Early-Stage NSCLC: Advances in Thoracic Oncology 2018

Osarogiagbon, Raymond U.; Veronesi, Giulia; Fang, Wentao; Ekman, Simon; Suda, Kenichi; Aerts, Joachim; Donington, Jessica S.

doi:10.1016/j.jtho.2019.02.029

Cited by 44 publications

(38 citation statements)

References 87 publications

(95 reference statements)

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“…Surgical resection offers the most effective treatment for early-stage LUSC [10]. Adjuvant chemotherapy or EGFR-TKI improves the survival of stage II-III lung cancer patients after surgery [11,12].…”

Section: Discussionmentioning

confidence: 99%

Identification of an Immune Gene Expression Signature for Predicting Lung Squamous Cell Carcinoma Prognosis

Yan

Zhang

2020

BioMed Research International

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Growing evidence indicates that immune-related biomarkers play an important role in tumor processes. This study investigates immune-related gene expression and its prognostic value in lung squamous cell carcinoma (LUSC). A cohort of 493 samples of patients with LUSC was collected and analyzed from data generated by the TCGA Research Network and ImmPort database. The R coxph package was employed to mine significant immune-related genes using univariate analysis. Lasso and stepwise regression analyses were used to construct the LUSC prognosis prediction model, and clusterProfiler was used for gene functional annotation and enrichment analysis. The Kaplan-Meier analysis and ROC were used to evaluate the model efficiency in predicting and classifying LUSC case prognoses. We identified 14 immune-related genes to incorporate into our prognosis model. The patients were divided into two subgroups (Risk-H and Risk-L) according to their risk score values. Compared to Risk-L patients, Risk-H patients showed significantly improved overall survival (OS) in both training and testing sets. Functional annotation indicated that the 14 identified genes were mainly enriched in several immune-related pathways. Our results also revealed that a risk score value was correlated with various signaling pathways, such as the JAK-STA signaling pathway. Establishment of a nomogram for clinical application demonstrated that our immune-related model exhibited good predictive prognostic performance. Our predictive prognosis model based on immune signatures has potential clinical implications for assessing the overall survival and precise treatment for patients with LUSC.

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Section: Discussionmentioning

confidence: 99%

Identification of an Immune Gene Expression Signature for Predicting Lung Squamous Cell Carcinoma Prognosis

Yan

Zhang

2020

BioMed Research International

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“…In addition, an anti-PD-L1 antibody drug, durvalumab, has also been approved to treat unresectable Stage III NSCLC after concurrent platinum-based chemotherapy and radiation therapy. Following these successes of immunotherapies in lung cancers, researchers and clinicians are trying these drugs to treat earlier-stage NSCLC in neoadjuvant or adjuvant settings [16]. For example, Forde and colleagues reported, in their pilot study, that two preoperative doses of the PD-1 inhibitor, nivolumab, conferred a major pathological response in 9 of 20 resected tumors (45%) [17].…”

Section: Discussionmentioning

confidence: 99%

Comparison of PD-L1 Expression Status between Pure-Solid Versus Part-Solid Lung Adenocarcinomas

et al. 2019

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Although lung adenocarcinomas (LADs) with ground-glass opacity (GGO; part-solid tumors) have been shown to differ from those without GGO (pure-solid tumors) in clinicopathological features and prognoses, whether programmed death ligand-1 (PD-L1) protein expression differs between these two tumor types is unclear. This study included 124 patients with clinical T1a–c LAD who received pulmonary resections during 2007–2009. The E1L3N antibody was used to stain for PD-L1 in primary LAD specimens. The specimens were considered PD-L1+ if ≥1% of tumor cells showed membrane staining, and were classified as having a high PD-L1+ tumor proportion score (TPS) if ≥50% of the tumor cells did so. Among the 124 patients, 45 had part-solid tumors and 79 had pure-solid tumors. These two groups did not significantly differ in terms of clinical factors. However, the rates for PD-L1 positivity (4% vs. 25%, p < 0.01) and high PD-L1+ TPS (2% vs. 16%, p = 0.02) were significantly higher in the pure-solid tumors. The multivariate analyses (logistic regression model) showed that the odds ratios for PD-L1 positivity and high PD-L1+ TPS in pure-solid LADs were 5.9 (95% CI; 1.2–29.7) and 8.0 (95% CI; 1.0–63.8), respectively. In conclusion, LADs with GGO were correlated with a lower incidence of PD-L1 expression than pure-solid tumors.

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“…However, it has a high false‐positive rate (Gopal et al , ), and annual CT scans cause harmful radiation exposure (Bach et al , ). High‐risk groups also need to be better defined to increase screening effectiveness (Osarogiagbon et al , ). Therefore, there is a pressing need to understand the molecular changes occurring prior to disease to be able to develop noninvasive biomarkers of LC.…”

Section: Introductionmentioning

confidence: 99%

A 10‐year prediagnostic follow‐up study shows that serum RNA signals are highly dynamic in lung carcinogenesis

et al. 2020

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The majority of lung cancer (LC) patients are diagnosed at a late stage, and survival is poor. Circulating RNA molecules are known to have a role in cancer; however, their involvement before diagnosis remains an open question. In this study, we investigated circulating RNA dynamics in prediagnostic LC samples, focusing on smokers, to identify if and when diseaserelated signals can be detected in serum. We sequenced small RNAs in 542 serum LC samples donated up to 10 years before diagnosis and 519 matched cancer-free controls coming from 905 individuals in the Janus Serum Bank. This sample size provided sufficient statistical power to independently analyze time to diagnosis, stage, and histology. The results showed dynamic changes in differentially expressed circulating RNAs specific to LC histology and stage. The greatest number of differentially expressed RNAs was identified around 7 years before diagnosis for earlystage LC and 1-4 years prior to diagnosis for locally advanced and advanced-stage LC, regardless of LC histology. Furthermore, NSCLC and SCLC histologies have distinct prediagnostic signals. The majority of differentially expressed RNAs were associated with cancer-related pathways. The dynamic RNA signals pinpointed different phases of tumor development over time. Stage-specific RNA profiles may be associated with tumor aggressiveness. Our results improve the molecular understanding of carcinogenesis. They indicate substantial opportunity for screening and improved treatment and will guide further research on early detection of LC. However, the dynamic nature of the RNA signals also suggests challenges for prediagnostic biomarker discovery.

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Early-Stage NSCLC: Advances in Thoracic Oncology 2018

Cited by 44 publications

References 87 publications

Identification of an Immune Gene Expression Signature for Predicting Lung Squamous Cell Carcinoma Prognosis

Identification of an Immune Gene Expression Signature for Predicting Lung Squamous Cell Carcinoma Prognosis

Comparison of PD-L1 Expression Status between Pure-Solid Versus Part-Solid Lung Adenocarcinomas

A 10‐year prediagnostic follow‐up study shows that serum RNA signals are highly dynamic in lung carcinogenesis

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