Clinical Staging Of Non-small Cell Lung Cancer Research Articles

Enhanced NSCLC subtyping and staging through attention-augmented multi-task deep learning: A novel diagnostic tool

ObjectivesThe objective of this study is to develop a novel multi-task learning approach with attention encoders for classifying histologic subtypes and clinical stages of non-small cell lung cancer (NSCLC), with superior performance compared to currently popular deep-learning models. Material and methodsData were collected from six publicly available datasets in The Cancer Imaging Archive (TCIA). Following the inclusion and exclusion criteria, a total of 4548 CT slices from 758 cases were allocated. We evaluated multiple multi-task learning models that integrate attention mechanisms to resolve challenges in NSCLC subtype classification and clinical staging. These models utilized convolution-based modules in their shared layers for feature extraction, while the task layers were dedicated to histological subtype classification and staging. Each branch sequentially processed features through convolution-based and attention-based modules prior to classification. ResultsOur study evaluated 758 NSCLC patients (mean age, 66.2 years ± 10.3; 473 men), spanning ADC and SCC cases. In the classification of histological subtypes and clinical staging of NSCLC, the MobileNet-based multi-task learning model enhanced with attention mechanisms (MN-MTL-A) demonstrated superior performance, achieving Area Under the Curve (AUC) scores of 0.963 (95 % CI: 0.943, 0.981) and 0.966 (95 % CI: 0.945, 0.982) for each task, respectively. The model significantly surpassed its counterparts lacking attention mechanisms and those configured for single-task learning, as evidenced by P-values of 0.01 or less for both tasks, according to DeLong’s test. ConclusionsThe integration of attention encoder blocks into our multi-task learning network significantly enhanced the accuracy of NSCLC histological subtyping and clinical staging. Given the reduced reliance on precise radiologist annotation, our proposed model shows promising potential for clinical application.

Higher accuracy of [68Ga]Ga-DOTA-FAPI-04 PET/CT comparing with 2-[18F]FDG PET/CT in clinical staging of NSCLC.

This study aimed to explore the clinical staging performance of [68Ga]Ga-DOTA-FAPI-04 PET/CT compared with that of 2-[18F]FDG PET/CT in non-small cell lung cancer (NSCLC) patients lesion by lesion. A total of 134 diagnosed or suspected NSCLC patients were enrolled in the prospective study (ChiCTR2000038080); they received paired 2-[18F]FDG PET/CT and [68Ga]Ga-DOTA-FAPI-04 PET/CT. Of these patients, the retrospective analysis of 74 NSCLC patients with pathological results was conducted from primary tumor (T) diagnosis, lymph node (N), and metastatic lesion (M) staging. The imaging characteristics of the lung nodules and suspected metastases were obtained and analyzed, and the staging performance of 2-[18F]FDG PET/CT and [68Ga]Ga-DOTA-FAPI-04 PET/CT was compared. For T diagnosis, [68Ga]Ga-DOTA-FAPI-04 showed better diagnostic performance than 2-[18F]FDG in 79 lung nodules of 72 patients, especially for nonsolid and small-dimension adenocarcinoma nodules. For N staging, 98 lymph nodes (LNs) with pathological results in 37 patients were analyzed. The SUVmax of [68Ga]Ga-DOTA-FAPI-04 in the nonmetastatic LNs was significantly lower than that in the metastatic LNs. Regarding metastatic LN identification, the calculated optimum cut-off value of [68Ga]Ga-DOTA-FAPI-04 SUVmax was 5.5, and the diagnostic accuracy using [68Ga]Ga-DOTA-FAPI-04 and 2-[18F]FDG criteria was 94% and 30%, respectively (P < 0.001). For M staging, [68Ga]Ga-DOTA-FAPI-04 identified more lesions than 2-[18F]FDG (257 vs. 139 lesions) in 14 patients with multiple metastases. Overall, the staging accuracy of [68Ga]Ga-DOTA-FAPI-04 was better than that of 2-[18F]FDG in 52 patients with different pathological stages [43/52 (82.7%) vs. 27/52 (51.9%), P = 0.001]. Compared with 2-[18F]FDG PET/CT, [68Ga]Ga-DOTA-FAPI-04 PET/CT demonstrated better staging performance in NSCLC patients with different pathological stages, especially those with localized disease.

Correlation between loss of Smad4 and clinical parameters of non-small cell lung cancer: an observational cohort study

BackgroundSMAD4 has been found to be inactivated to varying degrees in many types of cancer; the purpose of this study was to investigate the correlation between SMAD4 expression in non-small cell lung cancer (NSCLC) and clinical pathological parameters.MethodsThe serum concentration of SMAD4 was measured by enzyme-linked immunosorbent assay and its histological expression was quantified by immunohistochemistry.ResultsThe serum concentration of Smad4 in patients with NSCLC was lower than that in benign lung disease patients and healthy individuals (P < 0.001) and its concentration was related to the histological classification, pathological differentiation, lymphatic metastasis and clinical stage of NSCLC. The sensitivity and specificity of serum Smad4 were 91.56% and 61.56% for screening NSCLC from healthy individuals and 84.55% and 60.36% for screening NSCLC from patients with benign lung disease. Logistic regression analysis showed that the degree of cell differentiation (P < 0.001), lymph node metastasis (P < 0.001) and clinical stage of NSCLC (P = 0.007) affected the expression of Smad4, and had a strong correlation with the expression of Smad4. The expression of Smad4 in NSCLC tissues was lower than that in normal lung tissues (P = 0.009) and its expression was related to the degree of tissue differentiation, lymph node metastasis and clinical stage (P < 0.05).ConclusionsThe downregulation or deletion of Smad4 is related to the malignant biological behavior of NSCLC and serum Smad4 could be considered as a potential molecular indicator for diagnosis and evaluation of NSCLC.

Akciğer Kanserli Hastalarda F-18 FDG PET/BT Parametrelerinin Klinik Evre ile İlişkisi

Aim: It was aimed to investigate the relationship of disease clinical stage between the maximum diameter of primer lesion (LEGC), maximum of standardized uptake value (SUVmax), mean of standardized uptake value (SUVmean), tumor volume (TV) and total lesion glycolysis (TLG) values derived from positron emission tomography/computed tomography (PET/CT) images. Method: The information of 130 lung cancer patients diagnosed histopathologically between 01.01.2012 and 31.12.2014 in Necmettin Erbakan University Nuclear Medicine Department of Meram Medical Faculty scanned for PET-CT for lung cancer diagnosis and staging, were included in this study. The values of the maximum diameter of primer lesion, SUVmax, SUVmean, TLG and MTV derived from PET-CT scanning and their histopathological subtypes, other clinical and radyological information of patients were noted. The non-small cell lung cancer patients were graded according to tumor diameter, nodal and involvement metastasis (TNM) staging system using clinical information, PET-CT and other radyological test results if any. On the other hand, the small cell carcinoma diagnosed were categorised as limited or extensive stage. Findings: In this study, the mean age of 118 men and 12 women, totally 130 patients, was evaluated 63,46 ±9,96 ( range 40-87 age ). The patients were classified as 106 non-small cell lung Cancer (NSCLC) (81.5%) ve 24 small cell lung cancer (SCLC) (18.5%). The histopathologically diagnosed NSCLC patients were consists of 62 squamous cell cancers, 39 adeno cancers, and 5 other types (3 carcinoid tumors, 1 large cell cancer and 1 sarcomatoid tumor). Results: In our study, it was observed that there was no significant relationship between the maximum diameter of the lesion, SUVmax, SUVmean, MTV and TLG values among SCLC and NSCLC patients. Additionally, it was also found that there was no correlation between these parameters and the SCLC stage. The maximum diameter of the lesion, SUVmax, SUVmean, MTV and TLG parameters were related with stage. Conclusion: Higher SUVmax, SUVmean, TV, and TLG values of the primary tumor were determined to predict the more advanced clinical stage in NSCLC. This relationship between metabolic parameters and the clinical stage suggest that PET / CT may be valuable in terms of providing prognostic information in NSCLC.

P54.03 Multiple Microarray Analyses Identify Key Genes Associated with the Development of NSCLC from COPD

Chronic obstructive pulmonary disease (COPD) is an independent risk factor of non-small cell lung cancer (NSCLC). This study aimed to analyze the key genes and potential molecular mechanisms that are involved in the development from COPD to NSCLC. Expression profiles of COPD and NSCLC in GSE106899, GSE12472, and GSE12428 were downloaded from the Gene Expression Omnibus (GEO) database, followed by identification of the differentially expressed genes (DEGs) between COPD and NSCLC. Based on the identified DEGs, functional pathway enrichment and lung carcinogenesis-related networks analyses were performed and further visualized with Cytoscape software. Then, principal component analysis (PCA), cluster analysis, and support vector machines (SVM) verified the ability of the top modular genes to distinguish COPD from NSCLC. Additionally, the corrections between these key genes and clinical staging of NSCLC were studied using the UALCAN and HPA websites. Finally, a prognostic risk model was constructed based on multivariate Cox regression analysis. Kaplan-Meier survival curves of the top modular genes on the training and verification sets were generated. A total of 2350, 1914, and 1850 DEGs were obtained from GSE106899, GSE12472, and GSE12428 datasets, respectively. Following analysis of protein-protein interaction networks, the identified modular gene signatures containing H2AFX, MCM2, MCM3, MCM7, POLD1, and RPA1 were identified as markers for discrimination between COPD and NSCLC. The modular gene signatures were mainly enriched in the processes of DNA replication, cell cycle, mismatch repair, and others. Besides, the expression levels of these genes were significantly higher in NSCLC than in COPD, which was further verified by the immunohistochemistry. In addition, the high expression levels of H2AFX, MCM2, MCM7, and POLD1 correlate with poor prognosis of lung adenocarcinoma (LUAD). The Cox regression prognostic risk model showed the similar results and the predictive ability of this model is independent of other clinical variables. This study revealed several key modules that closely relate to NSCLC with underlying disease COPD, which provide a deeper understanding of the potential mechanisms underlying the malignant development from COPD to NSCLC. This study provides valuable prognostic factors in high-risk lung cancer patients with COPD.

Multiple microarray analyses identify key genes associated with the development of Non-Small Cell Lung Cancer from Chronic Obstructive Pulmonary Disease.

Introduction: Chronic obstructive pulmonary disease (COPD) is an independent risk factor of non-small cell lung cancer (NSCLC). This study aimed to analyze the key genes and potential molecular mechanisms that are involved in the development from COPD to NSCLC.Methods: Expression profiles of COPD and NSCLC in GSE106899, GSE12472, and GSE12428 were downloaded from the Gene Expression Omnibus (GEO) database, followed by identification of the differentially expressed genes (DEGs) between COPD and NSCLC. Based on the identified DEGs, functional pathway enrichment and lung carcinogenesis-related networks analyses were performed and further visualized with Cytoscape software. Then, principal component analysis (PCA), cluster analysis, and support vector machines (SVM) verified the ability of the top modular genes to distinguish COPD from NSCLC. Additionally, the corrections between these key genes and clinical staging of NSCLC were studied using the UALCAN and HPA websites. Finally, a prognostic risk model was constructed based on multivariate Cox regression analysis. Kaplan-Meier survival curves of the top modular genes on the training and verification sets were generated.Results: A total of 2350, 1914, and 1850 DEGs were obtained from GSE106899, GSE12472, and GSE12428 datasets, respectively. Following analysis of protein-protein interaction networks, the identified modular gene signatures containing H2AFX, MCM2, MCM3, MCM7, POLD1, and RPA1 were identified as markers for discrimination between COPD and NSCLC. The modular gene signatures were mainly enriched in the processes of DNA replication, cell cycle, mismatch repair, and others. Besides, the expression levels of these genes were significantly higher in NSCLC than in COPD, which was further verified by the immunohistochemistry. In addition, the high expression levels of H2AFX, MCM2, MCM7, and POLD1 correlate with poor prognosis of lung adenocarcinoma (LUAD). The Cox regression prognostic risk model showed the similar results and the predictive ability of this model is independent of other clinical variables.Conclusions: This study revealed several key modules that closely relate to NSCLC with underlying disease COPD, which provide a deeper understanding of the potential mechanisms underlying the malignant development from COPD to NSCLC. This study provides valuable prognostic factors in high-risk lung cancer patients with COPD.

Novel PD-L1 mAb HC16 reveals upregulation of PD-L1 in BAC subtype.

Programmed death-ligand 1 (PD-L1) is an inhibitory transmembrane protein that can prevent autoimmune response. Upregulated PD-L1 serves as a predictive biomarker for patients who may respond well to immune checkpoint therapies. However, variable associations of PD-L1 level with prognoses have been reported. In this study, a short peptide sequence corresponding to PD-L1 amino acids 172-187 (from the extracellular Ig-like C-type domain, and with high predicted antigenicity and hydrophilicity) was used to generate a monoclonal antibody (mAb). The resultant PD-L1 mAb, clone HC16, was examined for binding specificity and reactivity in cancer cell-lines, as assessed by immunocytochemical, immunoblotting, and co-immunoprecipitation. The potential diagnostic and clinical applicability of clone HC16 was further tested using malignant tissue arrays derived from various cancer types analyzed with an automated immunohistochemical (IHC) staining platform. Additionally, tumor samples from patients diagnosed with non-small cell lung cancer (NSCLC) were analyzed by western blotting. Clone HC16 showed obvious staining activity in lung and breast cancer tissues. Interestingly, we observed that PD-L1 level was negatively associated with clinical stage in NSCLC. Strong PD-L1 expression tended to be found in patients diagnosed with bronchioloalveolar carcinoma (BAC). These results demonstrate that clone HC16 harbors good target specificity and is suitable for further development in diagnostic tools to assess PD-L1 expression in human tissues. In addition, our findings also suggest a role for PD-L1 in a non-invasive subtype of lung cancer.

TPX2 Promotes Metastasis and Serves as a Marker of Poor Prognosis in Non-Small Cell Lung Cancer

BackgroundMetastasis contributes to the high mortality rate of non-small cell lung cancer (NSCLC), and gaining a better understanding of its metastatic mechanisms would aid in initiating effective clinical treatment.Material/MethodIn this study, bioinformatics analyses of the GEO database and TCGA-LUAD were first used to identify the key node gene regulating NSCLC malignant progression. Further in vitro experiments, including wound healing assay, invasion assay, Western blot assay, and luciferase report assay, were used to clarify the functions and mechanism of TPX2 in NSCLC.ResultsResults of the TCGA analysis showed that TPX2 was significantly positively correlated with tumor metastasis and growth and the clinical stage of NSCLC. In addition, high levels of TPX2 significantly indicated a poor survival rate. In vitro experimental results also revealed that the upregulation of TPX2 significantly promoted NSCLC cell migration and invasion and could affect cell replasticity. Further results indicated that TPX2 significantly activated the epithelial-mesenchymal transition process and promoted the expression and activities of matrix metalloproteinase (MMP)2 and MMP9.ConclusionsThis study demonstrated that TPX2 promotes the metastasis and malignant progression of NSCLC and could thus serve as a marker of poor prognosis in NSCLC.

Aberrantly High Expression Of NOK/STYK1 Is Tightly Associated With The Activation Of The AKT/GSK3β/N-Cadherin Pathway In Non-Small Cell Lung Cancer.

PurposeHigh metastasis is a leading risk factor for the survival of non-small cell lung cancer (NSCLC) and epithelial-mesenchymal transition (EMT) is a vital step of metastasis. The expression of novel oncogene with kinase domain (NOK) has been observed in some human malignancies, including non-small cell lung cancer (NSCLC); however, the biological function of NOK in NSCLC remains unclear. In the study, we explored the function of NOK in NSCLC, with an aim to elucidate the relevant underlying mechanisms.Patients and methodsWe investigate the expression of NOK, p-Akt, p-GSK-3β, E-cadherin and N-cadherin expression by immunohistochemical analysis using tissue microarrays of 72 paired NSCLC samples of cancerous and adjacent normal tissues. The associations between NOK expression and clinicopathological factors, overall survival, other proteins were assessed. Immunofluorescence analysis of NSCLC tissues was performed to study the location of NOK, Akt and GSK-3β. Up or down-regulated of NOK were conducted in two NSCLC cell lines to analyze its impact on AKT/GSK3β pathway.ResultsStatistical analysis revealed NOK expression increased in NSCLC tissues compared with normal tissues (P<0.05). It also showed that low NOK expression were associated with a higher possibility of non-lymphatic metastasis, an early pN stage and clinical stage (P<0.05). Moreover, NOK expression was positively correlated with the expression of oncogene p-Akt (Thr308), p-GSK-3β (Ser9) and N-cadherin (P<0.05). Immunofluorescence analysis of NSCLC tissues revealed that NOK is co-located with Akt and GSK-3β. Further study in NSCLC cell lines revealed that NOK overexpression can activate the AKT/GSK3β pathway. Conversely, knockdown of NOK can suppress the AKT/GSK3β pathway.ConclusionOur results suggest that NOK overexpression correlated significantly with lymphatic metastasis, advanced pN and clinical stage in NSCLC. And NOK may promote EMT by activating the AKT/GSK3β/N-cadherin pathway in NSCLC.

Overexpression of LIMD2 promotes the progression of non-small cell lung cancer.

LIM domain containing 2 (LIMD2) is a small LIM-only protein that has been demonstrated to promote tumor progression; however, the expression and function of LIMD2 in non-small cell lung cancer (NSCLC) has not previously been reported. In the present study, reverse transcription-quantitative PCR and western blot analysis were conducted to examine the mRNA and protein expression levels of LIMD2. Cell Counting Kit-8, Transwell and wound-healing assays were performed in order to examine cell proliferation, invasion and migration, respectively. The data revealed that the LIMD2 expression levels were significantly increased in NSCLC tissues and cell lines, compared with adjacent non-tumor tissues and normal lung epithelial cells, respectively. In addition, the high expression of LIMD2 was significantly associated with lymph node metastasis, distant metastasis and advanced clinical stage in NSCLC. The patients with NSCLC with a high expression of LIMD2 exhibited shorter survival times than those with low LIMD2 expression. The knockdown of LIMD2 caused remarkable decreases in NSCLC cell proliferation, migration and invasion. Bioinformatics analysis and luciferase reporter gene assay data further confirmed that LIMD2 was a direct target gene of microRNA-124 (miR-124), a well-known tumor suppressor in NSCLC. The expression of LIMD2 was negatively regulated by miR-124 in NSCLC cells. In addition, miR-124 was downregulated in NSCLC tissues compared with adjacent non-tumor tissues, and an inverse correlation was observed between the expression of LIMD2 and miR-124 in NSCLC tissues. In conclusion, the present study demonstrates that LIMD2 serves an oncogenic role in NSCLC, suggesting that it may be used as a potential therapeutic target for the treatment of NSCLC.

Invited letter to the editor on the editorial on "Clinical staging of NSCLC: current evidence and implications for adjuvant chemotherapy".

It is with great interest that we took notice of the expert knowledge on staging of non-small cell lung cancer (NSCLC) and the implications on adjuvant chemotherapy expressed in the two invited editorials on our previously published article entitled “ Clinical staging of NSCLC: current evidence and implications for adjuvant chemotherapy ” (1).

Clinical staging of NSCLC: current evidence and implications for adjuvant chemotherapy.

Survival of all non-small cell lung cancer (NSCLC) patients is disappointing, with a 5-year survival of 18%. Staging NSCLC patients is crucial because it determines the choice of treatment and prognosis. Clinical staging is a complex process that comes with many challenges and with low accuracy between the clinical and pathological stage. Treatment modalities for stage I–III NSCLC consist of surgical resection, radiotherapy and chemotherapy. This review describes the current evidence on staging and the implications on adjuvant chemotherapy. For stage I disease, staging is most accurate. Primary treatment consists of surgery or stereotactic ablative radiotherapy. When a patient has stage II disease, staging is less accurate because more diagnostic modalities are necessary to stage the mediastinal lymph nodes. Surgery remains the primary treatment modality and platinum-based adjuvant chemotherapy gives a 4% 5-year survival benefit. Staging patients with stage III disease is difficult because of the heterogeneity of the patients. It should be decided if a patient has potentially resectable disease with or without risk of incomplete resection. Induction therapy with chemo(radio)therapy followed by surgical resection or definitive chemoradiotherapy are the treatments of choice. The 5-year survival can reach 44% in selected patients. Decisions in staging and treating patients with NSCLC should be made by a multidisciplinary team with sufficient expertise in all aspects of staging and treatment.

B-Myb Is Up-Regulated and Promotes Cell Growth and Motility in Non-Small Cell Lung Cancer.

B-Myb is a transcription factor that is overexpressed and plays an oncogenic role in several types of human cancers. However, its potential implication in lung cancer remains elusive. In the present study, we have for the first time investigated the expression profile of B-Myb and its functional impact in lung cancer. Expression analysis by quantificational real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry demonstrated that B-Myb expression is aberrantly overexpressed in non-small cell lung cancer (NSCLC), and positively correlated with pathologic grade and clinical stage of NSCLC. A gain-of-function study revealed that overexpression of B-Myb significantly increases lung cancer cell growth, colony formation, migration, and invasion. Conversely, a loss-of-function study showed that knockdown of B-Myb decreases cell growth, migration, and invasion. B-Myb overexpression also promoted tumor growth in vivo in a NSCLC xenograft nude mouse model. A molecular mechanistic study by RNA-sequencing (RNA-seq) analysis showed that B-Myb overexpression causes up-regulation of various downstream genes (e.g., COL11A1, COL6A1, FN1, MMP2, NID1, FLT4, INSR, and CCNA1) and activation of multiple critical pathways (e.g., extracellular signal-regulated kinases (ERK) and phosphorylated-protein kinase B (Akt) signaling pathways) involved in cell proliferation, tumorigenesis, and metastasis. Collectively, our results indicate a tumor-promoting role for B-Myb in NSCLC and thus imply its potential as a target for the diagnosis and/or treatment of NSCLC.

Correlation of EGFR gene amplification with invasion and metastasis of non-small cell lung cancer.

The aim of this study was to explore epidermal growth factor receptor (EGFR) gene amplification and its relationship with cancer invasion and metastasis in non-small cell lung cancer (NSCLC). EGFR amplification in 45 patients with NSCLC and 15 subjects with normal lung tissues was detected by fluorescence in situ hybridization. The relationship between EGFR amplification and the clinicopathologic features of NSCLC was analyzed. EGFR gene amplifications were identified in 2 of 15 normal lung tissues (13.33%) and in 29 of 45 NSCLCs (64.44%). Patients <60 years had a 66.67% EGFR amplification rate, while patients ≥60 years had a rate of 62.50%. The EGFR amplification rates in male and female patients were 64.0% (16/25) and 65.0% (13/20), respectively. Pathologically, the EGFR amplification rate of patients with squamous cell carcinoma was 56.52% (13/23), and with adenocarcinoma was 72.72% (16/22). The EGFR amplification rate in NSCLCs with well-moderate differentiation was lower than in those with poor differentiation; 48.0% (12/25) vs 85.0% (17/20), respectively. Patients with lymph node metastasis had nearly double the amplification rate than those without metastasis; 90.0% (18/20) vs 44.0% (11/25), respectively. The rate of EGFR amplification was significantly higher in NSCLC than in normal lung tissue (64.44 vs 13.33%, P < 0.05), and was not correlated with age or gender (P > 0.05), but increased with clinical stage in NSCLCs (P < 0.05). Overall, these studies found that the rate of EGFR gene amplification was increased significantly in NSCLC and was closely related to lymphatic metastasis and TNM stage.

Influence of Gastrointestinal Tract Cancer History on the Outcomes of Lung Cancer Surgery: Extended Inclusion Criteria for Clinical Trials

ABSTRACT Aim: Clinical trials often exclude patients with a history of cancer treatment during the 5 years preceding the investigation. This study aims to evaluate whether a history of gastrointestinal (GI) tract cancer affects the prognosis of patients who undergo surgery for non-small cell lung cancer (NSCLC) to extend inclusion criteria for clinical trials. Methods: Multi-institutional, individual data from patients with NSCLC resected between 2000 and 2013 were collected. The patients were divided into 2 groups: those with a history of GI tract cancer (GI group) and those without any history (non-GI group). We compared the outcomes with well-matched groups using propensity scoring to minimize bias related to the nonrandomness. The influence of GI tract cancer stage, disease-free interval (DFI), and treatment method for GI tract cancer on the outcome of NSCLC was examined. Results: We analyzed 196 patients in the GI group and 3732 in the non-GI group. In unmatched cohort, multivariate analyses showed that a history of GI tract cancer did not affect overall survival (OS: hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.68-1.32) or recurrence-free survival (RFS: HR 0.94; 95%CI 0.71-1.25). Independent predictors of poor prognosis included older age, male sex, high carcinoembryonic antigen levels, and advanced clinical stage of NSCLC. The two groups in matched cohort demonstrated equivalent OS (OS: HR 0.90; 95%CI 0.60-1.33) and RFS (RFS: HR 0.84; 95%CI 0.60-1.18), even in patients with clinical stage I. GI tract cancer stage, DFI, and treatment method for GI tract cancer were not associated with outcomes. Conclusions: Patients with well-controlled GI tract cancer treated during the last 5 years can be included in randomized controlled trials for NSCLC.Patients with well-controlled GI tract cancer treated during the last 5 years can be included in randomized controlled trials for NSCLC. Disclosure: All authors have declared no conflicts of interest.

P-137 * HIGH-QUALITY SECRETOME OF A549 CELLS AIDED THE DISCOVERY OF C4B-BINDING PROTEIN AS A NOVEL SERUM BIOMARKER FOR NON-SMALL-CELL LUNG CANCER

Cancer secretomes are a promising source for biomarker discovery. The analysis of cancer secretomes still faces some difficulties mainly related to the intracellular contamination, which hinders the qualification and follow-up validations. This study aimed to establish a high-quality secretome of A549 cells by using the cellular proteome as a reference and to test the merits of this refined secretome for biomarker discovery for non-small cell lung cancer (NSCLC). Using one-dimensional gel electrophoresis followed by liquid-chromatography tandem mass spectrometry, we comprehensively investigated the secretome and the concurrent cellular proteome of A549 cells. A high-quality secretome consisting of 382 proteins was refined from 889 initial secretory proteins. More than 85.3% of proteins were annotated as secreted and 76.8% as extracellular or membrane-bound. The discriminative power of the lung-cancer associated secretome was confirmed by gene expression and serum proteomic data. The elevated level of C4b-binding Protein (C4BP) in NSCLC blood was verified by enzyme-linked immunosorbent assays (ELISA, p = 6.07e-6). Moreover, the serum C4BP level in 89 patients showed a strong association with the clinical staging of NSCLC. Our reference-experiment-driven strategy is simple and widely applicable, and may facilitate the identification of novel promising biomarkers of lung cancer. (C) 2011 Elsevier B.V. All rights reserved.

Variation of Blood T Lymphocyte Subgroups in Patients with Non- small Cell Lung Cancer

To study variation in T lymphocyte subgoups and its clinical significance in non-small cell lung cancer (NSCLC). Levels of CD3+ , CD4+ , CD8+ , CD4+/CD8+, NK and Treg cells in peripheral blood of NSCLC cases and healthy adults were determined by flow cytometry. CD3+ , CD4+ and CD4+/CD8+ ratio and NK cells in NSCLCs were decreased significantly in comparison with the control group (P < 0.01), and decreased with increase in the clinical stage of NSCLC, while CD8+ cells demonstrated no significant change (P > 0.05). Treg cells were significantly more frequent than in the control group (P < 0.01), and increased with the clinical stage of NSCLC. The cellular immune function of the NSCLC patients is lowered. It is important to detect change of T lymphocyte subgroups by flow cytometry for the diagnosis, treatment and prognostic assessment of NSCLC patients.

A high-quality secretome of A549 cells aided the discovery of C4b-binding protein as a novel serum biomarker for non-small cell lung cancer

Cancer secretomes are a promising source for biomarker discovery. The analysis of cancer secretomes still faces some difficulties mainly related to the intracellular contamination, which hinders the qualification and follow-up validations. This study aimed to establish a high-quality secretome of A549 cells by using the cellular proteome as a reference and to test the merits of this refined secretome for biomarker discovery for non-small cell lung cancer (NSCLC). Using one-dimensional gel electrophoresis followed by liquid-chromatography tandem mass spectrometry, we comprehensively investigated the secretome and the concurrent cellular proteome of A549 cells. A high-quality secretome consisting of 382 proteins was refined from 889 initial secretory proteins. More than 85.3% of proteins were annotated as secreted and 76.8% as extracellular or membrane-bound. The discriminative power of the lung-cancer associated secretome was confirmed by gene expression and serum proteomic data. The elevated level of C4b-binding Protein (C4BP) in NSCLC blood was verified by enzyme-linked immunosorbent assays (ELISA, p = 6.07e-6). Moreover, the serum C4BP level in 89 patients showed a strong association with the clinical staging of NSCLC. Our reference-experiment-driven strategy is simple and widely applicable, and may facilitate the identification of novel promising biomarkers of lung cancer.

Relationship between chemosensitivity in vitro and the expression of GRP78 in non-small cell lung cancer

The expressive level of glucose-regulated protein 78 (GRP78) is elevated and correlated with resistance of chemotherapy drugs in breast cancer cell. However, little is known about the relationship between its expression and drug resistance in non-small cell lung cancer (NSCLC). The aim of this study was to explore the relationship between drug resistance and the expression of GRP78 in NSCLC. Drug sensitivity test was used to detect the resistance to 8 chemotherapy drugs in 52 NSCLC fresh surgical samples by methylthiazoletrazolium (MTT), and expression of GRP78 was detected by immunohistochemistry method. Spearman correlation assay was used to investigate the correlation between the GRP78 expression and drug resistance. The resistance rates to paclitaxel (PTX), adriamycin (ADM), carboplatin (CBP), topotecan (TPT), navelbine (NVB), vincristine (VCR), cisplatin (DDP) and etoposide (VP-16) of the 52 samples were 42.31%, 57.69%, 63.46%, 65.38%, 67.31%, 73.08%, 78.85%, 90.38%, respectively. Fourteen cases showed the complete resistance to the total 8 chemotherapy drugs. Furthermore, the expression of GRP78 was stronger in poorly differentiated cancer as compared with the well and moderately differentiated cancer (P < 0.05), so as in stage II and III cancer than in stage I cancer (P < 0.05). Spearman correlation assay showed that there was a correlation between the chemotherapeutics resistance to ADM, VP-16, VCR, TPT and the expression of GRP78 in NSCLC (P < 0.05). It is feasible to detect the drug sensitivity to chemotherapy for tumor cells by MTT method. The results of chemosensitivity assay in vitro are indicative of clinical drug administration in NSCLC. The detection of GRP78 isalso indicative of the resistance to chemotherapy drugs and the differentiation and the clinical stage in NSCLC.