The clinical and prognostic significance of YWHAZ in non‐small–cell lung cancer patients: Immunohistochemical analysis

Deng, Yong; Zheng, Jingbin; Ma, Jiangang

doi:10.1002/jcb.27915

Cited by 17 publications

(13 citation statements)

References 37 publications

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“…As can be seen in Figure 3A and Figure 4A, YWHAZ expression was significantly correlated with overall survival at 60 months in LIHC (p = 0.0197) and LUAD (p = 0.016), and with disease-free survival at 60 months in BRCA (p = 0.0279) and LUAD (p = 0.016). We also conducted Kaplan-Meier survival analysis in Gene Expression Profiling Interactive Analysis (GEPIA) database with larger samples [77], determining that overall survival time was remarkably longer in LIHC (p = 0.016) and LUAD (p = 0.00023) with low YWHAZ expression ( Figure 3B) [24], which was consistent with the result of TCGA. However, there was no statistic difference of disease-free survival between high YWHAZ and low YWHAZ samples ( Figure 4B).…”

Section: Prognosissupporting

confidence: 76%

“…Deng Y et al reported that YWHAZ mRNA and protein expression was significantly higher in 152 non-small cell lung cancer (NSCLC) tissues compared to 30 noncancerous lung tissues by qRT-PCR and IHC [24]. Using western blot, Zhao G-Y et al also detected higher YWHAZ expression in 16 NSCLC tissues than in matched adjacent tissues [25].…”

Section: Lung Cancermentioning

confidence: 99%

“…In vitro, proliferation, migration/invasion and EMT were enhanced in lung cancer cells overexpressing YWHAZ [7,26,28], while silence of YWHAZ led to the opposite [24,27,29]. Immunoprecipitation and immunofluorescence analysis revealed that YWHAZ formed complex with Hsp27 protein, colocalizing in the cytoplasm of lung cancer cells [25].…”

Section: Lung Cancermentioning

confidence: 99%

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The role of YWHAZ in cancer: A maze of opportunities and challenges

Gan

Feng

2020

J. Cancer

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YWHAZ (also named 14-3-3ζ) is a central hub protein for many signal transduction pathways and plays a significant role in tumor progression. Accumulating evidences have demonstrated that YWHAZ is frequently up-regulated in multiple types of cancers and acts as an oncogene in a wide range of cell activities including cell growth, cell cycle, apoptosis, migration, and invasion. Moreover, YWHAZ was reported to be regulated by microRNAs (miRNAs) or long non-coding RNAs and exerted its malignant functions by targeting downstream molecules like protein kinase, apoptosis proteins, and metastasis-related molecules. Additionally, YWHAZ may be a potential biomarker of diagnosis, prognosis and chemoresistance in several cancers. Targeting YWHAZ by siRNA, shRNA or miRNA was reported to have great help in suppressing malignant properties of cancer cells. In this review, we perform literature and bioinformatics analysis to reveal the oncogenic role and molecular mechanism of YWHAZ in cancer, and discuss the potential clinical applications of YWHAZ concerning diagnosis, prognosis, and therapy in malignant tumors.

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Section: Prognosissupporting

confidence: 76%

Section: Lung Cancermentioning

confidence: 99%

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The role of YWHAZ in cancer: A maze of opportunities and challenges

Gan

Feng

2020

J. Cancer

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“…The tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) was identified in 55.9% of all patients’ combinations from all nine cancer types. This protein is present in high levels in different cancer cells and is associated with tumor cell proliferation, cell invasion and migration, and drug resistance (Nishimura et al, 2013; Hong et al, 2018; Deng et al, 2019). This protein target has prognostic potential, and its overexpression is associated with short OS time in non-squamous-cell lung carcinoma (Deng et al, 2019); its knockdown has suppressed tumorigenesis in ovarian cancer cells (Hong et al, 2018).…”

Section: Resultsmentioning

confidence: 99%

Signaling Complexity Measured by Shannon Entropy and Its Application in Personalized Medicine

et al. 2019

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Traditional approaches to cancer therapy seek common molecular targets in tumors from different patients. However, molecular profiles differ between patients, and most tumors exhibit inherent heterogeneity. Hence, imprecise targeting commonly results in side effects, reduced efficacy, and drug resistance. By contrast, personalized medicine aims to establish a molecular diagnosis specific to each patient, which is currently feasible due to the progress achieved with high-throughput technologies. In this report, we explored data from human RNA-seq and protein–protein interaction (PPI) networks using bioinformatics to investigate the relationship between tumor entropy and aggressiveness. To compare PPI subnetworks of different sizes, we calculated the Shannon entropy associated with vertex connections of differentially expressed genes comparing tumor samples with their paired control tissues. We found that the inhibition of up-regulated connectivity hubs led to a higher reduction of subnetwork entropy compared to that obtained with the inhibition of targets selected at random. Furthermore, these hubs were described to be participating in tumor processes. We also found a significant negative correlation between subnetwork entropies of tumors and the respective 5-year survival rates of the corresponding cancer types. This correlation was also observed considering patients with lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) based on the clinical data from The Cancer Genome Atlas database (TCGA). Thus, network entropy increases in parallel with tumor aggressiveness but does not correlate with PPI subnetwork size. This correlation is consistent with previous reports and allowed us to assess the number of hubs to be inhibited for therapy to be effective, in the context of precision medicine, by reference to the 100% patient survival rate 5 years after diagnosis. Large standard deviations of subnetwork entropies and variations in target numbers per patient among tumor types characterize tumor heterogeneity.

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“…At present, many studies have indicated that the 14-3-3 protein plays an oncogenic role in many kinds of tumors and inhibits apoptosis [20,[28][29][30]. Therefore, we focused on monitoring the expression level of apoptosis-related proteins after stable overexpression of LNK.…”

Section: Discussionmentioning

confidence: 99%

Adaptor protein LNK promotes anaplastic thyroid carcinoma cell growth via 14-3-3 ε/γ binding

et al. 2020

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Background: Rapid progression contributes to treatment failure in anaplastic thyroid carcinoma (ATC) patients. In a preliminary study, we demonstrated that some hematopoietic factors may be involved in the progression of ATC. The adaptor protein LNK, which is a negative regulator of hematopoietic cytokine signalling, has been studied extensively in malignant hematopoietic cells. However, there are few studies on LNK in solid tumours. Methods: Real-time PCR, immunohistochemistry (IHC) and western blot analysis of LNK were performed on ATC cells, differentiated thyroid cancer (DTC) cells and normal thyroid cells. In vitro assays (including pull-down, liquid chromatography-mass spectrometry (LC-MS), co-IP, MTT and colony formation) were performed to validate the effect of LNK on ATC progression and elucidate the molecular mechanisms. Results: Compared with DTC cells and normal thyroid cells, ATC cells exhibit overexpression of LNK. In addition, LNK overexpression results in increased proliferation of ATC cells. Conversely, LNK knockdown significantly suppresses ATC cell proliferation. LC-MS identified the 14-3-3 ε/γ protein as a LNK binding partner. Finally, the results indicate that LNK overexpression significantly enhances the anti-apoptotic ability of ATC cells via the Akt-NFκB-Bcl-2/Bcl-xL pathway and that the oncogenic effect of LNK largely depends on 14-3-3 ε/γ binding. Conclusions: The present study elucidated the important role of LNK in the growth of ATC opposite to its behaviour in the hematopoietic system and indicates that LNK is a potential target for the treatment of ATC.

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The clinical and prognostic significance of YWHAZ in non‐small–cell lung cancer patients: Immunohistochemical analysis

Cited by 17 publications

References 37 publications

The role of YWHAZ in cancer: A maze of opportunities and challenges

The role of YWHAZ in cancer: A maze of opportunities and challenges

Signaling Complexity Measured by Shannon Entropy and Its Application in Personalized Medicine

Adaptor protein LNK promotes anaplastic thyroid carcinoma cell growth via 14-3-3 ε/γ binding

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