Transcription profiling of human early stage non-small cell lung carcinoma to refine prognosis for adjuvant therapy
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Potti A
PROVIDER: S-ECPF-GEOD-3593 | biostudies-other | 2006 Aug
REPOSITORIES: biostudies-other
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Project description:Abstract from paper - Potti A, et al Experiment Overall Design: Retrospective analysis of approximately 200 samples obtained from Duke, ACOSOG and CALGB to develop a Lung metagene predictor that would then be used to assess risk of recurrence and thus identify high risk patients with stage Ia non-small cell carcinoma who would be candidates for adjuvant chemotherapy
2008-06-12 | E-GEOD-3593 | biostudies-arrayexpress
Project description:Abstract from paper - Potti A, et al Keywords: Outcome, recurrence, adjuvant therapy, Early stage Non-small cell Lung Cancer, Lung Metgene Predictor
2006-08-10 | GSE3593 | GEO
Project description:Surgery or concurrent chemoradiation are standard of care treatments for patients with localized and locally advanced non-small cell lung cancer (NSCLC). While resection and chemoradiation are potentially curative therapies for early-stage disease, relapse rates remain high. Adjuvant or neoadjuvant chemotherapy improves cure rates 5-15% compared with surgery alone for patients with resectable disease. Immune checkpoint inhibitors (ICI) have heralded a new era for the treatment of advanced NSCLC with one-third of patients experiencing long-term survival. There is increasing interest in examining the role of ICI therapy in patients with early-stage NSCLC. Consolidation durvalumab after chemoradiation has become a part of standard of care for patients with inoperable, locally advanced disease. More recently, there is emerging evidence that neoadjuvant treatment with ICIs results in substantial rates of major pathologic response and pathologic complete response, and high rates of R0 resection with no significant delay in time to surgery. Furthermore, preliminary data show that adjuvant treatment with ICIs after adjuvant chemotherapy improves disease-free survival and may play a critical role in reducing disease recurrence in patients with resectable disease. In this review, we discuss recently reported and ongoing studies that are designed to define the role of immunotherapy in patients with non-metastatic NSCLC.
| S-EPMC8253922 | biostudies-literature
Project description:Surgery is regarded as the primary treatment modality for early stage non-small cell lung cancer (NSCLC), but even after complete resection, a substantial percentage of these patients eventually develop local recurrence or distant metastases. Therefore more effective treatment strategies to reduce lung cancer mortality and recurrence rate are needed. Only recently has the use of adjuvant chemotherapy become standard in early stage NSCLC, at least for stage II and resected IIIA NSCLC. Controversies remain about the benefit for stage I patients. Five-year survival improvements of 5% to 10% have been reported with cisplatin-based adjuvant chemotherapy from multiple large randomized phase III clinical trials and meta-analyses. Questions remain as to which patients benefit and which regimens are best. In this paper, important clinical research in the field of adjuvant chemotherapy of NSCLC is reviewed.
| S-EPMC4367729 | biostudies-literature
Project description:BackgroundEarly-stage non-small cell lung carcinoma (NSCLC) accounts for more than 80% of lung cancer, which is a kind of cancer with high heterogeneity, so the genetic heterogeneity and molecular subtype should be explored.MethodsPartitioning Around Medoid algorithm was used to acquire the molecular subtype for early-stage NSCLC based on prognosis-related mRNAs and methylation sites. Random forest (RF) and support vector machine (SVM) were used to build prediction models for subtypes.ResultsSix prognosis-related subtypes for early-stage NSCLC, including 4 subtypes for lung squamous cell carcinoma (LUSC) and 2 subtypes for lung adenocarcinoma (LUAD), were identified. There were highly expressed and hypermethylated gene regions for LUSC-C1 and LUAD-C2, highly expressed region for LUAD-C1, and hypermethylated regions for LUSC-C3 and LUSC-C4. Molecular subtypes for LUSC were mainly determined by DNA methylation (14 mRNAs and 362 methylation sites). Molecular subtypes for LUAD were determined by both mRNA and DNA methylation information (143 mRNAs and 458 methylation sites). Ten methylation sites were selected as biomarkers for prediction of LUSC-C1 and LUSC-C3, respectively. Nine genes and 1 methylation site were selected as biomarkers for LUAD subtype prediction. These subtypes can be predicted by the selected biomarkers with RF and SVM models.ConclusionsIn conclusion, we proposed a prognosis-related molecular subtype for early-stage NSCLC, which can provide important information for personalized therapy of patients.
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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.
| S-ECPF-GEOD-7898 | biostudies-other
Project description:Lung cancer is worldwide the most common malignancy. Standard of care treatments for early-stage non-small-cell lung cancer (NSCLC) include surgery and adjuvant chemotherapy. However, these patients continue to have poor prognosis due to systemic or local relapse. Immunotherapy has been considered as a novel approach to improve survival in patients with early-stage NSCLC. Since immune checkpoint inhibitors have transformed the treatment of advanced NSCLC, there is a growing interest in the role of immunotherapy in early-stage NSCLC. In this review, we summarize reported and ongoing clinical trials of immunotherapy in both neoadjuvant and adjuvant settings. We also highlight unaddressed issues in this field of research, such as the predictive markers, the optimal combination therapy, and the need for adjuvant immunotherapy. More studies are needed to optimize the treatment regimen of immunotherapy in patients with early-stage NSCLC.
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Project description:Lung cancer is the most common malignant tumor with the highest mortality, and about 84% are non-small cell lung cancer (NSCLC). However, only a small proportion of patients with newly diagnosed lung tumors can receive curative surgery and have a high risk of postoperative recurrence. At present, there are many perioperative treatment methods being continuously explored, such as chemotherapy and targeted therapy, continuously enriching the content of neoadjuvant and adjuvant therapy in early-stage NSCLC. But disappointingly, for patients with driver gene mutation, the significant disease-free survival (DFS) benefit of targeted drugs failed to translate into overall survival (OS) benefit, and for negative patients, chemotherapy has reached a plateau in improving efficacy and survival. Immunotherapy represented by immune checkpoint inhibitors (ICIs) has been researched in more and more clinical trials in patients with early-stage operable disease, gradually enriching the existing treatments. This review focuses on the research progress of clinical trials of neoadjuvant and adjuvant therapy with ICIs in early-stage NSCLC, the exploration of response evaluation and predictive biomarkers, and the urgent problems to be solved in the future.
| S-EPMC7581706 | biostudies-literature
Project description:With the increasingly early stage lung squamous cell carcinoma (LUSC) being discovered, there is an urgent need for a comprehensive analysis of the prognostic characteristics of early stage LUSC. Here, we developed an immune-related gene signature for outcome prediction of early stage LUSC based on three independent cohorts. Differentially expressed genes (DEGs) were identified using CIBERSORT and ESTMATE algorithm. Then, a 17-immune-related gene (RPRM, APOH, SSX1, MSGN1, HPR, ISM2, FGA, LBP, HAS1, CSF2, RETN, CCL2, CCL21, MMP19, PTGIS, F13A1, C1QTNF1) signature was identified using univariate Cox regression, LASSO regression and stepwise multivariable Cox analysis based on the verified DEGs from 401 cases in The Cancer Genome Atlas (TCGA) database. Subsequently, a cohort of GSE74777 containing 107 cases downloaded from Gene Expression Omnibus (GEO) database and an independent data set consisting of 36 frozen tissues collected from National Cancer Center were used to validate the predictive value of the signature. Seventeen immune-related genes were identified from TCGA cohort, which were further used to establish a classification system to construct cases into high- and low-risk groups in terms of overall survival. This classifier was still an independent prognostic factor in multivariate analysis. In addition, another two independent cohorts and different clinical subgroups validated the significant predictive value of the signature. Further mechanism research found early stage LUSC patients with high risk had special immune cell infiltration characteristics and gene mutation profiles. In conclusion, we characterized the tumor microenvironment and established a highly predictive model for evaluating the prognosis of early stage LUSC, which may provide a lead for effective immunotherapeutic options tailored for each subtype.
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Project description:Small-cell lung cancer (SCLC) is one of the most aggressive cancers, yet the molecular mechanisms underlying its devastating clinical outcome remain elusive. In this study, we investigated whether microRNA (miRNA) expression profiles can predict the clinical outcomes of SCLC patients. A total of 82 patients with limited SCLC, who were treated with surgical resection and adjuvant chemotherapy, were enrolled in this study. First, we surveyed the expression of 924 miRNAs from 42 SCLC patients to discover survival-relevant miRNAs and develop prognostic models, which were then validated in an independent cohort of 40 cases using quantitative real-time PCR. We found that the miR-150/miR-886-3p signature was significantly correlated with the overall survival (OS) of SCLC patients (p?=?0.02) in the training set, and both miRNA expression levels were much lower in the SCLC samples than normal lung samples. The miRNA signature also proved to be a significant predictor of survival in the validation set. Patients with high-risk miRNA signatures had poor overall survival (p?=?0.005) and progression-free survival (p?=?0.017) compared with those with low-risk scores. These findings retained statistical significance after adjusting for age, gender and smoking status (HR: 0.26, 95%: CI 0.10-0.69, p?=?0.007), which suggested it may be an independent predictor of survival. In summary, we developed a prognostic miR-150/miR-886-3p signature and validated expression in an independent dataset of resectable SCLC. These preliminary results indicated that miRNAs may serve as promising molecular prognostic markers and new therapeutic targets for SCLC.
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