Fig. 1

The flowchart of this study. Large-scale TACSs were visually examined on SHG images by three independent reviewers. A total of 142 TACS corresponding microscopic features (TCMFs) were extracted from SHG images. Ridge regression and LASSO regression were used to calculate the TACS- and TCFM-score, and then the two scores were combined for a series of prognostic analysis. TACS1, curved collagen fibers wrap around the emergent tumor foci; TACS2, collagen fibers are stretched due to tumor growth and align more parallel to tumor boundary; TACS3, collagen fibers align perpendicular to the tumor boundary in a radiation pattern to facilitate tumor cell migration; TACS4, reticular distribution of collagen fibers adjacent to expanding tumor that leads to a clear tumor boundary; TACS5, directionally distributed collagen fibers that enable unidirectional tumor cell migration without a clear tumor boundary; TACS6, chaotically aligned collagen fibers that enable multidirectional tumor cell migration without a clear tumor boundary; TACS7, densely distributed collagen fibers at the tumor invasion front largely free of tumor cells; TACS8, sparsely distributed collagen fibers at the tumor invasion front largely free of tumor cells