Luo Min-Yi, Han Zhe, Wang Jiaqi, Zhong Cheng, Chen Jiancong
Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
Department of Coloproctology, The Sixth Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
J Cancer. 2024 Jun 3;15(13):4113-4127. doi: 10.7150/jca.96800. eCollection 2024.
In the realm of cancer research, particularly hepatocellular carcinoma (HCC), TAR DNA-binding protein (TARDBP) has transitioned from being associated with neurodegenerative diseases to emerging as a significant molecule in oncology due to its aberrant expression in HCC and other malignancies. This shift underlines the versatility of TARDBP and its critical role in tumorigenesis. Our study illuminates TARDBP's universal upregulation across various cancers, indicating its involvement in fundamental oncogenic processes and potential impact on genomic instability. The relationship between TARDBP expression and tumor mutational burden (TMB) across several cancers highlights its influence on a key hallmark of cancer progression. Additionally, TARDBP's interaction with immune and inflammatory factors within the tumor microenvironment, including its association with immune-stimulatory factors and inverse relationship with immune inhibitors, suggests its role in modulating immune evasion. Clinically, TARDBP's aberrant expression correlates with adverse patient outcomes in HCC, making it a promising candidate for therapeutic targeting. The study concludes that TARDBP holds significant potential as a novel therapeutic target in HCC and possibly other malignancies, meriting further exploration to integrate TARDBP-targeted therapies into cancer treatment protocols, thereby advancing the field of precision medicine.
在癌症研究领域,尤其是肝细胞癌(HCC)研究中,TAR DNA结合蛋白(TARDBP)已从与神经退行性疾病相关联,转变为肿瘤学中的一个重要分子,因为它在HCC和其他恶性肿瘤中存在异常表达。这种转变突显了TARDBP的多功能性及其在肿瘤发生中的关键作用。我们的研究揭示了TARDBP在各种癌症中普遍上调,表明它参与了基本的致癌过程,并对基因组不稳定性具有潜在影响。TARDBP表达与多种癌症中的肿瘤突变负担(TMB)之间的关系突出了其对癌症进展的一个关键标志的影响。此外,TARDBP与肿瘤微环境中的免疫和炎症因子相互作用,包括其与免疫刺激因子的关联以及与免疫抑制剂的负相关关系,表明它在调节免疫逃逸中发挥作用。在临床上,TARDBP的异常表达与HCC患者的不良预后相关,使其成为一个有前景的治疗靶点。该研究得出结论,TARDBP作为HCC以及可能其他恶性肿瘤的新型治疗靶点具有巨大潜力,值得进一步探索将TARDBP靶向治疗纳入癌症治疗方案,从而推动精准医学领域的发展。