IDEAS home Printed from https://ideas.repec.org/a/gam/jijerp/v19y2022i19p12471-d929948.html
   My bibliography  Save this article

Genetic Analysis Implicates Dysregulation of SHANK2 in Renal Cell Carcinoma Progression

Author

Listed:
  • Chi-Fen Chang

    (Department of Anatomy, School of Medicine, China Medical University, Taichung 406, Taiwan)

  • Shu-Pin Huang

    (Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
    Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
    Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
    Ph.D. Program in Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan)

  • Yu-Mei Hsueh

    (Department of Family Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
    Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan)

  • Jiun-Hung Geng

    (Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
    Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
    Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan)

  • Chao-Yuan Huang

    (Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 100, Taiwan)

  • Bo-Ying Bao

    (Department of Pharmacy, China Medical University, Taichung 406, Taiwan
    Sex Hormone Research Center, China Medical University Hospital, Taichung 404, Taiwan
    Department of Nursing, Asia University, Taichung 413, Taiwan)

Abstract

SH3 and multiple ankyrin repeat domains (SHANK) is a family of scaffold proteins that were first identified to be involved in balancing synaptic transmission via regulation of intracellular signalling crosstalk and have been linked to various cancers. However, the role of the SHANK genes in renal cell carcinoma (RCC) remains to be elucidated. In this study, we aimed to evaluate whether genetic variants in SHANK family genes affect the risk of RCC and survival of patients. A genetic association study was conducted using logistic regression and Cox regression analyses, followed by the correction for a false discovery rate (FDR), in 630 patients with RCC and controls. A pooled analysis was further performed to summarise the clinical relevance of SHANK gene expression in RCC. After adjustment for known risk factors and the FDR, the SHANK2 rs10792565 T allele was found to be associated with an increased risk of RCC (adjusted odds ratio = 1.79, 95% confidence interval = 1.32–2.44, p = 1.96 × 10 −4 , q = 0.030), whereas no significant association was found with RCC survival. A pooled analysis of 19 independent studies, comprising 1509 RCC and 414 adjacent normal tissues, showed that the expression of SHANK2 was significantly lower in RCC than in normal tissues ( p < 0.001). Furthermore, low expression of SHANK2 was correlated with an advanced stage and poor prognosis for patients with clear cell and papillary RCC. This study suggests that SHANK2 rs10792565 is associated with an increased risk of RCC and that SHANK2 may play a role in RCC progression.

Suggested Citation

  • Chi-Fen Chang & Shu-Pin Huang & Yu-Mei Hsueh & Jiun-Hung Geng & Chao-Yuan Huang & Bo-Ying Bao, 2022. "Genetic Analysis Implicates Dysregulation of SHANK2 in Renal Cell Carcinoma Progression," IJERPH, MDPI, vol. 19(19), pages 1-9, September.
    • Handle: RePEc:gam:jijerp:v:19:y:2022:i:19:p:12471-:d:929948
    as

    Download full text from publisher

    File URL: https://www.mdpi.com/1660-4601/19/19/12471/pdf
    Download Restriction: no
    File URL: https://www.mdpi.com/1660-4601/19/19/12471/
    Download Restriction: no
    ---><---

    References listed on IDEAS

    as
    1. Tuuli Lappalainen & Michael Sammeth & Marc R. Friedländer & Peter A. C. ‘t Hoen & Jean Monlong & Manuel A. Rivas & Mar Gonzàlez-Porta & Natalja Kurbatova & Thasso Griebel & Pedro G. Ferreira & Matthia, 2013. "Transcriptome and genome sequencing uncovers functional variation in humans," Nature, Nature, vol. 501(7468), pages 506-511, September.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Katharina T. Schmid & Barbara Höllbacher & Cristiana Cruceanu & Anika Böttcher & Heiko Lickert & Elisabeth B. Binder & Fabian J. Theis & Matthias Heinig, 2021. "scPower accelerates and optimizes the design of multi-sample single cell transcriptomic studies," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    2. Nava Ehsan & Bence M. Kotis & Stephane E. Castel & Eric J. Song & Nicholas Mancuso & Pejman Mohammadi, 2024. "Haplotype-aware modeling of cis-regulatory effects highlights the gaps remaining in eQTL data," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    3. Jun Inamo & Akari Suzuki & Mahoko Takahashi Ueda & Kensuke Yamaguchi & Hiroshi Nishida & Katsuya Suzuki & Yuko Kaneko & Tsutomu Takeuchi & Hiroaki Hatano & Kazuyoshi Ishigaki & Yasushi Ishihama & Kazu, 2024. "Long-read sequencing for 29 immune cell subsets reveals disease-linked isoforms," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    4. Zhao Wang & Qian Liang & Xinyi Qian & Bolang Hu & Zhanye Zheng & Jianhua Wang & Yuelin Hu & Zhengkai Bao & Ke Zhao & Yao Zhou & Xiangling Feng & Xianfu Yi & Jin Li & Jiandang Shi & Zhe Liu & Jihui Hao, 2023. "An autoimmune pleiotropic SNP modulates IRF5 alternative promoter usage through ZBTB3-mediated chromatin looping," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    5. Anneke Brümmer & Sven Bergmann, 2024. "Disentangling genetic effects on transcriptional and post-transcriptional gene regulation through integrating exon and intron expression QTLs," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    6. Chachrit Khunsriraksakul & Qinmengge Li & Havell Markus & Matthew T. Patrick & Renan Sauteraud & Daniel McGuire & Xingyan Wang & Chen Wang & Lida Wang & Siyuan Chen & Ganesh Shenoy & Bingshan Li & Xue, 2023. "Multi-ancestry and multi-trait genome-wide association meta-analyses inform clinical risk prediction for systemic lupus erythematosus," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    7. Yuichi Shiraishi & Ai Okada & Kenichi Chiba & Asuka Kawachi & Ikuko Omori & Raúl Nicolás Mateos & Naoko Iida & Hirofumi Yamauchi & Kenjiro Kosaki & Akihide Yoshimi, 2022. "Systematic identification of intron retention associated variants from massive publicly available transcriptome sequencing data," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    8. Hanae Sato & Robert H. Singer, 2021. "Cellular variability of nonsense-mediated mRNA decay," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    9. Hao Wang & Jiaxin Yang & Yu Zhang & Jianliang Qian & Jianrong Wang, 2022. "Reconstruct high-resolution 3D genome structures for diverse cell-types using FLAMINGO," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    10. Guanghao Qi & Benjamin J. Strober & Joshua M. Popp & Rebecca Keener & Hongkai Ji & Alexis Battle, 2023. "Single-cell allele-specific expression analysis reveals dynamic and cell-type-specific regulatory effects," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    11. Ashley Budu-Aggrey & Anna Kilanowski & Maria K. Sobczyk & Suyash S. Shringarpure & Ruth Mitchell & Kadri Reis & Anu Reigo & Reedik Mägi & Mari Nelis & Nao Tanaka & Ben M. Brumpton & Laurent F. Thomas , 2023. "European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    12. Yirong Shi & Yiwei Niu & Peng Zhang & Huaxia Luo & Shuai Liu & Sijia Zhang & Jiajia Wang & Yanyan Li & Xinyue Liu & Tingrui Song & Tao Xu & Shunmin He, 2023. "Characterization of genome-wide STR variation in 6487 human genomes," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    13. Chachrit Khunsriraksakul & Daniel McGuire & Renan Sauteraud & Fang Chen & Lina Yang & Lida Wang & Jordan Hughey & Scott Eckert & J. Dylan Weissenkampen & Ganesh Shenoy & Olivia Marx & Laura Carrel & B, 2022. "Integrating 3D genomic and epigenomic data to enhance target gene discovery and drug repurposing in transcriptome-wide association studies," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    14. Jianping Quan & Ming Yang & Xingwang Wang & Gengyuan Cai & Rongrong Ding & Zhanwei Zhuang & Shenping Zhou & Suxu Tan & Donglin Ruan & Jiajin Wu & Enqin Zheng & Zebin Zhang & Langqing Liu & Fanming Men, 2024. "Multi-omic characterization of allele-specific regulatory variation in hybrid pigs," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    15. Kensuke Yamaguchi & Kazuyoshi Ishigaki & Akari Suzuki & Yumi Tsuchida & Haruka Tsuchiya & Shuji Sumitomo & Yasuo Nagafuchi & Fuyuki Miya & Tatsuhiko Tsunoda & Hirofumi Shoda & Keishi Fujio & Kazuhiko , 2022. "Splicing QTL analysis focusing on coding sequences reveals mechanisms for disease susceptibility loci," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    16. Luchang Ming & Debao Fu & Zhaona Wu & Hu Zhao & Xingbing Xu & Tingting Xu & Xiaohu Xiong & Mu Li & Yi Zheng & Ge Li & Ling Yang & Chunjiao Xia & Rongfang Zhou & Keyan Liao & Qian Yu & Wenqi Chai & Sij, 2023. "Transcriptome-wide association analyses reveal the impact of regulatory variants on rice panicle architecture and causal gene regulatory networks," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    17. Ke Mao & Christelle Borel & Muhammad Ansar & Angad Jolly & Periklis Makrythanasis & Christine Froehlich & Justyna Iwaszkiewicz & Bingqing Wang & Xiaopeng Xu & Qiang Li & Xavier Blanc & Hao Zhu & Qi Ch, 2023. "FOXI3 pathogenic variants cause one form of craniofacial microsomia," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    18. Qingbo S. Wang & Ryuya Edahiro & Ho Namkoong & Takanori Hasegawa & Yuya Shirai & Kyuto Sonehara & Hiromu Tanaka & Ho Lee & Ryunosuke Saiki & Takayoshi Hyugaji & Eigo Shimizu & Kotoe Katayama & Masahir, 2022. "The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:gam:jijerp:v:19:y:2022:i:19:p:12471-:d:929948. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: MDPI Indexing Manager (email available below). General contact details of provider: https://www.mdpi.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.