Prediction of lymphovascular space invasion using a combination of tenascin-C, cox-2, and PET/CT radiomics in patients with early-stage cervical squamous cell carcinoma

BACKGROUND Lymphovascular space invasion is an independent prognostic factor in early-stage cervical cancer. However, there is a lack of non-invasive methods to detect lymphovascular space invasion. Some researchers found that Tenascin-C and Cyclooxygenase-2 was correlated with lymphovascular space invasion. Radiomics has been studied as an emerging tool for distinguishing tumor pathology stage, evaluating treatment response, and predicting prognosis. This study aimed to establish a machine learning model that combines radiomics based on PET imaging with tenascin-C (TNC) and cyclooxygenase-2 (COX-2) for predicting lymphovascular space invasion (LVSI) in patients with early-stage cervical cancer. METHODS One hundred and twelve patients with early-stage cervical squamous cell carcinoma who underwent PET/CT examination were retrospectively analyzed. Four hundred one radiomics features based on PET/CT images were extracted and integrated into radiomics score (Rad-score). Immunohistochemical analysis was performed to evaluate TNC and COX-2 expression. Mann-Whitney U test was used to distinguish differences in the Rad-score, TNC, and COX-2 between LVSI and non-LVSI groups. The correlations of characteristics were tested by Spearman analysis. Machine learning models including radiomics model, protein model and combined model were established by logistic regression algorithm and evaluated by ROC curve. Pairwise comparisons of ROC curves were tested by DeLong test. RESULTS The Rad-score of patients with LVSI was significantly higher than those without. A significant correlation was shown between LVSI and Rad-score (r = 0.631, p < 0.001). TNC was correlated to both the Rad-score (r = 0.244, p = 0.024) and COX-2 (r = 0.227, p = 0.036). The radiomics model had the best predictive performance among all models in training and external dataset (AUCs: 0.914, 0.806, respectively, p < 0.001). However, in testing dataset, the combined model had better efficiency for predicting LVSI than other models (AUCs: 0.801 vs. 0.756 and 0.801 vs. 0.631, respectively). CONCLUSION The machine learning model of the combination of PET radiomics with COX-2 and TNC provides a new tool for detecting LVSI in patients with early-stage cervical cancer. In the future, multicentric studies on larger sample of patients will be used to test the model. TRIAL REGISTRATION This is a retrospective study and there is no experimental intervention on human participants. The Ethics Committee has confirmed that retrospectively registered is not required.