Collagen Signature as a Novel Biomarker to Predict Axillary Lymph Node Metastasis in Breast Cancer Using Multiphoton Microscopy

Abstract

Background: Accurate identification of axillary lymph node (ALN) status is crucial for tumour staging procedure and decision making. The aim of this study is to evaluate the diagnostic performance of clinical parameters combined with collagen signatures (tumour-associated collagen signatures (TACS) and the TACS corresponding microscopic features (TCMF)) in predicting the probability of ALN metastasis in patients with breast cancer. Methods: This retrospective study of 898 participants from two institutions was conducted. Collagen signatures (TACS and TCMF) were generated by multiphoton microscopy (MPM) imaging and feature extraction. Logistic analysis was used to determine the association of clinical parameters, TACS and TCMF with ALN metastasis. Findings: TACS and TCMF were significant predictors of ALN status. A nomogram based on independent clinical parameters combined with TACS and TCMF was developed to predict the probability of ALN metastasis with an area under the receiver operating curve (AUC) of 0.783 in the training cohort, 0.747 in the internal validation cohort, and 0.746 in the external validation cohort. Interpretation: These findings suggest that TACS and TCMF in the breast tumour microenvironment are both novel and independent biomarkers for the estimation of ALN metastasis. The nomogram yields good diagnostic performance in predicting ALN status. Funding: Fujian Major Scientific and Technological Special Project for “Social Development” (No. 2020YZ016002), Special Funds of the Central Government Guiding Local Science and Technology Development (No. 2020L3008), Natural Science Foundation of China (Nos. 81901787, 81700576), Natural Science Foundation of Fujian Province (Nos. 2019J01269, 2020J011008, 2020J01154). Declaration of Interest: The authors declare no competing interests. Ethical Approval: This retrospective study used anonymous data which was approved by the Institutional Review Board of Fujian Medical University Union Hospital (Fuzhou, China) and Harbin Medical University Cancer Hospital (Harbin, China).