The Prognostic and Clinicopathological Significance of IGF-1R in NSCLC: a Meta-Analysis

Zhao, Jun; Shi, Xuefeng; Wang, Tao; Ying, Chunhua; He, Shaojun; Chen, Yifei

doi:10.1159/000480655

Cited by 19 publications

(23 citation statements)

References 32 publications

(43 reference statements)

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“…2). Because post-transcriptional/translational modifications caused inconsistencies between mRNA and protein levels, further analysis of 18 prognosis-related mRNAs with literature review found that IGF1R, vimentin (VIM encoded), and MRP1 (ABCC1 encoded) were prognosis-related proteins in LSCC [43][44][45]. For MRP1, its high mRNA expression was associated better survival status (Fig.…”

Section: Ubiquitination Affects Lscc Patient's Outcome By Regulating mentioning

confidence: 99%

Label-free quantitative identification of abnormally ubiquitinated proteins as useful biomarkers for human lung squamous cell carcinomas

Chen²,

Zhuang

et al. 2020

EPMA Journal

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Background Ubiquitination is an important molecular event in lung squamous cell carcinoma (LSCC), which currently is mainly studied in nonsmall cell lung carcinoma cell models but lacking of ubiquitination studies on LSCC tissues. Here, we presented the ubiquitinated protein profiles of LSCC tissues to explore ubiquitination-involved molecular network alterations and identify abnormally ubiquitinated proteins as useful biomarkers for predictive, preventive, and personalized medicine (PPPM) in LSCC. Methods Anti-ubiquitin antibody-based enrichment coupled with LC-MS/MS was used to identify differentially ubiquitinated proteins (DUPs) between LSCC and control tissues, followed by integrative omics analyses to identify abnormally ubiquitinated protein biomarkers for LSCC. Results Totally, 400 DUPs with 654 ubiquitination sites were identified,, and motifs AX (1/2/3)-K* were prone to be ubiquitinated in LSCC tissues. Those DUPs were involved in multiple molecular network systems, including the ubiquitinproteasome system (UPS), cell metabolism, cell adhesion, and signal transduction. Totally, 44 hub molecules were revealed by protein-protein interaction network analysis, followed by survival analysis in TCGA database (494 LSCC patients and 20,530 genes) to obtain 18 prognosis-related mRNAs, of which the highly expressed mRNAs VIM and IGF1R were correlated with poorer prognosis, while the highly expressed mRNA ABCC1 was correlated with better prognosis. VIM-encoded protein vimentin and ABCC1-encoded protein MRP1 were increased in LSCC, which were all associated with poor prognosis. Proteasome-inhibited experiments demonstrated that vimentin and MRP1 were degraded through UPS. Quantitative ubiquitinomics found ubiquitination level was decreased in vimentin and increased in MRP1 in LSCC. These findings showed that the increased vimentin in LSCC might be derived from its decreased ubiquitination level and that the increased MRP1 in LSCC might be derived from its protein synthesis > degradation. GSEA and co-expression gene analyses revealed that VIM and Electronic supplementary material The online version of this article (

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Section: Ubiquitination Affects Lscc Patient's Outcome By Regulating mentioning

confidence: 99%

Label-free quantitative identification of abnormally ubiquitinated proteins as useful biomarkers for human lung squamous cell carcinomas

Chen²,

Zhuang

et al. 2020

EPMA Journal

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“…( Zhu et al, 2017 ) Some studies revealed that high expression of IGF-1R and loss of PTEN were associated with poor prognosis in NSCLC. ( Zhao J. et al, 2017 ; Zhao Y. et al, 2017 ) Although biomarkers and therapeutic targets found in NSCLC have made a great contribution to improving the diagnosis and treatment of NSCLC, due to the biological complexity and poor prognosis of NSCLC, more genetic information remains urgently needed to provide reference for precision medical treatment ( Riess et al, 2018 ; Xu et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of Candidate Biomarkers Correlated With the Pathogenesis and Prognosis of Non-small Cell Lung Cancer via Integrated Bioinformatics Analysis

Liu

et al. 2018

Front. Genet.

108

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Background and Objective: Non-small cell lung cancer (NSCLC) accounts for 80–85% of all patients with lung cancer and 5-year relative overall survival (OS) rate is less than 20%, so that identifying novel diagnostic and prognostic biomarkers is urgently demanded. The present study attempted to identify potential key genes associated with the pathogenesis and prognosis of NSCLC.Methods: Four GEO datasets (GSE18842, GSE19804, GSE43458, and GSE62113) were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between NSCLC samples and normal ones were analyzed using limma package, and RobustRankAggreg (RRA) package was used to conduct gene integration. Moreover, Search Tool for the Retrieval of Interacting Genes database (STRING), Cytoscape, and Molecular Complex Detection (MCODE) were utilized to establish protein–protein interaction (PPI) network of these DEGs. Furthermore, functional enrichment and pathway enrichment analyses for DEGs were performed by Funrich and OmicShare. While the expressions and prognostic values of top genes were carried out through Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan Meier-plotter (KM) online dataset.Results: A total of 249 DEGs (113 upregulated and 136 downregulated) were identified after gene integration. Moreover, the PPI network was established with 166 nodes and 1784 protein pairs. Topoisomerase II alpha (TOP2A), a top gene and hub node with higher node degrees in module 1, was significantly enriched in mitotic cell cycle pathway. In addition, Interleukin-6 (IL-6) was enriched in amb2 integrin signaling pathway. The mitotic cell cycle was the most significant pathway in module 1 with the highest P-value. Besides, five hub genes with high degree of connectivity were selected, including TOP2A, CCNB1, CCNA2, UBE2C, and KIF20A, and they were all correlated with worse OS in NSCLC. Conclusion: The results showed that TOP2A, CCNB1, CCNA2, UBE2C, KIF20A, and IL-6 may be potential key genes, while the mitotic cell cycle pathway may be a potential pathway contribute to progression in NSCLC. Further, it could be used as a new biomarker for diagnosis and to direct the synthesis medicine of NSCLC.

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“…36 Moreover, high expression of IGF-1 receptor is also significantly associated with poor prognosis in NSCLC. 37 These results may, to some degree, explain why lung cancer patients with DM have a significantly poorer prognosis than those without. However, in contrast, one study reported that DM could delay NSCLC progression by increasing the level of longlived proteins modified with advanced glycation end product, which could lead to beneficial effects.…”

Section: Discussionmentioning

confidence: 96%

“…Evidence has shown that increased serum hemoglobin A1c, C‐peptide, and IGF‐1 levels are significantly correlated with the development and progression of lung cancer . Moreover, high expression of IGF‐1 receptor is also significantly associated with poor prognosis in NSCLC . These results may, to some degree, explain why lung cancer patients with DM have a significantly poorer prognosis than those without.…”

Section: Discussionmentioning

confidence: 99%

Diabetes mellitus and survival of non‐small cell lung cancer patients after surgery: A comprehensive systematic review and meta‐analysis

et al. 2019

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Background Diabetes mellitus (DM) is one of the most common comorbidities in surgically treated non‐small cell lung cancer (NSCLC) patients and has a negative impact on short‐term outcomes. However, the impact of DM on long‐term survival of such patients remains controversial; therefore, we conducted a comprehensive updated meta‐analysis. Methods We systematically searched relevant studies in PubMed, Embase, Cochrane Library, and Web of Science up to 6 September 2018. Hazard ratios (HRs) for the impact of DM on overall survival (OS) and recurrence‐free survival (RFS) of patients with surgically treated NSCLC were extracted and analyzed using the STATA 12.0 package. Results We included 13 cohort studies consisting of 4343 patients (730 patients with DM and 3613 patients without) with surgically treated NSCLC. Meta‐analysis showed that patients with DM had significantly poorer OS (random effects: HR 1.30, 95% confidence interval 1.05–1.60; P = 0.016) than those without. However, with a limited sample size, there was no significant difference in RFS (random effects: HR 1.06, 95% confidence interval 0.71–1.58; P = 0.786) between patients with and without DM after surgical resection of NSCLC. Conclusion DM is an independent unfavorable prognostic factor for patients with surgically treated NSCLC. High‐quality studies with appropriate adjustment for confounding factors are needed to confirm our conclusions.

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The Prognostic and Clinicopathological Significance of IGF-1R in NSCLC: a Meta-Analysis

Cited by 19 publications

References 32 publications

Label-free quantitative identification of abnormally ubiquitinated proteins as useful biomarkers for human lung squamous cell carcinomas

Label-free quantitative identification of abnormally ubiquitinated proteins as useful biomarkers for human lung squamous cell carcinomas

Identification of Candidate Biomarkers Correlated With the Pathogenesis and Prognosis of Non-small Cell Lung Cancer via Integrated Bioinformatics Analysis

Diabetes mellitus and survival of non‐small cell lung cancer patients after surgery: A comprehensive systematic review and meta‐analysis

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