Gitau John, Kinyori Godfrey, Sayed Shahin, Saleem Mohammad, Makokha Francis W, Kirabo Annet
Directorate of Research and Innovation, Mount Kenya University, Thika, Kenya.
Aga Khan University hospital, Nairobi, Kenya.
bioRxiv. 2024 Jun 9:2024.06.07.597892. doi: 10.1101/2024.06.07.597892.
Breast cancer is the most common malignant tumor in women worldwide, and disproportionately affects Sub-Saharan Africa compared to high income countries. The global disease burden is growing, with Sub-Saharan Africa reporting majority of the cases. In Kenya, breast cancer is the most commonly diagnosed cancer, with an annual incidence of 7,243 new cases in 2022, representing 25.5% of all reported cancers in women. Evidence suggests that women receiving breast cancer treatment are at a greater risk of developing hypertension than women without breast cancer. Hypertension prevalence has been on the rise in SSA, with poor detection, treatment and control. The JAK-STAT signaling is activated in hormone receptor-positive breast tumors, leading to inflammation, cell proliferation, and treatment resistance in cancer cells. We sought to understand the association between the expression of JAK-STAT Pathway genes and hypertension among Kenyan women diagnosed with breast cancer.
Breast tumor and non-tumor tissues were acquired from patients with a pathologic diagnosis of invasive breast carcinoma. RNA was extracted from fresh frozen tumor and adjacent normal tissue samples of 23 participants who had at least 50% tumor after pathological examination, as well as their corresponding adjacent normal samples. Differentially expressed JAK-STAT genes between tumor and normal breast tissues were assessed using the DESEq2 R package. Pearson correlation was used to assess the correlation between differentially expressed JAK-STAT genes and participants' blood pressure, heart rate, and body mass index (BMI).
11,868 genes were differentially expressed between breast tumor and non-tumor tissues. Eight JAK-STAT genes were significantly dysregulated (Log2FC ≥ 1.0 and an Padj ≤ 0.05), with two genes (CISH and SCNN1A) being upregulated. Six genes (TGFBR2, STAT5A, STAT5B, TGFRB3, SMAD9, and SOCS2) were downregulated. We identified STAT5A and SOCS2 genes to be significantly correlated with elevated systolic pressure and heart rate, respectively.
Our study provides insights underlying the molecular mechanisms of hypertension among Kenyan women diagnosed with breast cancer. Understanding these mechanisms may help develop targeted treatments that may improve health outcomes of Kenyan women diagnosed with breast cancer. Longitudinal studies with larger cohorts will be needed to validate our results.
乳腺癌是全球女性中最常见的恶性肿瘤，与高收入国家相比，撒哈拉以南非洲地区受其影响的比例过高。全球疾病负担正在增加，撒哈拉以南非洲地区报告的病例占多数。在肯尼亚，乳腺癌是最常被诊断出的癌症，2022年的年发病率为7243例新病例，占所有报告的女性癌症的25.5%。有证据表明，接受乳腺癌治疗的女性患高血压的风险比未患乳腺癌的女性更高。撒哈拉以南非洲地区的高血压患病率一直在上升，其检测、治疗和控制情况不佳。JAK-STAT信号通路在激素受体阳性的乳腺肿瘤中被激活，导致癌细胞发生炎症、细胞增殖和治疗抵抗。我们试图了解肯尼亚乳腺癌女性患者中JAK-STAT通路基因表达与高血压之间的关联。
从经病理诊断为浸润性乳腺癌的患者中获取乳腺肿瘤和非肿瘤组织。从23名参与者的新鲜冷冻肿瘤及相邻正常组织样本中提取RNA，这些参与者在病理检查后肿瘤组织至少占50%，同时获取其相应的相邻正常样本。使用DESEq2 R软件包评估肿瘤和正常乳腺组织之间差异表达的JAK-STAT基因。采用Pearson相关性分析评估差异表达的JAK-STAT基因与参与者的血压、心率和体重指数（BMI）之间的相关性。
乳腺肿瘤和非肿瘤组织之间有11868个基因差异表达。8个JAK-STAT基因显著失调（Log2FC≥1.0且Padj≤0.05），其中2个基因（CISH和SCNN1A）上调。6个基因（TGFBR2、STAT5A、STAT5B、TGFRB3、SMAD9和SOCS2）下调。我们发现STAT5A和SOCS2基因分别与收缩压升高和心率显著相关。
我们的研究揭示了肯尼亚乳腺癌女性患者高血压的分子机制。了解这些机制可能有助于开发针对性的治疗方法，从而改善肯尼亚乳腺癌女性患者的健康结局。需要进行更大样本量的纵向研究来验证我们的结果。
