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Associations between LncRNA MALAT1 Polymorphisms and Lymph Node Metastasis in Prostate Cancer.

ABSTRACT: Current evidence elucidates that long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) could regulate genetic expression and play a crucial role in both the diagnosis and prognosis of prostate cancer. Single-nucleotide polymorphisms (SNPs) of MALAT1 could alter the oncogenesis in various cancers. However, the associations between MALAT1 SNPs and prostate cancer have barely been investigated to date. This study included 579 patients with prostate cancer who received robotic-assisted radical prostatectomy at Taichung Veterans General Hospital from 2012 to 2017. Three SNPs of MALAT1 were analyzed to identify the impacts of SNPs on the clinicopathologic features in Taiwanese prostate cancer. Our results show that patients with a polymorphic G allele at rs619586 had a significantly higher risk of being in an advanced Gleason grade group (AOR: 1.764; 95% CI: 1.011-3.077; p = 0.046). Moreover, individuals with at least one polymorphic A allele at MALAT1 rs1194338 in the PSA >10 ng/mL group were positively associated with node-positive prostate cancer. In conclusion, MALAT1 SNPs are significantly associated with the susceptibility to both advanced Gleason grade and nodal metastasis in prostate cancer. The presence of MALAT1 SNPs rs619586 and rs1194338 seems to enhance oncogenesis in prostate cancer.

SUBMITTER: Hu JC

PROVIDER: S-EPMC8468695 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Lymph node metastases and tumor characteristics predict breast cancer prognosis but correlate imperfectly with likelihood of metastatic relapse. Discovery of genetic polymorphisms affecting metastasis may improve identification of patients requiring aggressive adjuvant therapy to prevent recurrence. We investigated associations between several variants in the BRMS1 and SIPA1 metastasis-modifying genes and lymph node metastases, tumor subtype and grade, recurrence, disease-free survival, and overall survival. This cross-sectional and prospective prognostic analysis included 859 patients who received surgery for incident breast cancer at Roswell Park Cancer Institute, participated in the DataBank and BioRepository shared resource, and had DNA, clinical, and pathology data available for analysis. Genotyping for BRMS1 (rs11537993, rs3116068, and rs1052566) and SIPA1 (rs75894763, rs746429, rs3741378, and rs2306364) polymorphisms was performed using Sequenom(®) iPLEX Gold and Taqman(®) real-time PCR assays. Logistic and Cox proportional hazards regressions were used to estimate odds ratios (OR) and hazard ratios (HR), respectively. BRMS1 rs1052566 heterozygous individuals were more likely to have node-positive tumors (OR = 1.58, 95 % CI 1.13-2.23), although there was no dose-response relationship, and those with at least one variant allele were less likely to have the luminal B subtype (AG + AA: OR = 0.59, 95 % CI 0.36-0.98). BRMS1 rs3116068 was associated with increased likelihood of having the luminal B and the HER2-enriched tumor subtype (P trend = 0.03). Two SIPA1 SNPs, rs746429 and rs2306364, were associated with decreased risk of triple-negative tumors (P trend = 0.04 and 0.07, respectively). Presence of 8 or more risk alleles was associated with an increased likelihood of having a node-positive tumor (OR = 2.14, 95 % CI 1.18-3.36, P trend = 0.002). There were no significant associations with survival. Polymorphisms in metastasis-associated genes may be related to tumor characteristics and lymph node metastasis, but not survival. Future evaluation of metastasis-modifying gene variants is necessary to better understand the biology of metastasis.

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Associations between LncRNA MALAT1 Polymorphisms and Lymph Node Metastasis in Prostate Cancer.

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