning techniques for lung cancer classification. For that lung patient Computer Tomography (CT) scan images are used to detect and lung nodules and classify lung cancer stage of that nodules. In this re- search we compare different Machine learning (SVM, KNN, RF etc.) techniques with deep learning (CNN, CDNN) techniques using different parameters accuracy, precision and recall. In this Research paper we com- pare all existing approach and find our better result for future application.

Computational virtual screening and structure-based design of some epidermal growth factor receptor inhibitors

BackgroundThe foremost cause of cancer mortality worldwide was lung cancer. Lung cancer is divided into small cell lung cancer and non-small cell lung cancer (NSCLC). The latter is the main type of lung cancer that account for about 90% of the cancer issues and estimate about 25% of the cancer mortality each year in the world. Among the types of lung cancer with about 1.5 million patients and less than 20% survival rate is NSCLC. Overexpression of EGFR tyrosine kinase was recognized to be the cause of NSCLC. Therefore, there is a need to develop more EGFR inhibitors due to drug-resistance development by the mutation.ResultComputational virtual screening on some epidermal growth factor receptor inhibitors (EGFRL858R/T790M inhibitors or NSCLC therapeutic agents) against their target protein (EGFR tyrosine kinase receptor pdb entry 3IKA) was performed via molecular docking simulation and pharmacokinetics to identify hit compounds with a promising affinity toward their target. The hit compounds discovered were compound 22 with −9.8 kcal/mol, 24 with −9.7 kcal/mol, 17 with −9.7 kcal/mol, and 19 with −9.5 kcal/mol respectively. These lead compounds were further subjected to drug-likeness and ADME prediction and found to be orally bioavailable. Six (6) new EGFRL858R/T790M inhibitors using compound 22 with the highest binding affinity as a template were designed.ConclusionThe six newly EGFRL858R/T790M inhibitors were found to have a better binding affinity than the template used in the designing process and AZD9291 (the positive control). None of the designed compounds was found to violate more than the permissible limit set by RO5 thereby predicting their easy transportation, absorption, and diffusion. More so, the designed compounds were found to have good synthetic accessibility which indicates that these designed compounds can be easily synthesized in the laboratory.

Abstract 4053: Mucin 5ac as a potential therapeutic target for KRAS-driven lung adenocarcinoma

Abstract Lung cancer continues to be the leading cause of cancer death in the United States, with more than 140,000 deaths per year. One of the main types of lung cancer is non-small cell lung cancer with lung adenocarcinoma (LUAD) being the most prominent subtype and is mainly due to oncogenic mutations like KRAS, which offers limited and unsuccessful treatments. The mucus barrier produced by mucins, particularly Mucin 5ac (Muc5ac) which is mainly expressed by lung epithelial cells, is essential for airway homeostasis. However, its overproduction can promote respiratory diseases such as chronic obstructive pulmonary disease (COPD), which is known to increase the risk of lung cancer by 3-10 fold. We have previously shown that Muc5ac is commonly expressed in patients with KRAS-driven LUAD and is associated with poor prognosis. Additionally, we found that lack of Muc5ac (genetic deletion) in mice with LUAD either induced chemically by urethane or genetically engineered with mutant KRAS presented with significantly reduced tumor burden. Therefore, we sought a translational approach by inhibiting Muc5ac in our KRAS-driven lung cancer mutant mouse model using an antisense oligonucleotide (ASO) against Muc5ac and hypothesized that the administration of this drug would result in decreased Muc5ac mRNA expression and reduced tumor burden. This was tested by intrapharyngeal administration of either ASO (5mg/kg) or vehicle (saline) twice a week to a cohort of six-week-old KRASG12D mutant mice for a total duration of eight weeks. Our results showed a 5-fold decrease in Muc5ac mRNA expression and a 42% reduction in overall tumor burden when compared to age and sex matched control mice. Additionally, analysis of bronchoalveolar lavage fluid showed a predominance of macrophages with significant downregulation of the protumorigenic M2 type macrophage polarization markers Fizz1 and Arg1 as well as significant upregulation of TNF-a, which suggests a mechanism mediated by direct tumor cytotoxic activity or apoptosis associated with a reduction in macrophage mediated immunosuppressive tumor microenvironment. In conclusion, our study suggests that administration of Muc5ac ASO effectively inhibits mucin production and ameliorates tumor progression, which ultimately could provide insight in both treatments and prevention against KRAS-driven LUAD. Citation Format: Walter V. Velasco Torrez, Shanshan Deng, Marco A. Ramos-Castaneda, Segundo W. Del Aguila-Soto, Seyed Moghaddam. Mucin 5ac as a potential therapeutic target for KRAS-driven lung adenocarcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4053.

Downregulation of ARID1A is correlated with poor prognosis in non-small cell lung cancer.

BackgroundNon-small cell lung cancer (NSCLC) is the main type of lung cancer and NSCLC patients always have a low 5-year survival rate. It is vital to identify a biomarker for the prognosis of NSCLC patients. AT-rich interaction domain 1a (ARID1A) is a tumor suppressor that is involved in the progression of a variety of tumors.MethodsThe ARID1A protein level in NSCLC tissues and paracancerous normal lung (PCNL) tissues were detected with immunohistochemistry (IHC) and western blotting (WB). The χ2 test and Spearman’s rank correlation analysis were carried out to examine the association between ARID1A expression and the clinicopathological features of NSCLC. The Kaplan-Meier method and log-rank test were used to compare overall survival (OS) in the ARID1A low expression group and the ARID1A high expression group.ResultsThe results of WB and IHC demonstrated that the ARID1A protein level was significantly reduced in NSCLC tissues compared with PCNL tissues (P<0.05). The low expression of ARID1A in NSCLC tissues was significantly associated with poor differentiation (P=0.005), smoking (P<0.001), lymphatic invasion (P=0.013), distant metastasis (P=0.010), and high TNM stage (P=0.001). The overall five-year survival rate of NSCLC patients was lower in the ARID1A low expression group than in the ARID1A high expression group. Multivariate analysis showed that the expression of ARID1A had an independent prognostic impact on OS (P=0.024).ConclusionsARID1A may be a novel biomarker for predicting the prognosis of NSCLC patients.

PCN66 IDENTIFICATION OF PATIENTS UNDERGOING TREATMENT OF LUNG CANCER IN THE BRAZILIAN NATIONAL HEALTH SYSTEM (SUS)

Lung cancer was the most common cause of death from cancer in both men and women in the Developed World, and before long, will reach that level in the Developing World as well. The disease has no particular symptoms or signs for its detection at an early stage. It was estimated for Brazil in 2018-2019 the occurrence of 600 thousand new cases of cancer, for each year. Chemotherapy (QT) offers modest survival improvement for patients with non-small cell lung cancer, the modern agents being better tolerated resulting in an improved quality of life. Use real-world data to identify patients and lung cancer types under QT treatment in the SUS. A retrospective patient-centered analysis was performed with data from the Department of Information Technology of Brazilian Public Health System (Datasus) in the 2015, 2016, 2017 and 2018 search by CID-10 and Procedure. The Procedures described for treatment of Lung Cancer in the Data SUS are: QT for Advanced non-small cell lung cancer (QT1), QT for Advanced small cell lung cancer (QT2), prior small cell lung cancer (QT3), Adjuvant Non-Small cell lung cancer (QT4), prior undifferentiated small cell lung cancer (QT5), Adjuvant Small cell lung cancer (QT6). QT1 are involved 60% of the Procedures, (QT1, QT2 and QT3) 34% and (QT4 and QT5) 6% in 2015, QT1 58%, (QT1, QT2 and QT3) 32% and (QT4 and QT5) 10% in 2016, QT1 63%, (QT1, QT2 and QT3) 32% and (QT4 and QT5) 5% in 2017 and QT1 66%, (QT1, QT2 and QT3) 31% and (QT4 and QT5) 3% in 2018. This methodology allows identifying the main types of lung cancer in treatment at the SUS, opening possibility for access strategies based mainly on the new treatments that involves greater survival and quality for the patients.

Dramatically changed immune-related molecules as early diagnostic biomarkers of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the main type of lung cancer, with a low 5-year survival rate because of the absence of effective clinical biomarkers for early diagnosis. Based on the immunosurveillance theory, we proposed that changes in the immune system are more pronounced than tumour-associated antigens during the early stage of cancer. Therefore, a new strategy was designed to screen early diagnostic biomarkers from peripheral leukocytes in early-stage NSCLCs with transcriptome sequencing. A total of 358 immune-related differentially expressed genes were identified between early-NSCLC patients and healthy individuals. Orosomucoid-1 (ORM1, a acute phase protein), the total ORM and chitotriosidase-1 (involved in degradation of chitobiose) were selected for further verification in 210 serum samples by western blotting, ELISA and nephelometry immunoassay (based on immuno-scatter turbidmetry). Receiver operating characteristic curve analysis show that ORM1 and total ORM have excellent diagnostic efficacies, with area under the curve of 0.862 and 0.920, respectively, which significantly distinguished very early-NSCLC (IA) from healthy samples. Flow cytometry results showed that CD15+ neutrophils made up 73% of ORM1+ peripheral leukocytes. In mouse lung cancer model, serum ORM1, but not liver ORM1, changed significantly in the early stage of NSCLC. ORM1 expression in peripheral leukocytes was regulated by TGF-β and mediated by the TGF-β/Smad signalling pathway. Our results indicated that combined ORM and TGF-β could be a promising clinical biomarker in the diagnosis of early NSCLC.

Circular RNA SMARCA5 inhibits the proliferation, migration, and invasion of non-small cell lung cancer by miR-19b-3p/HOXA9 axis.

BackgroundNon-small cell lung cancer (NSCLC) is the main type of lung cancer, remaining a leading cause of cancer-related mortality around the world. Circular RNA SMARCA5 (circSMARCA5) is a novel circular RNA associated with the pathogenesis of several cancers. However, the role of circSMARCA5 in NSCLC remains unknown. In the present study, we aimed to evaluate the functions of circSMARCA5 in NSCLC and the underlying mechanism.MethodsThe expression pattern of circSMARCA5 was determined using qRT-PCR in NSCLC samples and cell lines. The correlation between miR-19b-3p and circSMARCA5 in NSCLC tissues was detected by qRT-PCR. Cell proliferation was examined utilizing CCK-8 assay. Cell migration and invasion was evaluated using Transwell assay. We used the bioinformatics software TargetScan and miRanda to predict circRNA-miRNA and miRNAi-mRNA interactions. Further, the regulatory role of circSMARCA5 in the malignant development of NSCLC in vivo was examined.ResultsThe results showed that circSMARCA5 was down-regulated in NSCLC tissues as compared to the adjacent normal tissues. Overexpression of circSMARCA5 in NSCLC cell lines significantly inhibited the proliferation, migration, and invasion. Furthermore, circSMARCA5 exerted its tumor-suppressive activity through acting as a sponge for microRNA (miR)-19b-3p. Suppression of miR-19b-3p exhibited inhibitory effects on proliferation, migration, and invasion of NSCLC cell lines, which could be attributed to the regulation of homeobox A9 expression. Finally, overexpression of circSMARCA5 inhibited tumor growth in vivo.ConclusionCollectively, circSMARCA5 executed its inhibitory effects on NSCLC cell lines through miR-19b-3p/HOXA9 axis. The results indicated that circSMARCA5 might be a therapeutic target for the treatment of NSCLC.

Weak sharing of genetic association signals in three lung cancer subtypes: evidence at the SNP, gene, regulation, and pathway levels

BackgroundThere are two main types of lung cancer: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC has many subtypes, but the two most common are lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). These subtypes are mainly classified by physiological and pathological characteristics, although there is increasing evidence of genetic and molecular differences as well. Although some work has been done at the somatic level to explore the genetic and biological differences among subtypes, little work has been done that interrogates these differences at the germline level to characterize the unique and shared susceptibility genes for each subtype.MethodsWe used single-nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS) of European samples to interrogate the similarity of the subtypes at the SNP, gene, pathway, and regulatory levels. We expanded these genotyped SNPs to include all SNPs in linkage disequilibrium (LD) using data from the 1000 Genomes Project. We mapped these SNPs to several lung tissue expression quantitative trait loci (eQTL) and enhancer datasets to identify regulatory SNPs and their target genes. We used these genes to perform a biological pathway analysis for each subtype.ResultsWe identified 8295, 8734, and 8361 SNPs with moderate association signals for LUAD, LUSC, and SCLC, respectively. Those SNPs had p < 1 × 10− 3 in the original GWAS or were within LD (r2 > 0.8, Europeans) to the genotyped SNPs. We identified 215, 320, and 172 disease-associated genes for LUAD, LUSC, and SCLC, respectively. Only five genes (CHRNA5, IDH3A, PSMA4, RP11-650 L12.2, and TBC1D2B) overlapped all subtypes. Furthermore, we observed only two pathways from the Kyoto Encyclopedia of Genes and Genomes shared by all subtypes. At the regulatory level, only three eQTL target genes and two enhancer target genes overlapped between all subtypes.ConclusionsOur results suggest that the three lung cancer subtypes do not share much genetic signal at the SNP, gene, pathway, or regulatory level, which differs from the common subtype classification based upon histology. However, three (CHRNA5, IDH3A, and PSMA4) of the five genes shared between the subtypes are well-known lung cancer genes that may act as general lung cancer genes regardless of subtype.

MiR-186 inhibits proliferation, migration, and invasion of non-small cell lung cancer cells by downregulating Yin Yang 1.

Non-small cell lung cancer (NSCLC) is the main type of lung cancer. While miR-186 is significantly reduced in lung cancer tissues and cells, its role in NSCLC has not been completely elucidated. We used qRT-PCR and western blot methods to investigate the levels of miR-186 and YY1 in 21 pairs of NSCLC tissues. Dual luciferase reporter gene assays were performed to detect whether miR-186 directly targets YY1. Next, the roles of miR-186 and its target gene (YY1) in determining the proliferation, apoptosis and migration capabilities of selected cell lines (A549 and HCC827) were investigated by using miR-186 mimics or YY1 siRNA. Our results showed that miR-186 was downregulated and YYI was upregulated in NSCLC tissue, and miR-186 expression was negatively associated with YY1. Similarly, miR-186 was also downregulated and YY1 expression also was upregulated in both A549 and HCC827 cells; furthermore, miR-186 was found to directly target YY1. Cell proliferation, invasion, and migration, as well as apoptosis induction were more strongly inhibited by YY1 siRNA than by miR-186. Our results suggest that miR-186 and its target gene (YY1) could possibly serve as new prognostic biomarkers and therapeutic targets for treating NSCLC in humans.

P2.01-016 Analysis of 5 Differential miRNA Expression in NSCLC Patients

There are two main types of lung cancer: non-small cell lung cancer (NSCLC) which represents 80-85% cases of lung cancer and small cell lung cancer (SCLC) which is about 10-15% cases of lung cancer. The 5-year survival rate for patients with lung cancer vary depending on the stage of the cancer when it is diagnosed. Unfortunately, most of patients with lung cancer are diagnosed on later stage of disease (stage III and IV). In our research we try to find marker among miRNA that can predict occurring of lung cancer on the earlier stage. Isolation of miRNA from plasma was performed by miRCURY RNA Isolation Kit – Biofluids (Exiqon) from NSCLC patients and controls. Synthesis of cDNA and qPCR were carried out using miRCURY LNATM Universal RT microRNA PCR with LNATM enhanced PCR Primers (Exiqon). Statistical calculations were executed on 11 samples as a Pre-eliminary data. Results are shown in the following table. We assed level of 5 different miRNAs circulating in the blood of NSCLC patients using qPCR. Our initial results show that different miRNA can be used to stratify patients and miRNA. Expression of hsa-miR-451a is decreasing in NSCLC versus negative control. Interestingly up-regulated hsa-miR-660-5p was recently described as a prognostic marker in breast cancer but our result preliminary results showed constant decrease in hsa-miR-660-5p expression in all patients’ groups vs controls. The examination on the bigger cohort of patients is necessary to receive a more statistically significant and conclusive data.

EMT influences the expression of CK19 in pleural effusion-derived lung cancer cells and their invasion and metastasis

Lung cancer is the most common cancer after breast and colon cancer, with high rates of mortality, worldwide. There are two main types of lung cancer, small cell lung carcinoma (SCLC), which accounts for approximately 20% of all lung cancer cases and non-SCLC, which accounts for almost 80% of lung cancer cases. Although lung cancer is one of the most aggressive types of cancer, progress in achieving better clinical outcomes has been gradual. Even though a number of markers have been suggested for the diagnosis of lung cancer and monitoring of disease progression, there is no clear way of assessing the invasion, epithelial-mesenchymal transition (EMT) and metastasizing capability of the primary tumor cells. We investigated the incidence of cytokeratin 19 (CK19)-negative expressers in different types of lung cancer from 111 lung cancer patients, their serum and pleural effusion CYFRA21-1 levels and whether induction of EMT in the primary focus cells influences the expression of CK19. In addition, we examined whether CK19-negative lung cancers were more invasive and metastatic. We also examined the propensity of primary focus cells to undergo EMT in the presence of transforming growth factor-β1 (TGF-β1). The results obtained suggested that the invasion and metastasis of lung tumor cells can be assessed by having a complete picture of serum CYFRA21-1 together with the CK19 expression status of primary focus cells and pleural effusion. This assessment may be further improved by examining the propensity of the isolated primary focus cells to undergo TGF-β1 induced EMT in cell culture.

Lung Cancer: Risk Factors, Management, And Prognosis

Lung cancer or lung tumor the most common cause of cancer death in men and second most common in women after breast cancer. Highest rates in North America, Europe, and East Asia, with one third of new cases in China, lower rates in Africa and South Asia. Worldwide in 2012 lung cancer resulted in 1.6 million deaths. Risk factors include smoking, exposure to radon gas, asbestos, second-hand smoke, air pollution, and geneticfactors. Pathogenesis is similar to other cancers, by activation of oncogenes or inactivation of tumor suppressor genes. Two main types of lung cancer are small-cell lung carcinoma(SCLC),and non-small-cell lung carcinoma(NSCLC) Clinical manifestation include coughing, coughing blood, weight loss, weakness, fever or clubbing of the fingernails, hypercalcemia, myasthenia syndrome (muscle weakness), and metastases. Metastatic disease includes weight loss, bone pain and neurological symptoms. Diagnosis mainly by chest radiographs and computed tomography (CT) scans. Lung cancers are classified according to histological type, staging uses TNM (tumor, lymph node and metastases) system. Management depends on cancer specific type, by surgery, radiotherapy and chemotherapy. In the U.S 16.8% survive for at least five years, in England overall five year survival less than 10%.Prevention, cessation of smoking, screening for lung cancer for those long smoking history and between 55 and 80 years. Long term intake of vitamin A,vitamin vitamin D, or vitamin E does not reduce risk of lung cancer. Higher intake of vegetables and fruit tend to lower risk. There is no clear association between diet and lung cancer.

Identification of GlcNAcylated alpha-1-antichymotrypsin as an early biomarker in human non-small-cell lung cancer by quantitative proteomic analysis with two lectins

Background:Non-small-cell lung cancer (NSCLC) is the main type of lung cancer with high mortality rates in worldwide. There is a need to identify better biomarkers to detect NSCLC at an early stage as this will improve therapeutic effect and patient survival rates.Methods:Two lectins (AAL/AAGL and AAL2/AANL), which specifically bind to tumour-related glycan antigens, were first used to enrich serum glycoproteins from the serum of early NSCLC patients, benign lung diseases subjects and healthy individuals. The samples were investigated by using iTRAQ labelling and LC-MS/MS.Results:A total of 53 differentially expressed proteins were identified by quantitative proteomics and four glycoproteins (AACT, AGP1, CFB and HPX) were selected for further verification by western blotting. Receiver operating characteristic analysis showed AACT was the best candidate for early NSCLC diagnosis of the four proteins, with 94.1% sensitivity in distinguishing early tumour Stage (IA+IB) from tumour-free samples (healthy and benign samples, HB). The GlcNAcylated AACT was further detected by lectin-based ELISA and has better advantage in clinical application than total AACT. The GlcNAcylated AACT can effectively differentiate Stage I from HB samples with an AUC of 0.908 and 90.9% sensitivity at a specificity of 86.2%. A combination of GlcNAcylated AACT and carcinoembryonic antigen (CEA) was able to effectively differing Stage I from HB samples (AUC=0.914), which significantly improve the specificity of CEA. The combination application also has the better clinical diagnostic efficacy in distinguishing cancer (NSCLC) from HB samples than CEA or GlcNAcylated AACT used alone, and yielded an AUC of 0.817 with 93.1% specificity.Conclusions:Our findings suggest that the GlcNAcylated AACT will be a promising clinical biomarker in diagnosis of early NSCLC.

Identification of Lung-Cancer-Related Genes with the Shortest Path Approach in a Protein-Protein Interaction Network

Lung cancer is one of the leading causes of cancer mortality worldwide. The main types of lung cancer are small cell lung cancer (SCLC) and nonsmall cell lung cancer (NSCLC). In this work, a computational method was proposed for identifying lung-cancer-related genes with a shortest path approach in a protein-protein interaction (PPI) network. Based on the PPI data from STRING, a weighted PPI network was constructed. 54 NSCLC- and 84 SCLC-related genes were retrieved from associated KEGG pathways. Then the shortest paths between each pair of these 54 NSCLC genes and 84 SCLC genes were obtained with Dijkstra's algorithm. Finally, all the genes on the shortest paths were extracted, and 25 and 38 shortest genes with a permutation P value less than 0.05 for NSCLC and SCLC were selected for further analysis. Some of the shortest path genes have been reported to be related to lung cancer. Intriguingly, the candidate genes we identified from the PPI network contained more cancer genes than those identified from the gene expression profiles. Furthermore, these genes possessed more functional similarity with the known cancer genes than those identified from the gene expression profiles. This study proved the efficiency of the proposed method and showed promising results.

Classification of the Four Main Types of Lung Cancer Using a MicroRNA-Based Diagnostic Assay

For patients with primary lung cancer, accurate determination of the tumor type significantly influences treatment decisions. However, techniques and methods for lung cancer typing lack standardization. In particular, owing to limited tumor sample amounts and the poor quality of some samples, the classification of primary lung cancers using small preoperative biopsy specimens presents a diagnostic challenge using current tools. We previously described a microRNA-based assay (miRview squamous; Rosetta Genomics Ltd., Rehovot, Israel) that accurately differentiates between squamous and nonsquamous non-small cell lung cancer. Herein, we describe the development and validation of an assay that differentiates between the four main types of lung cancer: squamous cell carcinoma, nonsquamous non-small cell lung cancer, carcinoid, and small cell carcinoma. The assay, miRview lung (Rosetta Genomics Ltd.), is based on the expression levels of eight microRNAs, measured using a sensitive quantitative RT-PCR platform. It was validated on an independent set of 451 samples, more than half of which were preoperative cytologic samples (fine-needle aspiration and bronchial brushing and washing). The assay returned a result for more than 90% of the samples with overall accuracy of 94% (95% CI, 91% to 96%), with similar performance observed in pathologic and cytologic samples. Thus, miRview lung is a simple and reliable diagnostic assay that offers an accurate and standardized classification tool for primary lung cancer using pathologic and cytologic samples.

New microRNA-based diagnostic test for lung cancer classification.

10528 Background: Lung cancer is the leading cause of cancer deaths in the US. Treatment options are determined by tumor subtyping, for which there is lack of standardized, objective, and highly accurate techniques. In 20%-30% of cases significant limitations of tumor quantity and quality prevent full classification of the tumor using traditional diagnostic methods. Using microRNA microarray data generated from over a hundred formalin-fixed, paraffin-embedded (FFPE) primary lung cancer samples, we have identified microRNA expression profiles that differ significantly for the main lung cancer types. Based on these findings, we have developed and validated a microRNA-based qRT-PCR assay that differentiates primary lung cancers into four types: squamous cell carcinoma, non-squamous non-small cell lung cancer, carcinoid and small cell carcinoma. Methods: Over 700 primary tumor samples from different histological types of lung cancer were collected. Samples included FFPE blocks from resection or biopsies and cell blocks from cytology specimens including fine needle aspiration, bronchial brushing and bronchial washing. High-quality RNA was extracted from the samples using proprietary protocols. Expression levels of potential microRNA biomarkers were profiled using microarrays followed by a sensitive and specific qRT-PCR platform. An assay for lung tumors classification using 8 microRNAs on qRT-PCR was developed based on data from 261 samples. This assay was validated on an independent blinded set of 451 cytological and pathological samples. Results: Using the expression levels of 8 microRNAs measured in qRT-PCR, accurate classification of the primary lung tumors into the four main cancer types is obtained. The microRNA-based assay reached an accuracy of 94%. Moreover, cytological samples composed over 50% of the validation set and reached an accuracy of 95%. Conclusions: We present here a new microRNA-based assay for the classification of the four main types of lung cancer based only on the expression of 8 microRNAs. This assay displays very high levels of accuracy for both pathological and cytological samples. The assay comprises a standardized, well-tested and objective tool which can assist physicians in the diagnosis of lung cancer.

P4-08-03: Serum Autoantibodies to Breast Cancer Associated Antigens Reflect Tumor Biology: An Opportunity for Early Detection &amp; Prevention?

Abstract Autoantibodies (AABs) are produced as an immune response to abnormal ('non-self') cancer antigens. Previous studies have reported that AABs can be measured in the blood long before cancers are presently diagnosed, e.g., up to 4 years before screening mammography identified breast cancers and up to 5 years before screening CT detected lung cancers. EarlyCDT™-Lung is currently available as an aid to early detection of lung cancer in high risk patients and measures a panel of seven AABs to general cancer antigens and also lung cancer (LC) specific antigens. These AABs have previously been reported to be associated with the two main types of LC i.e., non-small cell and small cell LC. This study looked at AABs to 4 general cancer antigens to evaluate whether their levels reflected different biology in primary breast tumors. Methods 770 patients presented with primary breast cancer to three centers (Nottingham, UK n=323; Munich, Germany n=320; Oklahoma, USA n=127); the median ages and ranges were 61 (26-82), 61 (20-88) &amp; 65 (54-84) years, respectively. All had serum samples taken post-diagnosis and pre-treatment. The tumors were well characterized for histological grade, estrogen receptor (ER), progesterone receptor (PgR) and HER2 status. Serum samples were tested for AABs to four generic cancer antigens(Ags) (p53, SOX2, NY-ESO-1 and Annexin1) originally included as part of Oncimmune's EarlyCDT™-Lung assay. The AABs were measured by ELISA on the Oncimmune platform, and the EarlyCDT™-Lung cutoffs were used to determine positivity. Results 131/770 (17%) of primary breast cancers showed elevated AAB levels to one or more of the limited panel of four generic antigens. Positivity for each AAB was correlated with histological grade, ER, PgR and HER2 status. The results, which were similar for each of the three centres, were combined, and the results are shown in Table 1 below. p53 AAB positive cancers tended to be hormone receptor negative and HER2 positive. NY-ESO-1 positive tumors were almost all higher grade with the majority hormone receptor and HER2 negative. SOX2 positive cancers tended to have a hormone sensitive phenotype (i.e., hormone receptor positive and HER2 negative). Annexin 1 positive cancers also tended to have a hormone sensitive phenotype as well as HER2 negative. The pattern was statistically different for the four AABs (p&amp;lt;0.001). The autoantibody profile for ER positive tumours was not statistically different from PgR positive tumors. Conclusions These data show that specific AABs measured in the serum reflected the biology of the breast cancers. Confirmation of this finding could, in the future, lead to using immuno-biomarkers such as these to guide early therapeutic intervention (e.g. prevention) in a targeted group of women. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-08-03.

Seasonal and geographical variations in lung cancer prognosis in Norway: Does Vitamin D from the sun play a role?

Seasonal and geographical variations in lung cancer prognosis in Norway: Does Vitamin D from the sun play a role?

Lung cancer in asbestos cement workers in Denmark.

To study the relative and absolute risks of main types of lung cancer in a cohort of asbestos cement workers from Denmark. A cohort of 7887 men and 576 women employed between 1928 and 1984 was compiled from the personnel files of Danish Eternit Production. The cohort was followed up for deaths, emigrations, and incident cancer cases during the period 1943-90. The observed number of lung cancer cases in the cohort was compared with the expected number based on incidences for the Danish population. Internal comparison was made with Poisson modelling. A total of 226 lung cancer cases were observed (223 men and three women). The standardised incidence ratio (SIR) for all lung cancer among men was 1.7 (observed number 223, expected number 129.7, 95% confidence interval (95% CI) 1.5-2.0). The SIRs were raised for all main types of lung cancer; adenocarcinoma 2.6, squamous cell carcinoma 1.7, and anaplastic carcinoma 1.5. The higher SIR for adenocarcinomas was found particularly with a latency period of 25 years or more. Among the 93 excess lung cancer cases, 36 were squamous cell carcinomas and 32 were adenocarcinomas. Asbestos cement work is associated with an increased risk of lung cancer of all main types. During the first 25 years after the start of employment this excess risk is shared almost equally between the different histological types of lung cancer, but the risk of adenocarcinomas is clearly higher after this point.