Zafar Sameen, Badshah Yasmin, Shabbir Maria, Mussarat Uzma, Latif Asma, Trembley Janeen H, Afsar Tayyaba, Husain Fohad Mabood, Razak Suhail
Department of Bioscience, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, 44000, Pakistan.
Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
Breast Cancer Res. 2025 Jul 28;27(1):139. doi: 10.1186/s13058-025-02090-x.
Missense single-nucleotide polymorphisms (SNPs) in various genetic pathways can lead to the development of breast cancer. Protein kinase C delta (PRKCD) is involved in various important cellular pathways, and its altered expression has been identified in different cancers. Genetic alteration in this gene can be involved in cancer onset and progression. To date, there are no studies performed to elucidate the role of PRKCD missense variants in the development of breast cancer. Therefore, this study aims to identify the association of pathogenic missense SNPs in PRKCD with breast cancer.
The missense variants of PRKCD were retrieved from the Ensembl and dbSNP databases. Missense variants were analysed through various computational tools, and four variants of PRKCD rs1703806197 (T/C), rs782555227 (G/A), rs1703449438 (T/C), and rs1575535582 (T/G) were selected from the data. The genotype analysis for these variants was performed for 360 breast cancer patients and 363 healthy controls. Statistical association of variants with breast cancer clinical features was determined through chi-square/Fisher's exact test with a significant P value ≤ 0.05 using GraphPad Prism 8.0 software.
Genotype analysis of PRKCD variants showed that missense SNPs rs782555227 (G/A), rs1703449438 (T/C), and rs1575535582 (T/G) were associated with breast cancer (P value < 0.05). Furthermore, genotypes in these SNPs were also found to be associated with various clinical features of breast cancer patients. Genotypes AG, TC, and TT in variants rs782555227, rs1703449438, and rs1575535582, respectively, were associated with breast cancer metastasis. While genotype AG of variant rs782555227 was also found to be associated with menopausal status and hereditary breast cancer. Moreover, genotype TT in variant rs1575535582 was associated with BRCA1 positive status among the breast cancer patients.
The present study identified for the first time the association of specific PRKCD missense variants with breast cancer. These variants could be developed into possible genetic markers for the diagnosis of breast cancer at an early stage; however, further validation studies with a multiethnic large cohort size are required. Furthermore, functional studies of these variants will also aid in attaining insight into the molecular mechanisms through which these missense variants are involved in breast cancer.
各种遗传途径中的错义单核苷酸多态性（SNP）可导致乳腺癌的发生。蛋白激酶Cδ（PRKCD）参与多种重要的细胞途径，并且在不同癌症中已发现其表达改变。该基因的遗传改变可能与癌症的发生和进展有关。迄今为止，尚未有研究阐明PRKCD错义变体在乳腺癌发生中的作用。因此，本研究旨在确定PRKCD中致病性错义SNP与乳腺癌的关联。
从Ensembl和dbSNP数据库中检索PRKCD的错义变体。通过各种计算工具对错义变体进行分析，并从数据中选择PRKCD的四个变体rs1703806197（T/C）、rs782555227（G/A）、rs1703449438（T/C）和rs1575535582（T/G）。对360例乳腺癌患者和363例健康对照进行这些变体的基因型分析。使用GraphPad Prism 8.0软件，通过卡方检验/费舍尔精确检验确定变体与乳腺癌临床特征的统计学关联，显著性P值≤0.05。
PRKCD变体的基因型分析表明，错义SNP rs782555227（G/A）、rs1703449438（T/C）和rs1575535582（T/G）与乳腺癌相关（P值<0.05）。此外，还发现这些SNP中的基因型与乳腺癌患者的各种临床特征相关。变体rs782555227、rs1703449438和rs1575535582中的基因型AG、TC和TT分别与乳腺癌转移相关。同时，变体rs782555227的基因型AG还与绝经状态和遗传性乳腺癌相关。此外，变体rs1575535582中的基因型TT与乳腺癌患者中的BRCA1阳性状态相关。
本研究首次确定了特定PRKCD错义变体与乳腺癌的关联。这些变体可开发成为早期诊断乳腺癌的潜在遗传标志物；然而，需要进行多民族大样本队列的进一步验证研究。此外，对这些变体的功能研究也将有助于深入了解这些错义变体参与乳腺癌的分子机制。
