ANALYSIS OF ASSOCIATION BETWEEN MALAT1 GENE RS619586-POLYMORPHISM AND DISEASE-FREE SURVIVAL IN KIDNEY CANCER AND BLADDER CANCER PATIENTS
Abstract
MALAT1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) is an oncogenic long non-coding RNA, the overexpression of which is detected in many types of malignant tumors, including urinary tract cancer, and is often correlated with tumor progression and poor prognosis. Specific polymorphic loci within the MALAT1 gene are known to be associated with the development of urinary tract cancer and their impact on patient survival. Therefore, the aim of our work was to study the distribution of the MALAT1 rs619586-genotypes and alleles in patients with clear cell renal cell carcinoma (CCRCC) and transitional cell carcinoma of the urinary bladder (TCCUB), and to evaluate the potential association of this genetic locus with patient survival.
Material and methods. The study included 342 individuals: 101 patients with ССRCC, 141 patients with TCCUB, and 100 cancer-free controls. Genotyping for the MALAT1 rs619586-locus was performed using real-time polymerase chain reaction (RT-PCR) with the TaqMan Assay C___1060479_10. Statistical analysis of the results was performed using the Prism (version 10.4.1) and R (version 4.4.2) software.
Results. In CCRCC patients, the minor G-allele of the MALAT1 rs619586-polymorphism was significantly more frequent than in the control group (P = 0.03). No significant difference was found in the allele distribution for this locus among TCCUB patients (P = 0.09). A significant difference in the distribution of rs619586 genotypes was observed between men with CCRCC and male controls: carriers of the minor G-allele were more common among affected men (P = 0.01). Furthermore, among women with TCCUB, carriers of the minor G-allele were more frequent compared to female controls (P = 0.01). Sex-specific differences in the rs619586 genotype distribution were also revealed within the TCCUB group: female patients carried the minor allele more frequently than male patients (P = 0.0001). A decrease in survival was demonstrated in CCRCC patients who were carriers of the minor G-allele compared with major allele homozygotes (P = 0.0101). No association was detected between the MALAT1 rs619586-genotype and the overall survival of TCCUB patients (P = 0.8479).
Conclusions. The minor G-allele of the MALAT1 rs619586-polymorphism is more frequent in CCRCC patients than in the control group. Furthermore, ССRCC patients carrying the G-allele exhibit lower survival rates compared to major allele homozygotes.
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Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin [Internet]. 2019 Jan [cited 2025 Sep 12];69(1):7-34. Available from: https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21551 https://doi.org/10.3322/caac.21551
Chi Y, Wang D, Wang J, Yu W, Yang J. Long non-coding RNA in the pathogenesis of cancers. Cells [Internet]. 2019 Sep 1 [cited 2025 Oct 15];8(9):1015. Available from: https://www.mdpi.com/2073-4409/8/9/1015 https://doi.org/10.3390/cells8091015
Sun Y, Ma L. New insights into long non-coding RNA MALAT1 in cancer and metastasis. Cancers (Basel) [Internet]. 2019 Feb 13 [cited 2025 Oct 25];11(2):216. Available from: https://www.mdpi.com/2072-6694/11/2/216 https://doi.org/10.3390/cancers11020216
Xu D, Wang W, Wang D, Ding J, Zhou Y, Zhang W. Long noncoding RNA MALAT-1: a versatile regulator in cancer progression, metastasis, immunity, and therapeutic resistance. Noncoding RNA Res [Internet]. 2024 Feb 1 [cited 2025 Sep 17];9(2):388-406. Available from: https://www.sciencedirect.com/science/article/pii/S2468054024000155?via%3Dihub https://doi.org/10.1016/j.ncrna.2024.01.015
Bitaraf A, Zafarani A, Jahandideh P, Hakak-Zargar B, Haghi A, Asgaritarghi G, et al. MALAT1 as a molecular driver of tumor progression, immune evasion, and resistance to therapy. Mol Cancer [Internet]. 2025 Oct 6 [cited 2025 Oct 25];24:245. Available from: https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-025-02415-6#citeas https://doi.org/10.1186/s12943-025-02415-6
Sheng XF, Hong LL, Li H, Huang FY, Wen Q, Zhuang HF. Long non-coding RNA MALAT1 modulate cell migration, proliferation and apoptosis by sponging microRNA-146a to regulate CXCR4 expression in acute myeloid leukemia. Hematology [Internet]. 2021 Dec [cited 2025 Sep 15];26(1):43-52. Available from: https://www.tandfonline.com/doi/10.1080/16078454.2020.1867781?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed https://doi.org/10.1080/16078454.2020.1867781
Wei Y, Niu B. Role of MALAT1 as a prognostic factor for survival in various cancers: a systematic review of the literature with meta-analysis. Dis Markers [Internet]. 2015 [cited 2025 Sep 29];2015:164635. Available from: https://onlinelibrary.wiley.com/doi/10.1155/2015/164635 https://doi.org/10.1155/2015/164635
Ying L, Chen Q, Wang Y, Zhou Z, Huang Y, Qiu F. Upregulated MALAT-1 contributes to bladder cancer cell migration by inducing epithelial-tomesenchymal transition. Mol Biosyst [Internet]. 2012 Sep [cited 2025 Oct 23];8(9):2289-94. Available from: https://pubs.rsc.org/en/content/articlelanding/2012/mb/c2mb25070e https://doi.org/10.1039/c2mb25070e
Xie H, Liao X, Chen Z, Fang Y, He A, Zhong Y, et al. LncRNA MALAT1 inhibits apoptosis and promotes invasion by antagonizing miR-125b in bladder cancer cells. J Cancer [Internet]. 2017 Oct 17 [cited 2025 Sep 17];8(18):3803-11. Available from: https://www.jcancer.org/v08p3803.htm https://doi.org/10.7150/jca.21228
Li C, Cui Y, Liu LF, Ren WB, Li QQ, Zhou X, et al. High expression of long noncoding RNA MALAT1 Iindicates a poor prognosis and promotes clinical progression and metastasis in bladder cancer. Clin Genitourin Cancer [Internet]. 2017 [cited 2025 Oct 14];15(5):570-6. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1558-7673(17)30125-8 https://doi.org/10.1016/j.clgc.2017.05.001
Krishnan S, Kanthaje S, Rekha PD, Mujeeburahiman M, Ratnacaram CK. Expanding frontiers in liquid biopsy-discovery and validation of circulating biomarkers in renal cell carcinoma and bladder cancer. Int Rev Cell Mol Biol [Internet]. 2025 [cited 2025 Oct 25];391:135-97. Available from: https://www.sciencedirect.com/science/article/pii/S1937644824001229?via%3Dihub https://doi.org/10.1016/bs.ircmb.2024.08.005
Zhang L, Zhou L, Xu W, Wu P, Chen W, Li H, et al. RNA m5C Modifications in the development and prognosis of muscle-invasive bladder cancer. Mol Carcinog [Internet]. 2025 Sep 25 [cited 2025 Oct 27]. Available from: https://onlinelibrary.wiley.com/doi/10.1002/mc.70042 https://doi.org/10.1002/mc.70042
Puri B, Majumder S, Gaikwad AB. LncRNA MALAT1 as a potential diagnostic and therapeutic target in kidney diseases. Pathol Res Pract [Internet]. 2025 Feb [cited 2025 Oct 13];266:155783. Available from: https://www.sciencedirect.com/science/article/pii/S0344033824006940?via%3Dihub https://doi.org/10.1016/j.prp.2024.155783
Goyal B, Yadav SRM, Awasthee N, Gupta S, Kunnumakkara AB, Gupta SC. Diagnostic, prognostic, and therapeutic significance of long non-coding RNA MALAT1 in cancer. Biochim Biophys Acta Rev Cancer [Internet]. 2021 Apr [cited 2025 Oct 25];1875(2):188502. Available from: https://www.sciencedirect.com/science/article/pii/S0304419X21000019?via%3Dihub https://doi.org/10.1016/j.bbcan.2021.188502
Volkogon AD, Roshchupkin AA, Chumachenko YD, Harbuzova VY, Ataman AV. Assotiation of MALAT1 rs3200401 gene polymorphism with kidney cancer in Ukrainian population. East. Ukr. Med [Internet]. 2019 Jun 28 [cited 2025 Sep 29];7(2):121-5. Available from: https://eumj.med.sumdu.edu.ua/index.php/journal/article/view/18 https://doi.org/10.21272/eumj.2019;7(2):121-125
Volkogon A, Kolnoguz O, Harbuzova V, Ataman A. Long non-coding RNA MALAT1 gene polymorphism is associated with disease-free survival in bladder cancer patients. Galician Med J [Internet]. 2020 Jun 30 [cited 2025 Oct 21];27(2):E202025. Available from: https://ifnmujournal.com/gmj/article/view/1133 https://doi.org/10.21802/gmj.2020.2.5
Volkohon AD, Chumachenko YD, Roshchupkin AA, Harbuzova VYu, Ataman AV. Association between rs3200401 long non-coding RNA MALAT1 gene polymorphism and bladder cancer development. Bukovinian Med Her [Internet]. 2019 Aug 29 [cited 2025 Sep 25];23(3(91)):23-7. Available from: http://e-bmv.bsmu.edu.ua/article/view/2413-0737.XXIII.3.91.2019.57 https://doi.org/10.24061/2413-0737.xxiii.3.91.2019.57. [In Ukrainian].
Powles T, Albiges L, Staehler M, Bensalah K, Dabestani S, Giles RH, et al. Updated European Association of Urology guidelines: recommendations for the treatment of first-line metastatic clear cell renal cancer. Eur Urol [Internet]. 2018 Mar [cited 2025 Sep 19];73(3):311-5. Available from: https://www.sciencedirect.com/science/article/pii/S0302283817310011?via%3Dihub https://doi.org/10.1016/j.eururo.2017.11.016
Ni W, Wang X, Sun Y, Gao X. Meta-analysis of the association between MALAT1 rs619586 A>G polymorphism and cancer risk. J Int Med Res [Internet]. 2020 Jul [cited 2025 Oct 14];48(7):300060520941969. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7388131/ https://doi.org/10.1177/0300060520941969
Cao L, Yan G, Yu S, Li F, Su Z, Hou X, et al. Associations of MALAT1 and its functional single nucleotide polymorphisms with cancer. Pathol Res Pract [Internet]. 2022 Aug [cited 2025 Oct 05];236:153988. Available from: https://www.sciencedirect.com/science/article/pii/S0344033822002321?via%3Dihub https://doi.org/10.1016/j.prp.2022.153988
Ji P, Diederichs S, Wang W, Böing S, Metzger R, Schneider PM, et al. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene [Internet]. 2003 Sep 11 [cited 2025 Sep 25];22:8031-41. Available from: https://www.nature.com/articles/1206928 https://doi.org/10.1038/sj.onc.1206928
National Library of Medicine. MALAT1 homo sapiens – SNP [Internet]. Available from: https://www.ncbi.nlm.nih.gov/snp/?term=MALAT1++homo+sapience
Sun YH, Chou YH, Tsai HY, Hsiao YH, Lee CY, Yang SF, et al. Impact of genetic variants of long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 on uterine cervical cancer. J Cancer [Internet]. 2022 Apr 4 [cited 2025 Oct 11];13(7):2150-8. Available from: https://www.jcancer.org/v13p2150.htm https://doi.org/10.7150/jca.70730
Tong G, Tong W, He R, Cui Z, Li S, Zhou B, et al. MALAT1 polymorphisms and lung cancer susceptibility in a Chinese Northeast Han population. Int J Med Sci [Internet]. 2022 Jul 11 [cited 2025 Oct 22];19(8):1300-6. Available from: https://www.medsci.org/v19p1300.htm https://doi.org/10.7150/ijms.73026
Hu JC, Wang SS, Chou YE, Chiu KY, Li JR, Chen CS, et al. Associations between LncRNA MALAT1 polymorphisms and lymph node metastasis in prostate cancer. Diagnostics (Basel) [Internet]. 2021 Sep 16 [cited 2025 Sep 25];11(9):1692. Available from: https://www.mdpi.com/2075-4418/11/9/1692 https://doi.org/10.3390/diagnostics11091692
Wang ML, Liu JX. MALAT1 rs619586 polymorphism functions as a prognostic biomarker in the management of differentiated thyroid carcinoma. J Cell Physiol [Internet]. 2020 Feb [cited 2025 Sep 22];235(2):1700-10. Available from: https://onlinelibrary.wiley.com/doi/10.1002/jcp.29089 https://doi.org/10.1002/jcp.29089. Retraction in: J Cell Physiol. 2022 May;237(5):2601. https://doi.org/10.1002/jcp.30742
Hong JH, Jin EH, Chang IA, Kang H, Lee SI, Sung JK. Association of long noncoding RNA MALAT1 polymorphisms with gastric cancer risk in Korean individuals. Mol Genet Genomic Med [Internet]. 2020 Dec [cited 2025 Oct 14];8(12):e1541. Available from: https://onlinelibrary.wiley.com/doi/10.1002/mgg3.1541 https://doi.org/10.1002/mgg3.1541
Gao XR, Wang XY, Li XY, Sun YQ, Zhang SL. Clinical significance and function of MALAT1 gene expression and the rs619586 polymorphism in colorectal cancer. Biomed Environ Sci [Internet]. 2022 Aug 20 [cited 2025 Oct 22];35(8):768-1. Available from: https://www.besjournal.com/en/article/doi/10.3967/bes2022.101 https://doi.org/10.3967/bes2022.101
Orlandi E, Zanot C, Poli A, Nicolis M, Rodolfo M, Turco A, et al. Lack of association of metastasis-associated lung adenocarcinoma transcript 1 variants with melanoma skin cancer risk. Melanoma Res [Internet]. 2019 Dec [cited 2025 Sep 25];29(6):660-3. Available from: https://journals.lww.com/melanomaresearch/abstract/2019/12000/lack_of_association_of_metastasis_associated_lung.14.aspx https://doi.org/10.1097/CMR.0000000000000605
Wang JZ, Xiang JJ, Wu LG, Bai YS, Chen ZW, Yin XQ, et al. A genetic variant in long non-coding RNA MALAT1 associated with survival outcome among patients with advanced lung adenocarcinoma: a survival cohort analysis. BMC Cancer [Internet]. 2017 Mar 3 [cited 2025 Sep 29];17:167. Available from: https://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3151-6 https://doi.org/10.1186/s12885-017-3151-6
Peng R, Luo C, Guo Q, Cao J, Yang Q, Dong K, et al. Association analyses of genetic variants in long non-coding RNA MALAT1 with breast cancer susceptibility and mRNA expression of MALAT1 in Chinese Han population. Gene [Internet]. 2018 Feb 5 [cited 2025 Oct 22];642:241-8. Available from: https://www.sciencedirect.com/science/article/pii/S0378111917309563?via%3Dihub https://doi.org/10.1016/j.gene.2017.11.013
Peresypkina TV, Butenko AI, Peresypkina AM. Determination of syntropy index for substantiation of measures for early diagnosis and prevention of non-communicable diseases. J V N Karazin Kharkiv Natl Univ Med. 2021;41:98–106. https://doi.org/10.26565/2313-6693-2021-41-11.
United Nations. Transforming our world: The 2030 agenda for sustainable development [Internet]. New York: United Nations; 2015. [cited 2024 Nov 27]. Available from: https://sdgs.un.org/goals.
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