Resources

2019.06
Transcriptional characterization of microenvironment and their prediction role for the prognosis of Hepatocellular carcinoma after surgery

Author:Kehe Chen, Haiming Wei, Tianqi Liu, Zhenxiang Chen, Deng Pan, Jingning Huang, Ting Gao, Min Huang, Xiaoshuang Ren, Jiao Zhang, Beibei Mao, Ying Yang, Wenbo Han, Hongbo Zheng, Henghui Zhang


Background: Hepatocellular carcinoma (HCC) is one of the most common prevalent fatal cancers worldwide with poor prognosis due to high incidence of recurrence. For patients with HCC, surgical treatment is a potentially cutative therapy. However, the puzzle in the therapy was the rapid recurrence after surgery. The purpose of this study was to integrate the impact of different immune context present in HCC microenvironment on patients’ prognosis, provide the molecular prediction clue of HCC recurrence. 


Methods: RNA targeted sequencing was performed on 12 primary tumor specimens from HCC patients. Transcripts of 395 immune related genes expressed in FFPE tumor samples were analyzed. The lima package was used to analyze the different expressed genes (DEGs) between patients with different prognosis. The gene set variance analysis (GSVA) analysis was performed to explore gene sets enrichment related to the recurrence post-resection. 


Results: 15 DEGs were detected in tissue samples between the two groups (group A: patients who relapsed within one year after surgery; group B: patients who hadn't relapsed beyond two years after surgery). The Antigen processing pathway enrichment may associate with the favorable prognosis (p < 0.05). HLA-A gene expression in group A was lower than that in group B; The gene expression of IL23A, TP63, ALOX15B, BUB1, CXCR2, CCL20, CLEC4C, PTK7, MPO, IL1B, MMP9, GAGE2C, GAGE2A, GAGE2E, DMBT1, FOXM1 in group A was higher than that in group B. Additionally, the combination of 3 genes (TP63, IL23A and BUB1) can distinguish the patients recurrent within 1 year or beyond 2 years post-resection. The joint diagnostic equation is logit (Y = 1) = 0.073 +0.740 *(TP63) + 0.589 * (IL23A)+0.959(BUB1), (Optimal threshold: 0.667, specificity: 1, sensitivity: 0.833). 


Conclusions: Our results suggest that RNA-seq of immune related genes from FFPE sample can effectively profile the specific landscape of tumor immune microenvironment and predict the survival of HCC. 3 genes’ expression (TP63, IL23A and BUB1) might correlate with recurrence in HCC patients after surgery.