Exploring Novel Genome Instability-associated lncRNAs and their Potential Function in Pan-Renal Cell Carcinoma

  • Authors: Zhu H.1, Zheng W.2, Chen H.3, Chen J.4, Lin F.5, Chen S.3, Xue X.5, Zheng Q.3, Liang M.6, Xu N.5, Chen D.7, Sun X.3
  • Affiliations:
    1. Department of Surgery,, First Affiliated Hospital of Fujian Medical University
    2. Department of Urology, Urology Research Institute, First Affiliated Hospital of Fujian Medical University
    3. Department of Urology, Urology Research Institute, The First Affiliated Hospital, Fujian Medical University
    4. Department of Urology, Urology Research Institute, The First Affiliated Hospital, Fujian Medical University,
    5. Department of Urology, Urology Research Institute,, The First Affiliated Hospital, Fujian Medical University
    6. Department of Anesthesiology, Anesthesiology Research Institute, The First Affiliated Hospital of Fujian Medical University
    7. Department of Urology, Urology Research Institute,, The First Affiliated Hospital, Fujian Medical University,
  • Issue: Vol 27, No 12 (2024)
  • Pages: 1788-1807
  • Section: Chemistry
  • URL: https://rjpbr.com/1386-2073/article/view/643975
  • DOI: https://doi.org/10.2174/0113862073258779231020052115
  • ID: 643975

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Full Text

Abstract

Objective:Genomic instability can drive clonal evolution, continuous modification of tumor genomes, and tumor genomic heterogeneity. The molecular mechanism of genomic instability still needs further investigation. This study aims to identify novel genome instabilityassociated lncRNAs (GI-lncRNAs) and investigate the role of genome instability in pan-Renal cell carcinoma (RCC).

Materials and Methods:A mutator hypothesis was employed, combining the TCGA database of somatic mutation (SM) information, to identify GI-lncRNAs. Subsequently, a training cohort (n = 442) and a testing cohort (n = 439) were formed by randomly dividing all RCC patients. Based on the training cohort dataset, a multivariate Cox regression analysis lncRNAs risk model was created. Further validations were performed in the testing cohort, TCGA cohort, and different RCC subtypes. To confirm the relative expression levels of lncRNAs in HK-2, 786-O, and 769-P cells, qPCR was carried out. Functional pathway enrichment analyses were performed for further investigation.

Results:A total of 170 novel GI-lncRNAs were identified. The lncRNA prognostic risk model was constructed based on LINC00460, AC073218.1, AC010789.1, and COLCA1. This risk model successfully differentiated patients into distinct risk groups with significantly different clinical outcomes. The model was further validated in multiple independent patient cohorts. Additionally, functional and pathway enrichment analyses revealed that GI-lncRNAs play a crucial role in GI. Furthermore, the assessments of immune response, drug sensitivity, and cancer stemness revealed a significant relationship between GI-lncRNAs and tumor microenvironment infiltration, mutational burden, microsatellite instability, and drug resistance.

Conclusions:In this study, we discovered four novel GI-lncRNAs and developed a novel signature that effectively predicted clinical outcomes in pan-RCC. The findings provide valuable insights for pan-RCC immunotherapy and shed light on potential underlying mechanisms.

About the authors

Hui-Xin Zhu

Department of Surgery,, First Affiliated Hospital of Fujian Medical University

Email: info@benthamscience.net

Wen-Cai Zheng

Department of Urology, Urology Research Institute, First Affiliated Hospital of Fujian Medical University

Email: info@benthamscience.net

Hang Chen

Department of Urology, Urology Research Institute, The First Affiliated Hospital, Fujian Medical University

Email: info@benthamscience.net

Jia-Yin Chen

Department of Urology, Urology Research Institute, The First Affiliated Hospital, Fujian Medical University,

Email: info@benthamscience.net

Fei Lin

Department of Urology, Urology Research Institute,, The First Affiliated Hospital, Fujian Medical University

Email: info@benthamscience.net

Shao-Hao Chen

Department of Urology, Urology Research Institute, The First Affiliated Hospital, Fujian Medical University

Email: info@benthamscience.net

Xue-Yi Xue

Department of Urology, Urology Research Institute,, The First Affiliated Hospital, Fujian Medical University

Email: info@benthamscience.net

Qing-Shui Zheng

Department of Urology, Urology Research Institute, The First Affiliated Hospital, Fujian Medical University

Email: info@benthamscience.net

Min Liang

Department of Anesthesiology, Anesthesiology Research Institute, The First Affiliated Hospital of Fujian Medical University

Email: info@benthamscience.net

Ning Xu

Department of Urology, Urology Research Institute,, The First Affiliated Hospital, Fujian Medical University

Email: info@benthamscience.net

Dong-Ning Chen

Department of Urology, Urology Research Institute,, The First Affiliated Hospital, Fujian Medical University,

Author for correspondence.
Email: info@benthamscience.net

Xiong-Lin Sun

Department of Urology, Urology Research Institute, The First Affiliated Hospital, Fujian Medical University

Author for correspondence.
Email: info@benthamscience.net

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