Abstract
ObjectiveLncARSR (lncRNA Activated in RCC with Sunitinib Resistance, ENST00000424980) is a newly identified lncRNA to promote the sunitinib resistance of renal cell carcinoma (RCC), which may contribute to tumorigenesis and progression. This study aimed to explore the association of lncARSR tagSNPs with the risk and prognosis of RCC.MethodsIn this study, a 2‐stage case‐control study was performed to evaluate the association between 2 tagging SNPs (rs1417080 and rs7859384) and RCC susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by unconditional logistic regression analyses. Different survival time was estimated by the Kaplan‐Meier method and compared by the Log‐rank test. Hazard ratios (HRs) and their 95% CIs were calculated to determine predictive factors by Cox proportion hazards model.ResultsWhen combing discovery and validation sets together, rs7859384 was determined to be significantly associated with the decreased RCC risk with all P < 0.05 in 4 models (co‐dominant model, additive model, dominant model and recessive model). stratified analyses showed prominent risk effect of SNP rs7859384 GA/GG genotypes was found in clinical subgroups of stage I and stage II (P = 0.009, OR = 0.77, 95% CI = 0.64‐0.94) and individuals with clear cell RCC (P = 0.014, OR = 0.79, 95% CI = 0.65‐0.95). A protective effect of SNP rs7859384 GA/GG genotypes was observed among individuals with BMI > 24 (P = 0.025, OR = 0.74, 95% CI = 0.56‐0.96), without hypertension (P = 0.037, OR = 0.79, 95% CI = 0.63‐0.99), without family history of cancer (P = 0.048, OR = 0.83, 95% CI = 0.68‐1.00). Survival analyses revealed individuals with GA/GG genotypes had higher survival rate compared with the corresponding AA wild genotypes in the dominant model (log‐rank P = 0.005, adjusted HR = 0.34, 95% CI = 0.16‐0.73).ConclusionThis study suggests that rs7859384 of lncARSR was associated with RCC susceptibility and may act as a prognostic biomarker for patients with RCC.
Highlights
An estimated 65,340 Americans were diagnosed with renal malignancy and 14,970 died of the disease in 2018.1 Renal cell carcinoma (RCC) is the most common renal malignancy accounting for 90% of the subtypes and approximately 80% of tumors are clear cell renal cell carcinoma.[2,3] In clinical therapy, surgical resection is just an effective treatment for localized tumor, but the disease still exhibits substantial mortality due to regional or distant metastasis 4 with a characteristic of high resistance toward conventional chemotherapy a radiotherapy.[5]
A protective effect of SNP rs7859384 GA/GG genotypes was observed among individuals with body mass index (BMI) > 24 (P = 0.025, Odds ratios (ORs) = 0.74, 95% confidence intervals (CIs) = 0.56‐0.96), without hypertension (P = 0.037, OR = 0.79, 95% CI = 0.63‐0.99), without family history of cancer (P = 0.048, OR = 0.83, 95% CI = 0.68‐1.00)
Our study revealed that rs7859384 variant GA/GG genotypes in lncARSR was associated with a decreased risk of RCC while rs1417080 variant TC/CC genotypes did not show a significant relationship with the risk of RCC
Summary
An estimated 65,340 Americans were diagnosed with renal malignancy and 14,970 died of the disease in 2018.1 Renal cell carcinoma (RCC) is the most common renal malignancy accounting for 90% of the subtypes and approximately 80% of tumors are clear cell renal cell carcinoma (ccRCC).[2,3] In clinical therapy, surgical resection is just an effective treatment for localized tumor, but the disease still exhibits substantial mortality due to regional or distant metastasis 4 with a characteristic of high resistance toward conventional chemotherapy a radiotherapy.[5]. For advanced RCC patients, receptor of tyrosine kinase (RTK) inhibitors,[6] such as sunitinib, are regarded as the mainstay of therapeutic options, which has potent anti‐angiogenic effects and direct anti‐tumor activities owing to the inhibition of vascular endothelial growth factor receptor (VEGFR), platelet‐derived growth factor receptor, stem cell growth factor receptor, and FMS‐like tyrosine kinase 3 Despite their efficacy, many RCC patients end up with drug resistance and tumor progression after 6‐15 months of treatment except for those who are inherently refractory to sunitinib therapy.[7]. Single nucleotide polymorphisms (SNPs), which could correlate with RCC risk and survival, such as the association of G‐allele of rs231775 in the CTLA‐4 gene with an improved overall survival (OS) in sunitinib‐treated clear cell metastatic RCC patients,[18] have raised the attention of medical researchers At this time, according to several studies published to date, SNPs located in the lncRNA locus showed a highly significant association with the susceptibility of a variety of human tumors.[19-22]. We conducted a hospital‐based cohort study aiming to evaluate the association between lncARSR tagSNPs and RCC risk in a Chinese population
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