YAP1 protein expression has variant prognostic significance in small cell lung cancer (SCLC) stratified by histological subtypes

Wang, Xin; Guo, Yongli; Liu, Li; Wei, Jiacong; Zhang, Jinyao; Xie, Tongji; Dong, Jiyan; Li, Junling; Xing, Puyuan; Yang, Lin

doi:10.1016/j.lungcan.2021.06.026

Cited by 14 publications

(9 citation statements)

References 36 publications

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“…Among the 14 included articles, 4 articles including 6 studies ( 14 , 15 , 23 , 28 ), and 10 articles ( 13 , 18 – 22 , 24 – 27 ) containing 13 studies reported the relationship between TAZ and YAP and the prognosis of patients with lung cancer, respectively. Three studies, including 350 cases, reported these associations concerning SCLC in the Chinese population ( 24 , 26 ), and the other 16 studies, including 857 cases, reported these relationships concerning NSCLC. Three studies were conducted in the Caucasian population ( 13 , 14 , 21 ), and the others were performed in the East Asian population.…”

Section: Resultsmentioning

confidence: 99%

The Hippo Signaling Core Components YAP and TAZ as New Prognostic Factors in Lung Cancer

et al. 2022

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BackgroundThe Hippo pathway is an essential signaling cascade that regulates cell and organ growth. However, there is no consensus about (i) the expression levels of the Hippo signaling core components yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) in lung cancer, especially in small cell lung cancer (SCLC), or (ii) their association with the prognosis of patients with SCLC.MethodsWe screened relevant articles and identified eligible studies in the PubMed, EMBASE, COCHRANE, and WanFang databases. A combined analysis was performed to investigate (i) the expression levels of the major effectors, YAP and TAZ, in lung cancer and its subsets and (ii) their prognostic role in lung cancer, especially in SCLC.ResultsIn total, 6 studies related to TAZ and 13 studies concerning YAP were enrolled in this meta-analysis. We found that high TAZ expression was significantly associated with poor overall survival (OS) of patients with non-small cell lung cancer (NSCLC) in the overall population [Ph < 0.001, crude hazard ratio (HR) = 1.629, 95% CI = 1.199–2.214 for TAZ expression; Ph = 0.029, adjusted HR = 2.127, 95% CI = 1.307–3.460 for TAZ], the Caucasian population (Ph = 0.043, crude HR = 1.233, 95% CI = 1.030–1.477 for TAZ expression), and the Asian population (Ph = 0.551, adjusted HR = 2.676, 95% CI = 1.798–3.982 for TAZ). Moreover, there was a significant negative association between YAP expression and an unsatisfactory survival of patients with lung cancer (Ph = 0.327, crude HR = 1.652, 95% CI = 1.211–2.253 for YAP expression) and patients with NSCLC [disease-free survival (DFS): Ph = 0.693, crude HR = 2.562, 95% CI = 1.876–3.499 for YAP expression; Ph = 0.920, crude HR = 2.617, 95% CI = 1.690–4.052 for YAP-mRNA; OS: Ph = 0.878, crude HR = 1.777, 95% CI = 1.233–2.562 for YAP expression], especially in the Asian population (DFS: Ph = 0.414, crude HR = 2.515, 95% CI = 1.755–3.063; OS: Ph = 0.712, crude HR = 1.772, 95% CI = 1.214–2.587). However, no association was observed in the multivariate combined analysis. High YAP expression was significantly associated with short OS of patients with SCLC in our combined multivariate analysis in the Asian population (Ph = 0.289, crude HR = 4.482, 95% CI = 2.182–9.209), but not with crude data (Ph = 0.033, crude HR = 1.654, 95% CI = 0.434–6.300).ConclusionThe Hippo pathway is involved in carcinogenesis and progression of NSCLC and SCLC, and high expression levels of YAP and TAZ are independent and novel prognostic factors for lung cancer.

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Section: Resultsmentioning

confidence: 99%

The Hippo Signaling Core Components YAP and TAZ as New Prognostic Factors in Lung Cancer

et al. 2022

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“…Second, co‐analysis of ASCL1/DLL3 expression using routine IHC staining provides evidence for selection of potential subgroups, which is more applicable for advanced patients (accounting for 80% SCLC patients in clinical practice) because of insufficient sample amount for further examination. Third, unlike the study by Furuta et al, 12 we enrolled pure SCLC samples for study (that is more representative of authentic SCLC features compared to combined SCLC) because both of our previous works based on clinicopathological analysis 13 and YAP1 expression 14 revealed the distinction between pure SCLC and combined SCLC, and the latter presented much more heterogenicity. Although the cell origin of combined SCLC remains unclear, SCLC components and non‐SCLC components in combined SCLC have been reported to share almost 75% common mutations and show similar genetic background, suggesting that the SCLC components and non‐SCLC components are derived from common precursors.…”

Section: Discussionmentioning

confidence: 99%

“…Analysis of both ASCL1 and DLL3 in SCLC patient samples has been only reported in one recent study, 12 which investigated 95 surgically resected SCLC samples, including combined SCLC. However, our recently published studies revealed distinct prognostic impact factors 13 and YAP1 protein expression between pure SCLC and combined SCLC 14 . This suggests that combined SCLC and pure SCLC might be different entities and present different targetable oncogenic pathways.…”

Section: Introductionmentioning

confidence: 89%

“…However, our recently published studies revealed distinct prognostic impact factors 13 and YAP1 protein expression between pure SCLC and combined SCLC. 14 This suggests that combined SCLC and pure SCLC might be different entities and present different targetable oncogenic pathways. Therefore, in this study, we enrolled a large scale of 247 surgically resected pure SCLC samples (without combined non-small cell lung cancer component).…”

Section: Introductionmentioning

confidence: 99%

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ASCL1 and DLL3 expressions and their clinicopathological implications in surgically resected pure small cell lung cancer: A study of 247 cases from the National Cancer Center of China

Dong

Liu

et al. 2021

Thoracic Cancer

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Objective Small cell lung cancer (SCLC) is one of the most aggressive malignancies characterized by neuroendocrine (NE) differentiation. The Delta‐like protein 3 (DLL3), as a direct downstream target of ASCL1, is involved in NE differentiation and carcinogenesis of SCLC. This study aims to investigate the relationship between ASCL1 and DLL3 expressions and their clinicopathological implications in SCLC. Methods A total of 247 surgically resected pure SCLC samples with limited clinical stage and follow‐up data were retrieved in this retrospective study. ASCL1 and DLL3 protein expression was detected by immunohistochemistry staining. The correlations between ASCL1 and DLL3 expressions, as well as their clinicopathological features, were analyzed by χ2 tests. Disease‐free survival (DFS) and overall survival (OS) in SCLC patients with ASCL1/DLL3 low and high expressions were compared by the Kaplan‐Meier method and log‐rank tests. Results ASCL1 high expression was detected in 105 (42.5%) patients. Its expression was positively correlated with the clinical stage (p = 0.02) and nerve invasion (p = 0.03). DLL3 high expression was observed in 188 (72.8%) patients and was correlated with vascular invasion (p = 0.04). ASCL1 expression was positively associated with DLL3 expression (p = 0.03). In addition, DLL3 expression has a strong correlation with the expression of thyroid transcription factor‐1 (TTF1) and conventional NE markers. Conclusion ASCL1 and DLL3 were highly expressed in SCLC tumor samples, and a positive correlation between these two markers was observed. Co‐analysis of ASCL1 and DLL3 may identify a distinct SCLC subgroup benefit from targeted therapy. Therefore, ASCL1 and DLL3 could be potential biomarkers served for the selection of related patients.

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“…Still, YAP1 has been reported as one of the key transcription factors for molecular subtypes [13] , although it is not validated in studies like Gay's [14] . Our previous study found that expression of YAP1 was significantly higher in combined SCLC than that of pure SCLC as well as an unfavorable prognostic factor for combined SCLC [15] . Genomic data indicated that LCENC could be divided into SCLC-like profile ( RB1/TP53 inactivation, MYCL amplification) and NSCLC-like profile (alteration in STK11, KEAP1, KRAS, and other RAS pathway genes) [16] , [17] , [18] .…”

Section: Introductionmentioning

confidence: 92%

Prognostic significance of YAP1 expression and its association with neuroendocrine markers in resected pulmonary large cell neuroendocrine carcinoma (LCNEC)

Sun¹,

Zhang²,

Dong³

et al. 2022

Translational Oncology

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YAP1 protein expression has variant prognostic significance in small cell lung cancer (SCLC) stratified by histological subtypes

Cited by 14 publications

References 36 publications

The Hippo Signaling Core Components YAP and TAZ as New Prognostic Factors in Lung Cancer

The Hippo Signaling Core Components YAP and TAZ as New Prognostic Factors in Lung Cancer

ASCL1 and DLL3 expressions and their clinicopathological implications in surgically resected pure small cell lung cancer: A study of 247 cases from the National Cancer Center of China

Prognostic significance of YAP1 expression and its association with neuroendocrine markers in resected pulmonary large cell neuroendocrine carcinoma (LCNEC)

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