Source: The First Affiliated Hospital
Written by: The First Affiliated Hospital
Edited by: Wang Dongmei

Recently, Prof. Ming Kuang and his colleagues from the First Affiliated Hospital of Sun Yat-sen University (FAH-SYSU) revealed the genetic revolution and immune infiltration profiles of multifocal hepatocellular carcinoma (HCC). The results were published online in the official journal of the European Society of Medical Oncology--- Annals of Oncology (IF: 13.930), with Prof. Ming Kuang as the corresponding author, Dr. Lixia Xu as the first author, Prof. Jun Yu from the Institute of Precision Medicine as a co-author and the FAH-SYSU as the corresponding institute.

Prof. Kuang’s team performed whole exome sequencing (WES) with high resolution in 34 tumors from 6 multifocal HCC patients. They demonstrated that most multifocal HCC originated from intrahepatic metastasis with some common mutations among different nodules. Further evolutionary trajectory analysis revealed that each nodule presented a relatively independent clonal evolution pattern, with only 20% of druggable alterations mapped to the trunks of phylogenetic tree, which were shared by all nodules. Of note, sorafenib-targeted alterations were identified in the trunk in only one out of six patients, suggesting a theoretical response of all nodules to sorafenib treatment in this patient. These data deciphered the maldistribution of druggable targets caused by clonal evolution and provided rationale for the targeted treatment to prevent post-surgery recurrence of multifocal HCC.

Moreover, through RNA-seq, they firstly reported the immune microenvironment heterogeneity of multifocal HCC and found that the composition of immune cells varied substantially across different tumors even within one patient. By unsupervised hierarchical clustering analysis upon differentially expressed immune-related genes, tumors could be divided into high-immune and low-immune clusters. In high-immune tumors, high expression of suppressive immune markers including PD1 were also observed, indicating that patients with high-immune HCCs might benefit from PD1/PDL1 inhibitors and shedding light on the selection of targeted patients for immunotherapy.

Article link: https://academic.oup.com/annonc/advance-article-abstract/doi/10.1093/annonc/mdz103/5420549?redirectedFrom=fulltext