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Elevated expression of ADAP2 is associated with aggressive behavior of human clear-cell renal cell carcinoma and poor patient survival

  • Author Footnotes
    † These authors have contributed equally to this work
    Yuanyuan Qiang
    Footnotes
    † These authors have contributed equally to this work
    Affiliations
    Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of National Key Laboratory, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia, 750001, China
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  • Author Footnotes
    † These authors have contributed equally to this work
    Xuhui Wang
    Footnotes
    † These authors have contributed equally to this work
    Affiliations
    Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of National Key Laboratory, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia, 750001, China
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  • Author Footnotes
    † These authors have contributed equally to this work
    Jiangwei Ding
    Footnotes
    † These authors have contributed equally to this work
    Affiliations
    Department of Emergency Medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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  • Ziqin Wang
    Affiliations
    Basic medical school, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia, 750001, China
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  • Bianli Li
    Affiliations
    Department of Emergency Medicine, General Hospital of Ningxia Medical University, Yinchuan, China
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  • Hui Ji
    Affiliations
    Basic medical school, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia, 750001, China
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  • Xue Zhang
    Affiliations
    Foreign Language Teaching Department of Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia, 750001, China
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  • Yong Yang
    Affiliations
    Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of National Key Laboratory, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia, 750001, China
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  • Kunmei Liu
    Affiliations
    Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of National Key Laboratory, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia, 750001, China
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  • Lianxiang Zhang
    Affiliations
    Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of National Key Laboratory, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia, 750001, China
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  • Shengmao Ma
    Correspondence
    Co-Corresponding author. 301 Zhengyuan north road, Yinchuan, Ningxia, 750001, China, Tel: +86-951-6980240; Fax: +86-951-6980240
    Affiliations
    Thoracic Surgery department of People's Hospital of Ningxia Hui Autonomous Region, 301 Zhengyuan north road, Yinchuan, Ningxia, 750001, China
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  • Di Zhao
    Correspondence
    Co-Corresponding author. 301 Zhengyuan north road, Yinchuan, Ningxia, 750001, China, Tel: +86-951-6980240; Fax: +86-951-6980240
    Affiliations
    Department of Respiratory Medcine, People's Hospital of Ningxia Hui Autonomous Region, 301 Zhengyuan north road, Yinchuan, Ningxia, 750001, China
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  • Guangyuan Lu
    Correspondence
    Corresponding author. Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation, Base of National Key Laboratory, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia, 750001
    Affiliations
    Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of National Key Laboratory, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia, 750001, China
    Search for articles by this author
  • Author Footnotes
    † These authors have contributed equally to this work
Published:August 05, 2022DOI:https://doi.org/10.1016/j.clgc.2022.08.003

      Abstract

      Clear cell renal cell carcinoma (ccRCC) is the most common and lethal cancer of the adult kidney. Integrative database analysis was performed to identify a novel candidate oncogene, ADAP2, that was upregulated in clear cell renal cell carcinoma (ccRCC). However, the role and molecular mechanism of ADAP2 in ccRCC occurrence and progression are still unclear. In this study, we first confirmed that ADAP2 mRNA was expressed at significantly higher levels in 23 pairs of ccRCC tissues than in normal kidney tissues (P<0.01). Immunohistochemical analysis of 298 ccRCC tissues revealed elevated ADAP2 expression as an independent unfavorable prognostic factor for the overall survival (P =0.0042) and progression-free survival (P=0.0232) of patients. The Kaplan–Meier survival curve showed that patients with a higher expression of ADAP2 showed a significantly lower overall survival rate and disease-free survival rate. Moreover, high expression of ADAP2 at the mRNA level was associated with a worse prognosis for overall survival (P=0.0083) in The Cancer Genome Atlas (TCGA) cohort. A functional study showed that overexpression of ADAP2 promotes ccRCC cell proliferation and metastasis ability in vivo, whereas knockdown of ADAP2 inhibited cell proliferation, colony formation, migration and invasion in vitro. All results indicate that overexpression of ADAP2 is significantly related to tumor progression and could be an efficient way of predicting the prognosis of patients with ccRCC.

      Keywords

      Abbreviations:

      ccRCC (Clear cell renal cell carcinoma), OS (Overall survival), PFS (Progression-free survival), EMT (Epithelial-mesenchymal transition), FBS (Fetal bovine serum), PCR (Polymerase chain reaction), IHC (Immuno-histochemical), H&E (Hematoxylin and eosin), RNAi (RNA interference)
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