Next-generation molecular therapy in lung cancer

Qian, Jun; Massion, Pierre P.

doi:10.21037/tlcr.2018.01.03

Cited by 7 publications

(6 citation statements)

References 22 publications

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“…The understanding of the pathogenesis of early-stage LUAD has increased with the advent of high-throughput transcriptome sequencing technology; however, the knowledge of the etiology and natural progression of pGGO is limited, especially for pGGO <1 cm in diameter ( 44 ). In this study, we identified DEGs between pGGO <1 cm in diameter and the adjacent normal tissue.…”

Section: Discussionmentioning

confidence: 99%

A Machine-Learning Approach to Developing a Predictive Signature Based on Transcriptome Profiling of Ground-Glass Opacities for Accurate Classification and Exploring the Immune Microenvironment of Early-Stage LUAD

et al. 2022

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Screening for early-stage lung cancer with low-dose computed tomography is recommended for high-risk populations; consequently, the incidence of pure ground-glass opacity (pGGO) is increasing. Ground-glass opacity (GGO) is considered the appearance of early lung cancer, and there remains an unmet clinical need to understand the pathology of small GGO (<1 cm in diameter). The objective of this study was to use the transcriptome profiling of pGGO specimens <1 cm in diameter to construct a pGGO-related gene risk signature to predict the prognosis of early-stage lung adenocarcinoma (LUAD) and explore the immune microenvironment of GGO. pGGO-related differentially expressed genes (DEGs) were screened to identify prognostic marker genes with two machine learning algorithms. A 15-gene risk signature was constructed from the DEGs that were shared between the algorithms. Risk scores were calculated using the regression coefficients for the pGGO-related DEGs. Patients with Stage I/II LUAD or Stage IA LUAD and high-risk scores had a worse prognosis than patients with low-risk scores. The prognosis of high-risk patients with Stage IA LUAD was almost identical to that of patients with Stage II LUAD, suggesting that treatment strategies for patients with Stage II LUAD may be beneficial in high-risk patients with Stage IA LUAD. pGGO-related DEGs were mainly enriched in immune-related pathways. Patients with high-risk scores and high tumor mutation burden had a worse prognosis and may benefit from immunotherapy. A nomogram was constructed to facilitate the clinical application of the 15-gene risk signature. Receiver operating characteristic curves and decision curve analysis validated the predictive ability of the nomogram in patients with Stage I LUAD in the TCGA-LUAD cohort and GEO datasets.

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Section: Discussionmentioning

confidence: 99%

A Machine-Learning Approach to Developing a Predictive Signature Based on Transcriptome Profiling of Ground-Glass Opacities for Accurate Classification and Exploring the Immune Microenvironment of Early-Stage LUAD

et al. 2022

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“…5-years overall survival rate of NSCLS is only about 27% and most NSCLC is diagnosed at the advanced stage, which also contributes to the poor survival rate ( Luo et al, 2019 ). To extend the overall survival of NSCLC patients, many advanced diagnosis and treatment methods have been introduced in clinical interventions, including targeted molecular therapy ( Qian and Massion, 2018 ; Wu et al, 2020a ) and immunotherapy ( Corrales et al, 2018 ; Hao et al, 2020 ). To precisely provide therapeutic interventions, precise molecular classification and diagnosis can significantly improve the overall survival of NSCLC patients, for example osimertinib for EGFR T790M patient therapy ( Mok et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the Different Subtypes of Immune Cell Infiltration to Aid Immunotherapy

Mao

Ding

et al. 2022

Front. Cell Dev. Biol.

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Background?PD-1 ablation or PD-L1 specific monoclonal antibody against PD-1 can recruit the accumulation of functional T cells, leading to tumor rejection in the microenvironment and significantly improving the prognosis of various cancers. Despite these unprecedented clinical successes, intervention remission rates remain low after treatment, rarely exceeding 40%. The observation of PD-1/L1 blocking in patients is undoubtedly multifactorial, but the infiltrating degree of CD8+T cell may be an important factor for immunotherapeutic resistance.Methods:We proposed two computational algorithms to reveal the immune cell infiltration (ICI) landscape of 1646 lung adenocarcinoma patients. Three immune cell infiltration patterns were defined and the relative ICI scoring depended on principal-component analysis.Results:A high ICI score was associated with the increased tumor mutation burden and cell proliferation-related signaling pathways. Different cellular signaling pathways were observed in low ICI score subtypes, indicating active cell proliferation, and may be associated with poor prognosis.Conclusion:Our research identified that the ICI scores worked as an effective immunotherapy index, which may provide promising therapeutic strategies on immune therapeutics for lung adenocarcinoma.

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“…NSCLC is frequently not clinically divided for treatment; however, different histologic subtypes have been shown to respond differently to treatment (7). While some targeted therapies have been developed for patients with lung adenocarcinoma, namely those with activating mutations in EGFR or EML-ALK rearrangements, no targeted therapies are available for patients with any of the other aforementioned subtypes of lung cancer (3,8,9). This is largely due to the differing mutations reported within each histologic subtype.…”

Section: Introductionmentioning

confidence: 99%

miR-31 Displays Subtype Specificity in Lung Cancer

et al. 2021

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miRNA rarely possess pan-oncogenic or tumor-suppressive properties. Most miRNAs function under tissue-specific contexts, acting as either tumor suppressors in one tissue, promoting oncogenesis in another, or having no apparent role in the regulation of processes associated with the hallmarks of cancer. What has been less clear is the role of miRNAs within cell types of the same tissue and the ability within each cell type to contribute to oncogenesis. In this study, we characterize the role of one such tissue-specific miRNA, miR-31, recently identified as the most oncogenic miRNA in lung adenocarcinoma, across the histologic spectrum of human lung cancer. Compared with normal lung tissue, miR-31 was overexpressed in patient lung adenocarcinoma, squamous cell carcinoma, and large-cell neuroendocrine carcinoma, but not small-cell carcinoma or carcinoids. miR-31 promoted tumor growth in mice of xenografted human adenocarcinoma and squamous cell carcinoma cell lines, but not in large- or small-cell carcinoma lines. While miR-31 did not promote primary tumor growth of large- and small-cell carcinoma, it did promote spontaneous metastasis. Mechanistically, miR-31 altered distinct cellular signaling programs within each histologic subtype, resulting in distinct phenotypic differences. This is the first report distinguishing diverse functional roles for this miRNA across the spectrum of lung cancers and suggests that miR-31 has broad clinical value in human lung malignancy. Significance: These findings demonstrate the oncogenic properties of miR-31 in specific subtypes of lung cancer and highlight it as a potential therapeutic target in these subtypes.

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Next-generation molecular therapy in lung cancer

Cited by 7 publications

References 22 publications

A Machine-Learning Approach to Developing a Predictive Signature Based on Transcriptome Profiling of Ground-Glass Opacities for Accurate Classification and Exploring the Immune Microenvironment of Early-Stage LUAD

A Machine-Learning Approach to Developing a Predictive Signature Based on Transcriptome Profiling of Ground-Glass Opacities for Accurate Classification and Exploring the Immune Microenvironment of Early-Stage LUAD

Characterization of the Different Subtypes of Immune Cell Infiltration to Aid Immunotherapy

miR-31 Displays Subtype Specificity in Lung Cancer

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