Xiong Yanlu, Lei Jie, Wen Miaomiao, Ma Yongfu, Zhao Jinbo, Tian Yahui, Wan Zitong, Li Xiaoyan, Zhu Jianfei, Wang Wenchen, Ji Xiaohong, Sun Ying, Yang Jie, Zhang Jiao, Xin Shaowei, Liu Yang, Jia Lintao, Han Yong, Jiang Tao
Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Innovation Center for Advanced Medicine, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Oncogenesis. 2025 Mar 5;14(1):5. doi: 10.1038/s41389-025-00546-5.
The prevention and precise treatment of early-stage lung adenocarcinoma (LUAD) characterized by small nodules (stage IA) remains a significant challenge for clinicians, which is due largely to the limited understanding of the oncogenic mechanisms spanning from preneoplasia to invasive adenocarcinoma. Our study highlights the pivotal role of cancer cells exhibiting high expression of centromere protein F (CENPF), driven by TP53 mutations, which become increasingly prevalent during the transition from preneoplasia to invasive LUAD. Biologically, cancer cells (CENPF+) exhibited robust proliferative and stem-like capabilities, thereby propelling the malignant progression of early-stage LUAD. Clinically, autoantibodies against CENPF in the serum and elevated cancer cells (CENPF+) in tissue correlated positively with the progression of early-stage LUAD, especially those in stage IA. Our findings suggest that cancer cells (CENPF+) play a central role in orchestrating the malignant evolution of LUAD and hold potential as a novel biomarker for early-stage detection and management of the disease.
以小结节为特征的早期肺腺癌（LUAD，I A期）的预防和精准治疗对临床医生来说仍然是一项重大挑战，这主要是由于对从癌前病变到浸润性腺癌的致癌机制了解有限。我们的研究强调了由TP53突变驱动的、表现为着丝粒蛋白F（CENPF）高表达的癌细胞的关键作用，这些癌细胞在从癌前病变向浸润性LUAD转变过程中变得越来越普遍。从生物学角度来看，癌细胞（CENPF+）表现出强大的增殖和干细胞样能力，从而推动早期LUAD的恶性进展。在临床上，血清中针对CENPF的自身抗体以及组织中升高的癌细胞（CENPF+）与早期LUAD的进展呈正相关，尤其是I A期的患者。我们的研究结果表明，癌细胞（CENPF+）在协调LUAD的恶性演变中起核心作用，并有望成为该疾病早期检测和管理的新型生物标志物。
