KRAS和NOXA基因作为卵巢癌潜在生物标志物的表达谱分析。
Expression profiling of KRAS and NOXA genes as prospective biomarkers in ovarian carcinoma.
作者信息
Abdelnaeem Kholoud, Dawood Reham Mohammed, Fotouh Basma E, Ismail Abeer, Abdalla Mohga S, Ramadan Shimaa S
机构信息
Molecular Biotechnology Sector, Chemistry Department, Faculty of Science, Helwan University, Cairo, Egypt.
Microbial Biotechnology Department, Biotechnology Research Institute, National Research Centre, EL Bohouth St. Dokki, P.O. 12622, Giza, Egypt.
出版信息
Sci Rep. 2025 Sep 5;15(1):32370. doi: 10.1038/s41598-025-17650-6.
BACKGROUND
Ovarian cancer (OC) is a leading cause of cancer deaths in women. Comprehensive molecular studies are required to understand OC pathogenesis. KRAS and NOXA genes are involved in tumorigenesis and disease progression. KRAS promotes tumor growth, while NOXA triggers the apoptotic signaling pathway.
METHODS
Fifty-six ovarian cancer patients and twenty healthy controls were enrolled in the study. Gene expression profiling was performed utilizing the qRT-PCR assay. Then, the proteomic levels of KRAS and NOXA genes were assessed by the ELISA technique.
RESULTS
The results showed that KRAS gene expression was significantly increased in OC patients compared to controls (p < 0.0001). Additionally, KRAS overexpression was correlated significantly with more aggressive characteristics, including advanced stage, positive lymph invasion, and metastatic status (p = 0.04, 0.05, and 0.02, respectively). In contrast, NOXA expression was downregulated in OC patients compared to controls (p = 0.001), and this reduction was more pronounced in patients with more aggressive characteristics (p = 0.001, 0.01, 0.0008, 0.02, respectively). At the transcriptomic level, KRAS concentration was higher among the patient group (p = 0.03) and correlated with aggressive tumor features (p = < 0.0001, 0.001, and 0.03, respectively). Interestingly, no significant changes were detected in NOXA protein levels concerning ovarian cancer development and progression. These findings were further confirmed by receiver operating characteristic (ROC) curve analysis, validating the genetic and transcriptomic results.
CONCLUSION
The differential expression of KRAS and NOXA genes holds promise as potential biomarkers for ovarian cancer development and progression. Specifically, KRAS transcriptomic levels serve as a reliable discriminator of ovarian cancer progression. In contrast, NOXA protein expression warrants further investigation to elucidate its role in the progression and pathophysiology of ovarian cancer.
背景
卵巢癌（OC）是女性癌症死亡的主要原因。需要进行全面的分子研究以了解OC的发病机制。KRAS和NOXA基因参与肿瘤发生和疾病进展。KRAS促进肿瘤生长，而NOXA触发凋亡信号通路。
方法
56例卵巢癌患者和20名健康对照者纳入本研究。利用qRT-PCR检测进行基因表达谱分析。然后，通过ELISA技术评估KRAS和NOXA基因的蛋白质组水平。
结果
结果显示，与对照组相比，OC患者中KRAS基因表达显著增加（p < 0.0001）。此外，KRAS过表达与更具侵袭性的特征显著相关，包括晚期、阳性淋巴结浸润和转移状态（分别为p = 0.04、0.05和0.02）。相反，与对照组相比，OC患者中NOXA表达下调（p = 0.001），并且在具有更具侵袭性特征的患者中这种降低更为明显（分别为p = 0.001、0.01、0.0008、0.02）。在转录组水平上，患者组中KRAS浓度较高（p = 0.03），并且与侵袭性肿瘤特征相关（分别为p < 0.0001、0.001和0.03）。有趣的是，关于卵巢癌的发生和进展，未检测到NOXA蛋白水平有显著变化。这些发现通过受试者工作特征（ROC）曲线分析得到进一步证实，验证了基因和转录组结果。
结论
KRAS和NOXA基因的差异表达有望成为卵巢癌发生和进展的潜在生物标志物。具体而言，KRAS转录组水平可作为卵巢癌进展的可靠判别指标。相反，NOXA蛋白表达值得进一步研究以阐明其在卵巢癌进展和病理生理学中的作用。
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