基于生物标志物的卵巢癌（OC）及双酚 A（BPA）暴露相关 OC 的 SNP 结构和功能预测的计算机模拟研究

In Silico Study to Predict the Structural and Functional Consequences of SNPs on Biomarkers of Ovarian Cancer (OC) and BPA Exposure-Associated OC.

机构信息

Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK.

Mount Vernon Cancer Centre, Northwood HA6 2RN, UK.

出版信息

Int J Mol Sci. 2022 Feb 2;23(3):1725. doi: 10.3390/ijms23031725.

BACKGROUND

Recently, we have shown that seven genes, namely , , , , , and have prognostic power for the overall survival in ovarian cancer (OC).

METHODS

We present an analysis on the association of these genes with any phenotypes and mutations indicative of involvement in female cancers and predict the structural and functional consequences of those SNPS using in silico tools.

RESULTS

These seven genes present with 976 SNPs/mutations that are associated with human cancers, out of which 284 related to female cancers. We have then analysed the mutation impact on amino acid polarity, charge and water affinity, leading to the identification of 30 mutations in gynaecological cancers where amino acid (aa) changes lead to opposite polarity, charges and water affinity. Out of these 30 mutations identified, only a missense mutation (i.e., R831C/R804C in uterine corpus endometrial carcinomas, UCEC) was suggestive of structural damage on the protein.

CONCLUSIONS

We demonstrate that the R831C/R804C mutation is deleterious and the predicted ΔΔG values suggest that the mutation reduces the stability of the protein. Future in vitro studies should provide further insight into the role of this transporter protein in UCEC.

背景

最近，我们已经证实，有七个基因，即、、、、、和，对卵巢癌（OC）的总生存具有预后能力。

方法

我们对这些基因与任何表型和突变的关联进行了分析，这些突变表明它们参与了女性癌症，并使用计算机工具预测了这些 SNP 的结构和功能后果。

结果

这七个基因存在 976 个与人类癌症相关的 SNP/突变，其中 284 个与女性癌症相关。然后，我们分析了突变对氨基酸极性、电荷和水亲和力的影响，从而确定了 30 个在妇科癌症中导致氨基酸（aa）变化导致相反极性、电荷和水亲和力的突变。在这 30 个鉴定的突变中，只有一个错义突变（即子宫体子宫内膜癌 UCEC 中的 R831C/R804C）提示蛋白结构损伤。