Stathmin-1 Is a Useful Diagnostic Marker for High-Grade Lung Neuroendocrine Tumors

Shimizu, Kimihiro; Goto, Yusuke; Kawabata‐Iwakawa, Reika; Ohtaki, Yoichi; Nakazawa, Shozo; Yokobori, Takehiko; Obayashi, Kai; Kawatani, Natsuko; Yajima, Toshiki; Kaira, Kyoichi; Mogi, Akira; Hirato, Junko; Nishiyama, Masahiko; Shirabe, Ken

doi:10.1016/j.athoracsur.2019.02.040

Cited by 9 publications

(5 citation statements)

References 28 publications

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“…High STMN1 expression is also associated with cancer progression and chemoresistance in lung squamous cell carcinoma (28). Similar to our results, Shimizu et al reported that all 17 LCNEC samples expressed a high level of STMN1 in their study, indicating that STMN1 might be a potential diagnostic marker for high-grade lung neuroendocrine tumors (29). Second, we identified the Wnt signaling pathway, which plays a role in the development of lung cancer (30).…”

Section: Discussionsupporting

confidence: 89%

Identification of novel transcription factor-microRNA-mRNA co-regulatory networks in pulmonary large-cell neuroendocrine carcinoma

Cai¹,

Zeng²,

Zhou³

et al. 2021

Ann Transl Med

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Background: Large cell neuroendocrine carcinoma (LCNEC) of the lung is a rare neuroendocrine neoplasm. Previous studies have shown that microRNAs (miRNAs) are widely involved in tumor regulation through targeting critical genes. However, it is unclear which miRNAs play vital roles in the pathogenesis of LCNEC, and how they interact with transcription factors (TFs) to regulate cancer-related genes.Methods: To determine the novel TF-miRNA-target gene feed-forward loop (FFL) model of LCNEC, we integrated multi-omics data from Gene Expression Omnibus (GEO), Transcriptional Regulatory Relationships Unraveled by Sentence-Based Text Mining (TRRUST), Transcriptional Regulatory Element Database (TRED), and The experimentally validated microRNA-target interactions database (miRTarBase database). First, expression profile datasets for mRNAs (GSE1037) and miRNAs (GSE19945) were downloaded from the GEO database. Overlapping differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified through integrative analysis. The target genes of the FFL were obtained from the miRTarBase database, and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed on the target genes. Then, we screened for key miRNAs in the FFL and performed gene regulatory network analysis based on key miRNAs. Finally, the TF-miRNA-target gene FFLs were constructed by the hypergeometric test.Results: A total of 343 DEGs and 60 DEMs were identified in LCNEC tissues compared to normal tissues, including 210 down-regulated and 133 up-regulated genes, and 29 down-regulated and 31 upregulated miRNAs. Finally, the regulatory network of TF-miRNA-target gene was established. The key regulatory network modules included ETS1-miR195-CD36, TAOK1-miR7-1-3P-GRIA1, E2F3-miR195-CD36, and TEAD1-miR30A-CTHRC1. Conclusions:We constructed the TF-miRNA-target gene regulatory network, which is helpful for understanding the complex LCNEC regulatory mechanisms.

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Section: Discussionsupporting

confidence: 89%

Identification of novel transcription factor-microRNA-mRNA co-regulatory networks in pulmonary large-cell neuroendocrine carcinoma

Cai¹,

Zeng²,

Zhou³

et al. 2021

Ann Transl Med

View full text Add to dashboard Cite

show abstract

“…High STMN1 expression is also associated with cancer progression and chemoresistance in lung squamous cell carcinoma [28]. Similar to our results, Shimizu et al reported that all 17 LCNEC samples expressed a high level of STMN1 in their study, indicating that STMN1 might be a potential diagnostic marker for high-grade lung neuroendocrine tumors [29]. Second, Wnt signaling pathway.…”

Section: Discussionsupporting

confidence: 88%

Identification of Novel Transcription Factor-microRNA-mRNA Co-regulatory Networks in Pulmonary Large-cell Neuroendocrine Carcinomas

Cai

Zhang

2020

Preprint

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Background: Large-cell neuroendocrine carcinoma (LCNEC) of the lung is a rare neuroendocrine neoplasm. Previous studies have shown that microRNAs can be widely involved in tumor regulation through targeting critical genes. However, it is unclear about which miRNAs play vital roles in LCNEC’s pathogenesis and how they interact with transcription factors (TFs) to regulate the cancer-related genes. Methods: To clarify the new TFs-miRNA-target gene feed-forward loops (FFLs) model of LCNEC, we integrated multi-omics data from GEO, TRRUST, TRED, and miRTarBase database. First, expression profile datasets for mRNAs (GSE1037) and miRNAs (GSE19945) were downloaded from the GEO database. Overlapping differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified through integrative analysis. The target genes of the FFL being obtained from the mirTarBase database, the GO and KEGG functional enrichment analysis was performed on the target gene. Then, we screened for key miRNAs in the FFL and perform gene regulatory network analysis based on key miRNAs. Finally, the TF-miRNA-target gene FFLs were constructed by the hypergeometric test.Results: A total of 343 DEGs and 60 DEMs were identified in LCNECs compared to normal tissues, including 210 downregulated, 133 upregulated genes and 29 downregulated, 31 upregulated miRNAs. Additionally, 55 DEMs were predicted through miRanda, mirDB, and TargetScan to be associated with the LCNEC 77 key genes. Finally, ETS1-miR195-CD36 and E2F3-miR195-CD36 from the TF-miRNA-mRNA FFLs were constructed and are significantly enriched in focal adhesion, cytokine-receptor interaction, hematopoietic cell lineage, and transforming growth factor (TGF)-β signaling pathways. Survival analysis showed that the differential expression of the multi-effect factors ETS1, CD36, and hsa-miR-195 in the FFL significantly affected the survival time of LCNEC patients.Conclusion: In summary, we construct the TF-miRNA-target regulatory network, which is helpful to understand the complex LCNEC regulatory mechanisms. The expression difference of regulated multi-effect target factors ETS1, CD36, and hsa-miR-195 has a significant impact on the survival and development of LCNEC.

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“…Stathmin-1 is associated with malignancy in NSCLC and is used in the differential diagnosis with high-grade LNETs. Stathmin-1 is a protein responsible for cancer cell survival, used in the signal transduction of malignant cells, and found at high levels in high-grade lung neuroendocrine tumors (HG-LNETs), being used for differential diagnosis between NSCLC and SCLC and LCNEC (47).…”

Section: Biological Landscape Of Lung Neuroendocrine Tumors (Lnets)mentioning

confidence: 99%

Lung neuroendocrine tumors: A systematic literature review (Review)

et al. 2021

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Neuroendocrine tumors (NETs) can have multiple localizations in the human body however, most often, it appears in the in thorax at tracheobronchial tree and the thymus. NETs are a group of tumors with heterogenous malignancy that evolve from neuroendocrine cells, with the lung being the second target organ after the gastrointestinal tract. These rare tumors are usually asymptomatic and non-functional with little information regarding incidence in the specialty literature. The main purpose of this review, was the analysis of the available literature in all aspects while mainly focusing on molecular diagnosis data and secondly, by using this molecular landscape to establish a differentiation of lung neuroendocrine tumors (LNETs). By analyzing the literature, new data were revealed regarding histological evaluation, genetic aberrations, prognosis depending on the type of LNET and therapeutic options that derive from these. Efficient management of these tumors is essential in the handling of symptoms and increase in life expectancy, especially in patients with functional tumors. Histological differentiation of LNETs is important in establishing proper therapeutic options and prognosis. Combined types of LNETs remain a controversial topic of discussion regarding diagnosis and treatment, a topic on which further studies are required in order to improve diagnosis in this group of tumors with heterogenous malignancy. Contents1. Introduction 2. Materials and methods 3. Epidemiology 4. Classification 5. Precursor lesions 6. Clinical features 7. Tumor staging 8. Biological landscape of lung neuroendocrine tumors (LNETs) 9. Radiological diagnosis 10. Surgical treatment 11. Advanced LNETs therapy 12. Conclusions

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Stathmin-1 Is a Useful Diagnostic Marker for High-Grade Lung Neuroendocrine Tumors

Cited by 9 publications

References 28 publications

Identification of novel transcription factor-microRNA-mRNA co-regulatory networks in pulmonary large-cell neuroendocrine carcinoma

Identification of novel transcription factor-microRNA-mRNA co-regulatory networks in pulmonary large-cell neuroendocrine carcinoma

Identification of Novel Transcription Factor-microRNA-mRNA Co-regulatory Networks in Pulmonary Large-cell Neuroendocrine Carcinomas

Lung neuroendocrine tumors: A systematic literature review (Review)

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