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Research ArticleOriginal Article
Open Access

BOLA family genes are the drivers and potential biomarkers of survival in kidney renal clear cell carcinoma patients

Mohammed Alissa, Abdullah Alghamdi, Suad A. Alghamdi, Mohammed A. Alshehri, Meshari A. Alsuwat, Mamdouh Allahyani and Ali G. Alkhathami
Saudi Medical Journal November 2024, 45 (11) 1207-1218; DOI: https://doi.org/10.15537/smj.2024.45.11.20240604
Mohammed Alissa
From the Department of Medical Laboratory (Alissa, A. Alghamdi, S. A. Alghamdi, Alshehri), College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, from the Department of Clinical Laboratory Sciences (Alsuwat, Allahyani), College of Applied Medical Sciences, Taif University, Taif, and from the Department of Clinical Laboratory Sciences (Alkhathami), College of Applied Medical Sciences, King Khalid University, Abha, Kingdom of Saudi Arabia.
MSc, PhD
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  • ORCID record for Mohammed Alissa
  • For correspondence: [email protected]
Abdullah Alghamdi
From the Department of Medical Laboratory (Alissa, A. Alghamdi, S. A. Alghamdi, Alshehri), College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, from the Department of Clinical Laboratory Sciences (Alsuwat, Allahyani), College of Applied Medical Sciences, Taif University, Taif, and from the Department of Clinical Laboratory Sciences (Alkhathami), College of Applied Medical Sciences, King Khalid University, Abha, Kingdom of Saudi Arabia.
MSc, PhD
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Suad A. Alghamdi
From the Department of Medical Laboratory (Alissa, A. Alghamdi, S. A. Alghamdi, Alshehri), College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, from the Department of Clinical Laboratory Sciences (Alsuwat, Allahyani), College of Applied Medical Sciences, Taif University, Taif, and from the Department of Clinical Laboratory Sciences (Alkhathami), College of Applied Medical Sciences, King Khalid University, Abha, Kingdom of Saudi Arabia.
MSc, PhD
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Mohammed A. Alshehri
From the Department of Medical Laboratory (Alissa, A. Alghamdi, S. A. Alghamdi, Alshehri), College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, from the Department of Clinical Laboratory Sciences (Alsuwat, Allahyani), College of Applied Medical Sciences, Taif University, Taif, and from the Department of Clinical Laboratory Sciences (Alkhathami), College of Applied Medical Sciences, King Khalid University, Abha, Kingdom of Saudi Arabia.
MSc, PhD
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Meshari A. Alsuwat
From the Department of Medical Laboratory (Alissa, A. Alghamdi, S. A. Alghamdi, Alshehri), College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, from the Department of Clinical Laboratory Sciences (Alsuwat, Allahyani), College of Applied Medical Sciences, Taif University, Taif, and from the Department of Clinical Laboratory Sciences (Alkhathami), College of Applied Medical Sciences, King Khalid University, Abha, Kingdom of Saudi Arabia.
MSc, PhD
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Mamdouh Allahyani
From the Department of Medical Laboratory (Alissa, A. Alghamdi, S. A. Alghamdi, Alshehri), College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, from the Department of Clinical Laboratory Sciences (Alsuwat, Allahyani), College of Applied Medical Sciences, Taif University, Taif, and from the Department of Clinical Laboratory Sciences (Alkhathami), College of Applied Medical Sciences, King Khalid University, Abha, Kingdom of Saudi Arabia.
MSc, PhD
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Ali G. Alkhathami
From the Department of Medical Laboratory (Alissa, A. Alghamdi, S. A. Alghamdi, Alshehri), College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, from the Department of Clinical Laboratory Sciences (Alsuwat, Allahyani), College of Applied Medical Sciences, Taif University, Taif, and from the Department of Clinical Laboratory Sciences (Alkhathami), College of Applied Medical Sciences, King Khalid University, Abha, Kingdom of Saudi Arabia.
MSc, PhD
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  • Figure 1
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    Figure 1

    - Profiling the expression, promoter methylation, and receiver operating characteristic (ROC) analysis of BOLA1, BOLA2, and BOLA3 genes in kidney renal clear cell carcinoma (KIRC) and control cell lines. A) Real-time quantitative polymerase chain reaction-based expression profiling of BOLA1, BOLA2, and BOLA3 genes in KIRC and control cell lines. B) ROC curves based on gene expressions of BOLA1, BOLA2, and BOLA3. C) Bisulfite sequencing-based promoter methylation profiling of BOLA1, BOLA2, and BOLA3 genes in KIRC and control cell lines. D) ROC curves based on promoter methylation level of BOLA1, BOLA2, and BOLA3. ***p<0.001. KIRC: kidney renal clear cell carcinoma, AUC: area under the curve

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    Figure 2

    - Validation of BOLA1, BOLA2, and BOLA3 promoter methylation levels and mutational analysis in extended kidney renal clear cell carcinoma (KIRC) cohorts via the OncoDB, UALCAN, GSCA, and cBioPortal databases. A) Methylation analysis via the OncoDB database. B) Methylation analysis via the UALCAN database. C) Methylation analysis via the GSCA database. D-E) Frequency of genetic mutations in BOLA1, BOLA2, and BOLA3 across KIRC patients. F) Effect of the genetic mutations on the overall survival of the KIRC patients. *p<0.05.

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    Figure 3

    - Survival analysis and correlation of BOLA1, BOLA2, and BOLA3 expression with diverse immune and molecular subtypes of kidney renal clear cell carcinoma (KIRC). A) Effect of the up-regulated BOLA1, BOLA2, and BOLA3 on the overall survival (OS) of KIRC patients. B) Effect of the up-regulated BOLA1, BOLA2, and BOLA3 on the relapse-free (RFS) survival of KIRC patients. C) Correlation of BOLA1, BOLA2, and BOLA3 expression with diverse immune subtypes of KIRC. D) Correlation of BOLA1, BOLA2, and BOLA3 expression with diverse molecular subtypes of KIRC. P<0.05.

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    Figure 4

    - Gene enrichment analysis of BOLA1, BOLA2, and BOLA3 using the DAVID tool. A) Cellular component (CC) terms. B) Biological process (BP) terms. C) Molecular Function (MF) terms. D) Kyoto encyclopedia of genes and genomes (KEGG) terms. P<0.05.

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    Figure 5

    - Knockdown of BOLA1, BOLA2, and BOLA3 impairs the growth and metastatic potential and enhances wound healing ability of the 786-O cells. A-B) The transfection efficiency of BOLA1, BOLA2, and BOLA3 was checked using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses. C) 786-O control and transfected cells were analyzed for colony formation. D-F) Proliferation and wound healing assays. ***P-value of <0.001.

Tables

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    Table 1

    - Drugs associated with BOLA genes that were sourced from DrugBank.

    GenesDrugsEffectsReferencesGroups
    BOLA1EstradiolReduce expression of BOLA1 mRNAA21133Approved
    CyclosporineA21092
    QuercetinA23748
    BOLA2DasatinibIncrease expression of BOLA2 mRNAA21899Approved
    CyclosporineA21092
    BOLA3CyclosporineDecrease expression of BOLA3 mRNAA21092Approved
    AcetylcysteineA20441
    CannabidiolA21508

    mRNA: messenger ribonucleic acid

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    Saudi Medical Journal: 45 (11)
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    1 Nov 2024
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    BOLA family genes are the drivers and potential biomarkers of survival in kidney renal clear cell carcinoma patients
    Mohammed Alissa, Abdullah Alghamdi, Suad A. Alghamdi, Mohammed A. Alshehri, Meshari A. Alsuwat, Mamdouh Allahyani, Ali G. Alkhathami
    Saudi Medical Journal Nov 2024, 45 (11) 1207-1218; DOI: 10.15537/smj.2024.45.11.20240604

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    BOLA family genes are the drivers and potential biomarkers of survival in kidney renal clear cell carcinoma patients
    Mohammed Alissa, Abdullah Alghamdi, Suad A. Alghamdi, Mohammed A. Alshehri, Meshari A. Alsuwat, Mamdouh Allahyani, Ali G. Alkhathami
    Saudi Medical Journal Nov 2024, 45 (11) 1207-1218; DOI: 10.15537/smj.2024.45.11.20240604
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    Keywords

    • BOLA genes
    • carcinoma
    • prognostic biomarkers
    • gene expression regulation
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