AUTHOR=Qu Wei-Feng , Tian Meng-Xin , Qiu Jing-Tao , Guo Yu-Cheng , Tao Chen-Yang , Liu Wei-Ren , Tang Zheng , Qian Kun , Wang Zhi-Xun , Li Xiao-Yu , Hu Wei-An , Zhou Jian , Fan Jia , Zou Hao , Hou Ying-Yong , Shi Ying-Hong 

TITLE=Exploring pathological signatures for predicting the recurrence of early-stage hepatocellular carcinoma based on deep learning

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.968202

DOI=10.3389/fonc.2022.968202

ISSN=2234-943X

ABSTRACT=Background: Postoperative recurrence impedes the curability of early-stage hepatocellular carcinoma (E-HCC). We aimed to establish a novel recurrence-related pathological prognosticator with artificial intelligence, and investigate the relationship between pathological features and the local immunological microenvironment.
Methods: A total of 576 whole-slide images (WSIs) were collected from 547 patients with E-HCC in the Zhongshan cohort, which was randomly divided into a training cohort and a validation cohort. The external validation cohort comprised 147 Tumor Node Metastasis (TNM) stage I patients from The Cancer Genome Atlas (TCGA) database. Six types of HCC tissues were identified by a weakly supervised convolutional neural network. A recurrence-related histological score (HS) was constructed and validated. The correlation between immune microenvironment and HS was evaluated through extensive immunohistochemical data.
Results: The overall classification accuracy of HCC tissues was 94.17%. The C-indexes of HS in the training, validation and TCGA cohorts were 0.804, 0.739 and 0.708, respectively. Multivariate analysis showed that the HS (HR= 4.05, 95% CI: 3.40-4.84) was an independent predictor for recurrence-free survival. Patients in HS high-risk group had elevated preoperative alpha-fetoprotein levels, poorer tumor differentiation and a higher proportion of microvascular invasion. The immunohistochemistry data linked the HS to local immune cell infiltration. HS was positively correlated with the expression level of peritumoral CD14+ cells (p= 0.013), and negatively with the intratumoral CD8+ cells (p< 0.001).
Conclusions: The study established a novel histological score that predicted short-term and long-term recurrence for E-HCCs using deep learning, which could facilitate clinical decision making in recurrence prediction and management.