Liu Hongjin, Sun Xiaojiao, Dong Bingqi, Zhang Jixin, Zhang Junling, Gu Yanlun, Chen Lin, Pang Xiaocong, Ye Jingming, Wang Xin, Rong Zhuona
Department of Gastrointestinal Surgery, Peking University First Hospital, Beijing, China.
School of Pharmaceutical Sciences, Peking University, Beijing, China.
J Cell Mol Med. 2025 Apr;29(7):e70536. doi: 10.1111/jcmm.70536.
The intricacies of tumour microenvironment, particularly the extracellular matrix (ECM), underscore its pivotal function in modulating tumour progression and drug resistance. Among the key regulators of ECM remodelling and homeostasis, the lysyl oxidases (LOXs) emerge as promising therapeutic targets of tumour treatment. Despite their significance, a holistic evaluation of the LOX family's genomics and clinical implications across diverse cancer types remains elusive. Herein, this study aimed to investigate the correlation between LOX family expression and patient outcomes, drug responsiveness and tumour microenvironment (TME) characteristics in a cohort of 33 tumours based on The Cancer Genome Atlas (TCGA) database. Notably, patients exhibiting elevated LOX family expression suffer from worse prognosis and resistance to a spectrum of antitumor therapies, encompassing chemotherapy, endocrine therapy, targeted therapy and immunotherapy, in contrast to counterparts with subdued LOX family expression levels. Furthermore, enrichment analysis indicated that the LOX family fosters tumour progression and drug resistance. These findings were further validated by multiplex immunofluorescence staining in breast, gastric and rectal cancer, as well as breast cancer organoids. Altogether, this study unravels the intricate association between the LOX family and tumour progression, alongside multidrug resistance. We have gained further insights into the roles of LOX family genes in various tumour types, offering a novel avenue for future research into the relationship between LOX family genes and tumorigenesis.
肿瘤微环境的复杂性，尤其是细胞外基质（ECM），突显了其在调节肿瘤进展和耐药性方面的关键作用。在ECM重塑和稳态的关键调节因子中，赖氨酰氧化酶（LOXs）成为肿瘤治疗中颇具前景的治疗靶点。尽管它们具有重要意义，但对LOX家族在不同癌症类型中的基因组学和临床意义进行全面评估仍然难以实现。在此，本研究旨在基于癌症基因组图谱（TCGA）数据库，调查33种肿瘤队列中LOX家族表达与患者预后、药物反应性和肿瘤微环境（TME）特征之间的相关性。值得注意的是，与LOX家族表达水平较低的患者相比，LOX家族表达升高的患者预后较差，并且对一系列抗肿瘤治疗产生耐药性，这些治疗包括化疗、内分泌治疗、靶向治疗和免疫治疗。此外，富集分析表明，LOX家族促进肿瘤进展和耐药性。这些发现通过在乳腺癌、胃癌和直肠癌以及乳腺癌类器官中的多重免疫荧光染色得到进一步验证。总之，本研究揭示了LOX家族与肿瘤进展以及多药耐药之间的复杂关联。我们对LOX家族基因在各种肿瘤类型中的作用有了更深入的了解，为未来研究LOX家族基因与肿瘤发生之间的关系提供了一条新途径。
