scholarly journals Identification of potential diagnostic and therapeutic target genes for lung squamous cell carcinoma

2019 ◽  
Author(s):  
Nana Zhang ◽  
Hong Wang ◽  
Qiqi Xie ◽  
Hua Cao ◽  
Fanqi Wu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Therapeutic Target ◽  
Target Genes ◽  
Lung Squamous Cell Carcinoma

scholarly journals Circulating miR-16-5p, miR-92a-3p, and miR-451a in Plasma from Lung Cancer Patients: Potential Application in Early Detection and a Regulatory Role in Tumorigenesis Pathways

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2071 ◽  
Author(s):  
Patricia P. Reis ◽  
Sandra A. Drigo ◽  
Robson F. Carvalho ◽  
Rainer Marco Lopez Lapa ◽  
Tainara F. Felix ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Target Genes ◽  
Lung Squamous Cell Carcinoma ◽  
High Specificity ◽  
Mirna Signature ◽  
Lung Tumorigenesis ◽  
Lung Cancer Patients

Background: Micro(mi)RNAs, potent gene expression regulators associated with tumorigenesis, are stable, abundant circulating molecules, and detectable in plasma. Thus, miRNAs could potentially be useful in early lung cancer detection. We aimed to identify circulating miRNA signatures in plasma from patients with lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), and to verify whether miRNAs regulate lung oncogenesis pathways. Methods: RNA isolated from 139 plasma samples (40 LUAD, 38 LUSC; 61 healthy/non-diseased individuals) were divided into discovery (38 patients; 21 controls for expression quantification using an 800-miRNA panel; Nanostring nCounter®) and validation (40 patients; 40 controls; TaqMan® RT-qPCR) cohorts. Elastic net, Maximizing-R-Square Analysis (MARSA), and C-Statistics were applied for miRNA signature identification. Results: When compared to healthy individuals, 580 of 606 deregulated miRNAs in LUAD and 221 of 226 deregulated miRNAs in LUSC had significantly increased levels. Among the 10 most significantly overexpressed miRNAs, 6 were common to patients with LUAD and LUSC. Further analysis identified three signatures composed of 12 miRNAs. Signatures included miRNAs commonly overexpressed in patient plasma. Enriched pathways included target genes modulated by three miRNAs in the C-Statistics signature: miR-16-5p, miR-92a-3p, and miR-451a. Conclusions: The 3-miRNA signature (miR-16-5p, miR-92a-3p, miR-451a) had high specificity (100%) and sensitivity (84%) to predict cancer (LUAD and LUSC). These miRNAs are predicted to modulate genes and pathways with known roles in lung tumorigenesis, including EGFR, K-RAS, and PI3K/AKT signaling, suggesting that the 3-miRNA signature is biologically relevant in adenocarcinoma and squamous cell carcinoma of the lung.

scholarly journals TNIK is a therapeutic target in Lung Squamous Cell Carcinoma and regulates FAK activation through Merlin.

2021 ◽  
pp. candisc.0797.2020
Author(s):  
Pedro Torres-Ayuso ◽  
Elvira An ◽  
Katherine M. Nyswaner ◽  
Ryan C Bensen ◽  
Daniel A. Ritt ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Therapeutic Target ◽  
Lung Squamous Cell Carcinoma

Role of FGF receptors as an emerging therapeutic target in lung squamous cell carcinoma

2013 ◽  
Vol 9 (3) ◽  
pp. 377-386 ◽  
Author(s):  
Sun Min Lim ◽  
Hye Ryun Kim ◽  
Hyo Sup Shim ◽  
Ross A Soo ◽  
Byoung Chul Cho
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Therapeutic Target ◽  
Lung Squamous Cell Carcinoma

Identification of SLC38A7 as a Prognostic Marker and Potential Therapeutic Target of Lung Squamous Cell Carcinoma

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Naoki Haratake ◽  
Qingjiang Hu ◽  
Tatsuro Okamoto ◽  
Tomoko Jogo ◽  
Gouji Toyokawa ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Prognostic Marker ◽  
Squamous Cell ◽  
Therapeutic Target ◽  
Lung Squamous Cell Carcinoma ◽  
Potential Therapeutic Target

scholarly journals Clinical Value and Potential Mechanism of miRNA-33a-5p in Lung Squamous Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Xiang-Ming Wang ◽  
Shang-Wei Chen ◽  
Gang Chen ◽  
Hua-Fu Zhou ◽  
Ting-Qing Gan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Target Genes ◽  
Lung Squamous Cell Carcinoma ◽  
Functional Enrichment ◽  
Ppi Network ◽  
Summary Receiver Operating Characteristic ◽  
Potential Target ◽  
Standard Mean Difference

This study is aimed at thoroughly exploring the expression status, clinical significance, and underlying molecular mechanism of miRNA-33a-5p in lung squamous cell carcinoma (LUSC). Here, we detected miRNA-33a-5p in 20 samples from patients with LUSCs and 20 matching non-LUSC specimens by in-house quantitative real-time PCR (RT-qPCR). Relationship between miRNA-33a-5p expression and clinicopathological traits was investigated from materials derived from miRNA sequencing and miRNA microarrays. A pool standard mean difference (SMD) and summary receiver operating characteristic curves (SROC) were calculated to evaluate the integrated expression value of miRNA-33a-5p in LUSC. Twelve online platforms were applied to select potential target genes of miRNA-33a-5p. The differentially expressed genes (DEGs) of LUSC and the candidate target genes of miRNA-33a-5p were overlapped to acquire a set of specific genes for further analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and protein–protein interaction (PPI) network. miRNA-33a-5p overexpressed in LUSC was supported by 706 LUSC and 261 non-LUSC samples gathering from RT-qPCR, miRNA-seq, and public miRNA microarrays. The pooled SMD was 0.56 (95% CI: -0.01-1.05), and the area under the curve (AUC) of the SROC was 0.78 (95% CI: 0.74-0.82). A total of 240 genes were identified as potential target genes of miRNA-33a-5p for functional enrichment analyses; the results suggested that these target genes may participate in several vital biological processes that promote the proliferation and progression of LUSC. miRNA-33a-5p may play an essential role in the occurrence and development of LUSC by targeting hub genes (ETS1, EDNRB, CYR61, and LRRK2) derived from the PPI network. In summary, our results indicated that miRNA-33a-5p may contribute as a prospective therapeutic target in LUSC.

scholarly journals Lung squamous cell carcinoma and lung adenocarcinoma differential gene expression regulation through pathways of Notch, Hedgehog, Wnt, and ErbB signalling

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Dorota Anusewicz ◽  
Magdalena Orzechowska ◽  
Andrzej K. Bednarek
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Target Genes ◽  
Gene Expression Regulation ◽  
Lung Squamous Cell Carcinoma ◽  
Lung Cancers ◽  
Downstream Signaling ◽  
Downstream Target ◽  
Lung Malignancies

AbstractLung malignancies comprise lethal and aggressive tumours that remain the leading cancer-related death cause worldwide. Regarding histological classification, lung squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD) account for the majority of cases. Surgical resection and various combinations of chemo- and radiation therapies are the golden standards in the treatment of lung cancers, although the five-year survival rate remains very poor. Notch, Hedgehog, Wnt and Erbb signalling are evolutionarily conserved pathways regulating pivotal cellular processes such as differentiation, proliferation, and angiogenesis during embryogenesis and post-natal life. However, to date, there is no study comprehensively revealing signalling networks of these four pathways in LUSC and LUAD. Therefore, the aim of the present study was the investigation profiles of downstream target genes of pathways that differ between LUSC and LUAD biology. Our results showed a few co-expression modules, identified through weighted gene co-expression network analysis (WGCNA), which significantly differentiated downstream signaling of Notch, ErbB, Hedgehog, and Wnt in LUSC and LUAD. Among co-expressed genes essential regulators of the cell cycle, DNA damage response, apoptosis, and proliferation have been found. Most of them were upregulated in LUSC compared to LUAD. In conclusion, identified downstream networks revealed distinct biological mechanisms underlying cancer development and progression in LUSC and LUAD that may diversify the clinical outcome of the disease.

scholarly journals Syntaxin binding protein 4 as a novel therapeutic target and an effective biomarker for better treatment selection in lung squamous cell carcinoma: A theranostic study

2020 ◽  
Author(s):  
Erkhem-Ochir Bilguun ◽  
Kyoichi Kaira ◽  
Reika Kawabata-Iwakawa ◽  
Susumu Rokudai ◽  
Kimihiro Shimizu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Therapeutic Target ◽  
Binding Protein ◽  
Disease Free Survival ◽  
Lung Squamous Cell Carcinoma ◽  
Prognostic Impact ◽  
Rna Seq ◽  
Novel Therapeutic

Abstract Background Lung squamous cell carcinoma (LSCC) remains a challenging disease to treat, and further improvements in prognosis are dependent upon the identification of LSCC-specific therapeutic biomarkers and/or targets. We previously found that Syntaxin Binding Protein 4 (STXBP4) plays a crucial role in lesion growth and, therefore, clinical outcomes in LSCC patients through regulation of tumor protein p63 (TP63) ubiquitination. Methods To clarify the potential of STXBP4 as a novel therapeutic target and/or a predictive biomarker of therapeutic response, we assessed its prognostic impact of the protein in 144 LSCC patients and examined whether its action pathway is distinct from those of currently used drugs in in vitro experiments including RNA-seq analysis through comparison with the other putative exploratory targets and/or markers. Results Kaplan–Meier analysis revealed that, along with ΔNp63 (an isoform of TP63) and vascular endothelial growth factor receptor 2 (VEGFR2), STXBP4 expression signified a worse prognosis in LSCC patients, both in terms of overall survival (OS, P = 0.002) and disease-free survival (DFS, P = 0.041). Multivariate analysis demonstrated STXBP4 to be an independent prognostic factor for poor DFS, while VEGFR2 (P < 0.001) and TP63 (ΔNp63, P < 0.05) were independent prognostic factors for poor OS. The action pathway of STXBP4 on suppression of TP63 (ΔNp63), which results in the and inhibits tumor growth, was unique: Ingenuity pathway analysis using the knowledge database and our RNA-seq analysis in human LSCC cell lines indicated that 35 pathways were activated or inactivated in association with STXBP4, but the action pathway of STXBP4 was distinct from those of other current drug targets: STXBP4, TP63 and KDR (VEGFR2 gene) formed a cluster independent from other target genes of tumor protein p53 (TP53), tubulin beta 3 (TUBB3), stathmin 1 (STMN1) and cluster of differentiation 274 (CD274: programmed cell death 1 ligand 1, PD-L1). STXBP4 itself appeared not to be a potent predictive marker of individual drug response, but we found that TP63, main action target of STXBP4, might be involved in drug resistance mechanisms of LSCC. Conclusion STXBP4 could afford a unique therapeutic target and a key to the development of precision medicine for LSCC patients.

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