AI Driven C02-TFunctionalProg

Research method used for: Recurrence risk of MSS stage II colorectal cancer.

Interpretation of results: The AI method outputs 2 scores in the range of [-1 – 1], any score > 0 predicts that a stage II MSS colorectal tumor sample is likely high recurrence risk subtype.

C02-TFunctionalProg test recurrence risk of MSS stage II colorectal cancer and selects effective personalized adjuvant drugs for stage II colorectal cancer patients who have a high risk of recurrence. C02-TFunctionalProg was validated on formalin-fixed, paraffin-embedded(FFPE) samples of 222 high quality stage II microsatellite stable(MSS) colorectal cancer patients(median follow-up=41 months, main endpoint recurrence-free survival. Stage II colorectal cancer patients who had no recurrence but received adjuvant/neoadjuvant chemotherapy/radiotherapy were excluded from this cohort). C02-TFunctionalProg low-risk group of stage II colorectal cancer patients have 3-years recurrence free survival >92% and may consider forgoing adjuvant therapy. C02-TFunctionalProg high-risk group of stage II colorectal cancer patients have 3-years recurrence free survival <60% (Figure 1,2), and C02-TFunctionalProg proposes personalized rational adjuvant drugs for these high-risk patients.

Different from ctDNA-based prognostic biomarkers that are used as indicators of minimal residual disease, C02-TFunctionalProg aims to dissect the underlying biology of recurrence of stage II colorectal cancer and subgroups of epithelial mesenchymal transition. Therefore, C02-TFunctionalProg provides several differentiated features and a differentiated modality for the management of stage II CRC:

       (1) The observed sensitivity of C02-TFunctionalProg of predicting the recurrence of stage II colorectal cancer is between 70% (Figure 1A.Independent validation) – 85% (Figure 1B.Leave-One-Out cross validation), and this sensitivity is higher than the observed sensitivity of postoperative ctDNA-based prognostic biomarkers for predicting recurrence of stage II colorectal cancer in clinical trials^# (Tie J, et al. N Engl J Med. 2022; Reinert T, et al. JAMA Oncol. 2019; Chen G, et al. J Hematol OncolJ Hematol Oncol. 2021)

       (2) C02-TFunctionalProg utilizes standard 5 µm/10 µm formalin-fixed, paraffin-embedded(FFPE) slides that can be stored at room temperature, thus the operation cost is significantly lower.

       (3) C02-TFunctionalProg is a prognostic assay with integrated functions that indicate adjuvant chemotherapy response (Figure 3).