Tumor Spread Through Air Spaces Is a Survival Predictor in Non–Small-Cell Lung Cancer

Wang, Shuai; Hao, Jiatao; Qian, Cheng; Wang, Hao

doi:10.1016/j.cllc.2019.05.012

Cited by 27 publications

(20 citation statements)

References 28 publications

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“…5 Several meta-analyses have also been conducted based on the above-reported data, and the pooled results revealed that the presence of STAS suggested worse prognosis in non-small cell lung cancer collectively. 11,29,30 In IMA, the incidence of STAS was from 56.1% to 72.3%. IMA with STAS represented older age and absence of peripheral ground-glass opacity (GGO) on computed tomography (CT).…”

Section: Clinicopathologic Features and Prognosis Of Stasmentioning

confidence: 99%

<p>Spread Through Air Spaces (STAS) in Lung Cancer: A Multiple-Perspective and Update Review</p>

Meng¹,

Yu²,

Gao³

et al. 2020

CMAR

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Background: Spread through air spaces (STAS) is a spreading phenomenon of lung cancers, which is defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. To date, several articles have reviewed the studies concerning the significance of STAS; however, most articles focused on the prognosis without summarizing the significance of STAS on other aspects. In this review, we comprehensively summarized the current literature related to STAS, so as to explore the clinical significance of STAS from multiple perspectives. Main Body: This section provided a comprehensive overview of the significance of STAS from multiple perspectives and summarized current controversies and challenges in the diagnosis and clinical application. Conclusion: STAS is a conspicuous spreading phenomenon of lung cancers indicating worse prognosis; nevertheless, the treatment strategy for patients with STAS remains to be discussed. Further studies are needed to elaborate whether a STAS-positive patient who underwent limited resection needs a second operation or postoperative adjuvant treatment. Meanwhile, the internal mechanism of STAS formation is largely undiscovered. Whether the capability of detachment-migration-reattachment in STAS tumor cells is achieved at the time of primary tumorigenesis or in the progress of tumor development needs to be studied, and the related signal pathways or genetic alterations need to be explored. With this information, it may be possible to improve the prognosis of patients with STAS-positive lung cancers.

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Section: Clinicopathologic Features and Prognosis Of Stasmentioning

confidence: 99%

<p>Spread Through Air Spaces (STAS) in Lung Cancer: A Multiple-Perspective and Update Review</p>

Meng¹,

Yu²,

Gao³

et al. 2020

CMAR

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“…Mutated Kras driven murine lung tumors are considered to be weakly, if at all, invasive and it has been discussed that additional deletion of Tp53 is required for a full stromal invasive growth [ 14 , 25 ]. An alternative highly aggressive pathway for invasion in humans involves the spread of tumor cells via air spaces (STAS), for example presenting with micropapillary growth pattern associated with poor survival probability [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Notch1 Deficiency Induces Tumor Cell Accumulation Inside the Bronchiolar Lumen and Increases TAZ Expression in an Autochthonous KrasLSL-G12V Driven Lung Cancer Mouse Model

Meder

Florin

Ozretić

et al. 2021

Pathol. Oncol. Res.

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Purpose: Abrogation of Notch signaling, which is pivotal for lung development and pulmonary epithelial cell fate decisions was shown to be involved in the aggressiveness and the differentiation of lung carcinomas. Additionally, the transcription factors YAP and TAZ which are involved in the Hippo pathway, were recently shown to be tightly linked with Notch signaling and to regulate the cell fate in epidermal stem cells. Thus, we aim to elucidate the effects of conditional Notch1 deficiency on carcinogenesis and TAZ expression in lung cancer.Methods: We investigated the effect of conditional Cre-recombinase mediated Notch1 knock-out on lung cancer cells in vivo using an autochthonous mouse model of lung adenocarcinomas driven by KrasLSL-G12V and comprehensive immunohistochemical analysis. In addition, we analyzed clinical samples and human lung cancer cell lines for TAZ expression and supported our findings by publicly available data from The Cancer Genome Atlas (TCGA).Results: In mice, we found induction of papillary adenocarcinomas and protrusions of tumor cells from the bronchiolar lining upon Notch1 deficiency. Moreover, the mutated Kras driven lung tumors with deleted Notch1 showed increased TAZ expression and focal nuclear translocation which was frequently observed in human pulmonary adenocarcinomas and squamous cell carcinomas of the lung, but not in small cell lung carcinomas. In addition, we used data from TCGA to show that putative inactivating NOTCH1 mutations co-occur with KRAS mutations and genomic amplifications in lung adenocarcinomas.Conclusion: Our in vivo study provides evidence that Notch1 deficiency in mutated Kras driven lung carcinomas contributes to lung carcinogenesis in a subgroup of patients by increasing TAZ expression who might benefit from TAZ signaling blockade.

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“…Consequently, with the updated studies reporting its prognostic value in clinical practice, it is also the time for us to explore its mechanisms leading to worse survival. Wang S et al 21 have confirmed that STAS was associated with multiple aggressive characteristics. Among them, pleural invasion and vascular invasion have been defined as kinds of lung cancer invasion 22,23 .…”

Section: Publication Bias and Sensitivity Analysismentioning

confidence: 90%

Spread through air spaces is a poor prognostic indicator in patients undergoing lobectomy for lung cancer: A systematic review and meta-analysis

Wen¹,

Liang²,

Qiu³

et al. 2020

Preprint

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KEYWORDS 2 lung cancer, spread through air spaces, lobectomy, prognosis, meta-analysis 3 Abstract Background: Previous studies have confirmed the poor prognostic value of spread through air spaces (STAS) in patients undergoing limited resection for lung cancer. Nevertheless, its prognostic value remains controversial in patients undergoing lobectomy. Consequently, we aim to systematically and comprehensively evaluate the prognosis of patients with STAS undergoing lobectomy for lung cancer. Methods: An extensive search of literature databases was conducted. Recurrence-free survival (RFS) and overall survival (OS) were compared between patients with or without STAS undergoing lobectomy. In addition, results of the limited resection were also evaluated and presented. Results: 5 studies with 1531 patients reported the outcomes of lobectomy and 4 studies including 505 patients evaluated the survival of limited resection. In patients undergoing lobectomy, STAS was associated with significantly worse survival than non-STAS, including both RFS (HR=1.700; 95% CI: 1.265-2.283; P 0.001; P for heterogeneity=0.637; I2=0.0%) and OS (HR=2.620; 95% CI:1.138-6.031; P=0.024; P for heterogeneity=0.128; I2=51.4%). STAS was also correlated with shorter RFS (HR=3.434, 95%CI 2.173 to 5.428; P 0.001; P for heterogeneity=0.828, I2=0.0%) and OS (HR=3.494, 95%CI 2.128 to 5.736; P 0.001; P for heterogeneity=0.501, I2=0.0%) in limited resection.Conclusions: STAS is a poor prognostic indicator in patients undergoing lobectomy for lung cancer.

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Tumor Spread Through Air Spaces Is a Survival Predictor in Non–Small-Cell Lung Cancer

Cited by 27 publications

References 28 publications

<p>Spread Through Air Spaces (STAS) in Lung Cancer: A Multiple-Perspective and Update Review</p>

<p>Spread Through Air Spaces (STAS) in Lung Cancer: A Multiple-Perspective and Update Review</p>

Notch1 Deficiency Induces Tumor Cell Accumulation Inside the Bronchiolar Lumen and Increases TAZ Expression in an Autochthonous KrasLSL-G12V Driven Lung Cancer Mouse Model

Spread through air spaces is a poor prognostic indicator in patients undergoing lobectomy for lung cancer: A systematic review and meta-analysis

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