Automated assessment of DNA ploidy, chromatin organization, and stroma fraction to predict prognosis and adjuvant therapy response in patients with stage II colorectal carcinoma

DNA ploidy, tumor stroma, and chromatin organization have important implications in tumorigenesis and patient outcome. Automated image cytometry tools were developed to quantitatively measure DNA ploidy (P), stroma fraction (S), and chromatin organization or Nucleotyping (N). This study aimed to discover their clinical value in different stages of colorectal cancer (CRC) in a Chinese patient population. A total of 496 CRC patients of stages I, II, and LMCRC (liver metastatic CRC) were enrolled in this study. Stage II CRC patients with diploidy, low-stroma, or chromatin homogenous status predicted significantly higher 5-year OS and DFS. We constructed a PSN-panel enabled the stage II patients to be further stratified into low-, middle-, high-risk groups, the 5-year OS (89.5% vs 67.9% vs 60.9%, P<0.001) and DFS (86.0% vs 62.3% vs 53.6%, P<0.001) were stratified significantly. In addition, when combined the PSN-panel with T stage or MSS status in stage II patients, the PSN-low risk patients showed significant longer 5-year OS and DFS than the PSN-high risk patients in T3 (OS: 86.3% vs 65.3%, P=0.015; DFS: 83.5 vs 59.8%, P=0.013) or MSS (OS: 86.4% vs 63.9%, P=0.005; DFS: 85.5 vs 57.8%, P=0.003) patients. Finally, in the group of stage II patients with at least one high-risk factor (non-diploidy, high-stroma, chromatin heterogenous), patients who received adjuvant therapy showed significantly longer OS (72.1% vs 48.3%, P=0.007) and DFS (64.5% vs 43.9%, P=0.015) than those who did not receive adjuvant therapy. In contrast, P, S, N couldn't predict the prognosis of stage I and LMCRC patients. Overall, our data demonstrate that the PSN panel is an accurate prognostic tool that can guide treatment decisions for Chinese stage II CRC patients.