Prognostic role of Ki-67 in colorectal carcinoma: Development and evaluation of machine learning prediction models

Ki-67 is a routine test item in clinical pathology departments. However, its prognostic value requires further investigation, especially in the context of research using machine learning (ML), which remains relatively underdeveloped.

To investigate the prognostic value of Ki-67 in cases of colorectal carcinoma (CRC) and explore the potential application of ML algorithms to predict the Ki-67 index.

Case data and pathological sections from two centers were systematically collected. To analyze the prognostic value of the Ki-67 index in CRC, multiple cutoff values were established. Meanwhile, by virtue of the histological features presented in the hematoxylin and eosin-stained CRC images, three mainstream ML algorithms, support vector machine (SVM), random forest (RF), and eXtreme gradient boosting (XGBoost) were employed to construct prediction models. Subsequently, the potential of these algorithms to classify and predict the Ki-67 index was explored.

Non-parametric tests revealed that Ki-67 ≥ 40% correlated with a high histological grade (P = 0.017), deficient mismatch repair protein status associated with ≥ 50%-90% cutoffs (all P ≤ 0.028), and ≥ 80% linked to lymph node metastasis (P = 0.006). Kaplan-Meier analysis showed that Ki-67 ≥ 50% predicted higher survival (log-rank P = 0.0299, hazard ratio = 2.142), with no differences for other cutoffs. COX regression identified the Ki-67 positive rate as a significant predictor (P = 0.027, hazard ratio = 2.583), while other variables had no association. In algorithmic model predictions, the SVM, RF, and XGBoost models achieved training area under the curve (AUC) values of 0.851, 0.948, and 0.872, respectively, with corresponding test set AUC values of 0.795, 0.755, and 0.750, respectively. During external validation, their AUC values for predicting Ki-67 status reached 0.757, 0.749, and 0.783, respectively.

In algorithmic model predictions, the SVM, RF, and XGBoost models achieved training AUC values of 0.851, 0.948, and 0.872, respectively, with corresponding test set AUC values of 0.795, 0.755, and 0.750, respectively. During external validation, their AUC values for predicting Ki-67 status reached 0.757, 0.749, and 0.783, respectively.