Molecular Biology Laboratory, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, India.
Department of Oral and Maxillofacial Surgery, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, India.
J Stomatol Oral Maxillofac Surg. 2024 Oct;125(5S2):101971. doi: 10.1016/j.jormas.2024.101971. Epub 2024 Jul 18.
Head and neck squamous cell carcinoma (HNSCC) present a significant challenge in the medical field due to treatment resistance, which often hinders successful outcomes. The dysregulation of the LRP1B gene is linked to various cancers, but its specific role in HNSCC is poorly understood.
This study investigated the link between pathogenic loss-of-function mutations in the LRP1B gene and survival outcomes in HNSCC patients. The Cancer Genome Atlas HNSCC cohort, comprised of 520 tumor and 44 normal tissues, was analyzed using cBioportal, and UALCAN tools. Expression patterns, survival outcomes, and clinical correlations of LRP1B were evaluated. In-depth analyses involved validation of mRNA expression using RT-qPCR and functional exploration using various in-silico tools.
Analysis of data from The Cancer Genome Atlas (TCGA) and cBioPortal revealed a high frequency (25 %) of LRP1B mutations in HNSCC patients. Notably, splice mutation, truncating mutation, and deep deletion, considered potential drivers, are commonly associated with LRP1B mutations. Patients with LRP1B mutations also exhibit poorer overall survival rates compared to those without these mutations. Furthermore, LRP1B mRNA expression is significantly reduced in HNSCC tissues compared to normal tissues and is correlated with advanced tumor stage, higher tumor grade, and nodal metastasis.
These findings indicate that LRP1B may function as both a prognostic biomarker and a therapeutic target in HNSCC patients.
头颈部鳞状细胞癌（HNSCC）是医学领域的一个重大挑战，因为治疗耐药性常常阻碍了治疗效果。LRP1B 基因的失调与各种癌症有关，但它在 HNSCC 中的具体作用尚不清楚。
本研究探讨了 LRP1B 基因的致病性失活突变与 HNSCC 患者生存结局之间的联系。使用 cBioportal 和 UALCAN 工具分析了包含 520 个肿瘤和 44 个正常组织的癌症基因组图谱 HNSCC 队列。评估了 LRP1B 的表达模式、生存结局和临床相关性。通过 RT-qPCR 验证了 mRNA 表达的深入分析，并使用各种计算机模拟工具进行了功能探索。
对癌症基因组图谱（TCGA）和 cBioPortal 数据的分析显示，HNSCC 患者中 LRP1B 突变的频率较高（25%）。值得注意的是，剪接突变、截断突变和深缺失被认为是潜在的驱动突变，与 LRP1B 突变密切相关。与没有这些突变的患者相比，LRP1B 突变患者的总生存率也较低。此外，与正常组织相比，HNSCC 组织中 LRP1B mRNA 表达显著降低，并且与肿瘤分期较晚、肿瘤分级较高和淋巴结转移相关。
这些发现表明，LRP1B 可能在 HNSCC 患者中既作为预后生物标志物，又作为治疗靶点发挥作用。
