408P Increased EGFR and MET Expression and Corresponding Tumor Microenvironment (TME) Change in Hepatocellular Carcinoma (HCC) Tissues after Sorafenib (sora) Treatment

Despite the recent progress of immune therapies and multi-kinase inhibitors such as Sora, the 5-year survival rate for late-stage HCC remains dismal. The high prevalence and distinct etiology of HCC in Asia Pacific represent high unmet medical needs. Considering EGFR and MET are frequently over-expressed in HCC and often correlate with poor prognosis, we evaluated the impact of Sora on EGFR and MET expression (expr) and TME in treating late-stage HCC. We also evaluated the association of EGFR and MET expr, etiology and TME. Total 51 HCC patients (pts) with tumor tissues before 1st-line Sora treatment (Tx) and 43 paired post- Sora samples obtained for immunohistochemistry (IHC) and RNA sequencing (RNAseq) analysis. The formalin-fixed, paraffin-embedded (FFPE) tissues were analyzed for EGFR and MET expr by IHC using EGFR D38B1 and MET SP44 antibodies. Staining intensity was scored on a scale of 0, 1+, 2+ and 3+. RNAseq was successfully conducted in 60 FFPE tissues (33 pre- and 27 post- Sora samples) by TruSeq RNA Access library preparation. R package immunedeconv was used for TME estimation. The median duration of Sora Tx was 126 days for study group. Overall, H score of EGFR and MET expr was higher in post- Sora than in pre- Sora samples (Median value: EGFR 100 vs 55; MET 110 vs 85). On a pt level, increased EGFR and MET expr in IHC>=2+ was observed respectively in 53% and 41% of HCC pts post Sora Tx. Interestingly, H score of MET expr in HBV+ group was higher than that in HBV- group (p = 0.003). MET gene expr also showed similar trend (p = 0.002) but not for EGFR. Different cut-off for EGFR and MET IHC expr showed similar results as above. Furthermore, a trend of positive correlation was observed between robust MET IHC staining and myeloid dendritic cell activated score (RNAseq) post Sora Tx (n = 26). This is the first time to report EGFR and MET IHC expr from pre- and post- Sora HCC samples using different cut off scores. EGFR and MET expr was higher in post- Sora than in pre- Sora samples. MET expr in HBV+ group was higher than that in HBV- group. The mechanisms and clinical significance of these observations warrant further investigation.