Tumor-associated collagen signatures and their clinical stage correlations in breast cancer as revealed by multiphoton microscopy

Breast cancer (BC) is a significant health concern for women, with its classification into multiple stages contingent upon the dimensions of the tumor, the extent of lymph node involvement, and the presence of distant metastasis. Despite the application of uniform treatment protocols to cases of similar staging, the outcomes are subject to variability due to the inherent heterogeneity of the disease, highlighting an urgent need for further investigation. The tumor microenvironment (TME) plays a pivotal role in tumor progression and metastasis, with collagen fibers emerging as a critical component of the TME that is implicated in these processes. However, the precise interplay between collagen fibers and tumor staging remains to be elucidated. Advancements in multiphoton microscopy (MPM), which capitalizes on nonlinear optical phenomena, have yielded impressive imaging capabilities, facilitating the real-time visualization of tumor histology and the quantification of metabolic activity within tumors. Recent studies have underscored the intricate relationship between collagen fibers and the dynamics of tumor evolution. <br/><br/> In this study, we utilized multiphoton microscopy to image three distinct tumor-associated collagen signatures (TACS) at the invasive front of the tumor. We then used MATLAB to extract the corresponding collagen morphological features and analyzed their correlation with clinical staging. Our results revealed significant changes in the morphological features of collagen fibers in TACS across different stages of BC at the tumor invasion front. Notably, the proportionate area and number of collagen fibers were found to be inversely correlated with the clinical staging risk group of the disease. Our findings offer new perspectives for the clinical staging of BC, providing valuable insights that may enhance the predictive accuracy of disease progression and prognostic outcomes.