Development and Validation of Nine-RNA Binding Protein Signature Predicting Overall Survival for Kidney Renal Clear Cell Carcinoma

Zhong, Weimin; Huang, Chaoqun; Lin, Jianqiong; Zhu, Maoshu; Zhong, Hongbin; Chiang, Mao-Hsiung; Chiang, Hao-Sen; Hui, Mei-Sau; Lin, Yao; Huang, Jian

doi:10.3389/fgene.2020.568192

Cited by 17 publications

(14 citation statements)

References 39 publications

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“…Although the expression of EXOSC5 has been studied in different cancers, there are limited reports about the clinical relevance and functional roles of EXOSC5 in solid tumors. Compared to normal tissues, increased expression of EXOSC5 was reported in many types of tumor cell lines, such as hematopoietic tumor, cervical carcinoma, melanoma, colon cancer cell and renal cell carcinoma [11,18]. Yang et al purified recombinant EXOSC5 monoclonal antibody and found specific serological responses in 10-33% of patients with melanoma, lung cancer and prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

EXOSC5 promotes proliferation of gastric cancer through regulating AKT/STAT3 signaling pathways

Chen¹,

Huang²,

Liu³

et al. 2022

J. Cancer

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Purpose: Exosome component 5 (EXOSC5) is a non-catalytic component of the RNA exosome complex, which is interacted with the Zinc-finger antiviral protein to degrade the target RNA and aberrantly expressed in various malignances. We explored the molecular mechanisms and biological roles by which EXOSC5 promotes the progression of GC. Methods: We used quantitative real-time PCR, Western blotting and immunohistochemistry to analyze EXOSC5 expression in GC samples. An GC organoid-based functional model was assessed, and cancer cell CCK-8 assay, colony formation assay and flow cytometry were performed to reveal the role of EXOSC5 in GC cell proliferation and tumorigenesis. In vivo, nude mice tumorigenesis assay were performed to explore the effects of EXOSC5 knockdown on growth of GC. The roles of EXOSC5 on AKT and STAT3 signaling pathways were measured by Western blot. Results: The expression of EXOSC5 was up-regulated in GC tissues and cell lines compared with normal group, and highly expressed EXOSC5 indicated a poorer clinical outcome for GC patients and was positively correlated with tumor size and TNM stage. EXOSC5 overexpression facilitated the growth of GC cells and organoids, while EXOSC5 downregulation inhibited proliferation and induced G1/S phase transition arrest. Moreover, mechanistic studies demonstrated that EXOSC5 increased cyclinD1 expression levels and decreasing the expression levels of p21 and p27 via regulation of the AKT and STAT3 pathway. Conclusion:The expression of EXOSC5 is upregulated and correlated with tumorigenesis and poor prognosis of GC. EXOSC5 increases GC proliferation partly through activating AKT and STAT3 pathways.

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Section: Discussionmentioning

confidence: 99%

EXOSC5 promotes proliferation of gastric cancer through regulating AKT/STAT3 signaling pathways

Chen¹,

Huang²,

Liu³

et al. 2022

J. Cancer

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“…Moreover, compared with other similar research, our hypoxia-immune-related prognostic model had better effectiveness. Zhong et al developed a prognostic model based on nine RNA-binding protein signatures, and the AUC values of this model were 0.71, 0.66, and 0.69, respectively, for 1-, 3-, and 5-year OS (Zhong et al, 2020). Xu et al constructed a prognostic risk model based on PPAR pathway-related genes.…”

Section: Discussionmentioning

confidence: 99%

“…Zhong et al . developed a prognostic model based on nine RNA-binding protein signatures, and the AUC values of this model were 0.71, 0.66, and 0.69, respectively, for 1-, 3-, and 5-year OS ( Zhong et al, 2020 ). Xu et al .…”

Section: Discussionmentioning

confidence: 99%

Identification of Hypoxia–Immune-Related Gene Signatures and Construction of a Prognostic Model in Kidney Renal Clear Cell Carcinoma

Bai

Chen

Yan

et al. 2022

Front. Cell Dev. Biol.

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Introduction: Kidney renal clear cell carcinoma (KIRC), a kind of malignant disease, is a severe threat to public health. Tracking the information of tumor progression and conducting a related dynamic prognosis model are necessary for KIRC. It is crucial to identify hypoxia–immune-related genes and construct a prognostic model due to immune interaction and the influence of hypoxia in the prognosis of patients with KIRC.Methods: The hypoxia and immune status of KIRC patients were identified by utilizing t-SNE and ImmuCellAI for gene expression data. COX and Lasso regression were used to identify some hypoxia–immune-related signature genes and further construct a prognostic risk model based on these genes. Internal and external validations were also conducted to construct a prognostic model. Finally, some potentially effective drugs were screened by the CMap dataset.Results: We found that high-hypoxia and low-immune status tend to induce poor overall survival (OS). Six genes, including PLAUR, UCN, PABPC1L, SLC16A12, NFE2L3, and KCNAB1, were identified and involved in our hypoxia–immune-related prognostic risk model. Internal verification showed that the area under the curve (AUC) for the constructed models for 1-, 3-, 4-, and 5-year OS were 0.768, 0.754, 0.775, and 0.792, respectively. For the external verification, the AUC for 1-, 3-, 4-, and 5-year OS were 0.768, 0.739, 0.763, and 0.643 respectively. Furthermore, the decision curve analysis findings demonstrated excellent clinical effectiveness. Finally, we found that four drugs (including vorinostat, fludroxycortide, oxolinic acid, and flutamide) might be effective and efficient in alleviating or reversing the status of severe hypoxia and poor infiltration of immune cells.Conclusion: Our constructed prognostic model, based on hypoxia–immune-related genes, has excellent effectiveness and clinical application value. Moreover, some small-molecule drugs are screened to alleviate severe hypoxia and poor infiltration of immune cells.

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“…RPL13 was highly expressed in gastrointestinal cancer and enhanced the proliferation of gastrointestinal cancer cells and may be a useful molecular marker of drug efficacy in gastrointestinal cancer (46). In kidney renal clear cell carcinoma (KRCCC), researchers found that RPL13 was associated with the prognosis of tumor patients (47). Huang found that RPL14 are frequently altered during tumorigenesis of esophageal squamous cell carcinomas (ESCC) and could be used for the early detection of ESCC (48).…”

Section: Discussionmentioning

confidence: 99%

Quantitative Proteomic Analysis of Plasma Exosomes to Identify the Candidate Biomarker of Imatinib Resistance in Chronic Myeloid Leukemia Patients

Zhao

Chen

et al. 2021

Front. Oncol.

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BackgroundImatinib (IM), a tyrosine kinase inhibitor (TKI), has markedly improved the survival and life quality of chronic myeloid leukemia (CML) patients. However, the lack of specific biomarkers for IM resistance remains a serious clinical challenge. Recently, growing evidence has suggested that exosome-harbored proteins were involved in tumor drug resistance and could be novel biomarkers for the diagnosis and drug sensitivity prediction of cancer. Therefore, we aimed to investigate the proteomic profile of plasma exosomes derived from CML patients to identify ideal biomarkers for IM resistance.MethodsWe extracted exosomes from pooled plasma samples of 9 imatinib-resistant CML patients and 9 imatinib-sensitive CML patients by ultracentrifugation. Then, we identified the expression levels of exosomal proteins by liquid chromatography-tandem mass spectrometry (LC-MS/MS) based label free quantification. Bioinformatics analyses were used to analyze the proteomic data. Finally, the western blot (WB) and parallel reaction monitoring (PRM) analyses were applied to validate the candidate proteins.ResultsA total of 2812 proteins were identified in plasma exosomes from imatinib-resistant and imatinib-sensitive CML patients, including 279 differentially expressed proteins (DEPs) with restricted criteria (fold change≥1.5 or ≤0.667, p<0.05). Compared with imatinib-sensitive CML patients, 151 proteins were up-regulated and 128 proteins were down-regulated. Bioinformatics analyses revealed that the main function of the upregulated proteins was regulation of protein synthesis, while the downregulated proteins were mainly involved in lipid metabolism. The top 20 hub genes were obtained using STRING and Cytoscape, most of which were components of ribosomes. Moreover, we found that RPL13 and RPL14 exhibited exceptional upregulation in imatinib-resistant CML patients, which were further confirmed by PRM and WB.ConclusionProteomic analysis of plasma exosomes provides new ideas and important information for the study of IM resistance in CML. Especially the exosomal proteins (RPL13 and RPL14), which may have great potential as biomarkers of IM resistance.

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Development and Validation of Nine-RNA Binding Protein Signature Predicting Overall Survival for Kidney Renal Clear Cell Carcinoma

Cited by 17 publications

References 39 publications

EXOSC5 promotes proliferation of gastric cancer through regulating AKT/STAT3 signaling pathways

EXOSC5 promotes proliferation of gastric cancer through regulating AKT/STAT3 signaling pathways

Identification of Hypoxia–Immune-Related Gene Signatures and Construction of a Prognostic Model in Kidney Renal Clear Cell Carcinoma

Quantitative Proteomic Analysis of Plasma Exosomes to Identify the Candidate Biomarker of Imatinib Resistance in Chronic Myeloid Leukemia Patients

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