Systematic Characterisation and Analysis of Lysyl Oxidase Family Members as Drivers of Tumour Progression and Multiple Drug Resistance

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.