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Background Hepatocellular carcinoma (HCC) is one of the most common malignancies in China with poor prognosis. Recently, personalized neoantigen-based immunotherapy has been reported to induce robust anti-tumor immune responses to facilitate tumor rejection in several solid tumors. However, whether it possess therapeutic potential in HCC still remain unclear. Thus, a systemic understanding of neoantigen burden (TNB) in HCC microenvironment is in need. Methods HCC and matched peritumor tissue collected from 59 HCC patients were subjected to DNA and RNA sequencing for identifying tumor associated neoantigens. Then the association between neoantigens and clinical features, immune signatures, as well as clonal evolution patterns in HCC were evaluated. Results In enrolled HCC patients, a median of 106 somatic mutations and 15 neoantigens were identified in each patient. TNB was significantly correlated with tumor somatic mutation burden (R2 = 0.893, P = 3.0 × 10^-24). Furthermore, the clinicopathological analysis revealed that patients with higher TNB was characterized with older age (p = 0.006), decreased tumor size (p = 0.020) and lower recurrence rate (p = 0.019). Additionally, TNB was also significantly associated with relapse free survival (P = 0.033) and overall survival (P = 0.022) in HCC patients. Surprisingly, HCC tumor with high immune cell infiltration were more likely to have no tumor envelope (P = 0.027) and resulted in shorter overall survival time after surgery (P = 0.025); the patients with lower immune cell signatures related to antigen-processing have relatively higher TNB in HCC. Meanwhile, clonal evolution analysis revealed that the clonal mutations were more likely to be neoantigens (P = 9.2 × 10^-5) than subclonal mutations, suggesting higher immunogenicity for clonal mutations. And tumors with higher proportion of neoantigens in clonal mutations were more likely to involved in clonal evolution, which may due to the immunoediting of neoantigens (P = 0.002). Conclusions Our results demonstrated that neoantigens play an important role in tumor clonal evolution and immune response in HCC, which could provide insights for future HCC immunotherapy. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background The prognostic predictive value of breast cancer susceptibility gene 1 (BRCA1) for non-small-cell lung cancer (NSCLC) remains controversial. This study aimed to determine the prognostic effect of BRCA1 on NSCLC survival using meta-bioinformatic analysis. Methods Candidate articles were identified from PubMed, Embase, Cochrane Library, and Web of Science databases. Effect measures generated were the pooled hazard ratio (HR) and 95% confidence interval (CI). Cox regression model was performed in an independent dataset from TCGA to validate the accuracy of our meta-analysis. Results A total of 2462 patients from 15 studies of acceptable quality were included. No significant differences in overall survival (OS)/cancer-specific survival (CSS) (HR = 1.38, 95% CI: 0.95-2.00, P = 0.094) or progression-free survival (PFS)/disease-free survival (DFS)/relapse-free survival (RFS) (HR = 1.28, 95% CI: 0.82-2.00, P = 0.284) were observed between patients with high- and low-expression of BRCA1. However, patients with lung adenocarcinoma (LUAD) and increased BRCA1 expression had markedly poorer OS/CSS (HR = 1.78, 95% CI: 1.05-3.03, P = 0.032) than those with reduced BRCA1. Bioinformatics analysis also indicated that BRCA1 overexpression was independently correlated with decreased OS in LUAD. Moreover, patients with high BRCA1 were more likely to suffer from lymph node metastasis than those with low BRCA1. Conclusions Elevated BRCA1 expression may be a novel biomarker of poor OS for patients with LUAD. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Hepatocellular carcinoma (HCC) is the most common malignancy with high rates of recurrence and metastasis after radical resection. Vascular invasion, including portal vein tumor thrombus (PVTT) and microvascular invasion (MVI), and microsatellite lesions are two significant risk factors of postoperative recurrence and metastasis for HCC. Therefore, it is necessary to discover adjuvant therapies for patients with these risk factors. Anti-angiogenesis therapy combined with immunotherapy has demonstrated clinical benefits in multiple advanced solid neoplasms, including HCC. An exploratory phase Ib study (NCT02942329) proved that combined therapy of apatinib (250mg QD) and anti-PD-1 drug, SHR-1210 (200mg Q2W) was well tolerated and had preliminary efficacy in advanced HCC. Trial design This multicenter, randomized, controlled, phase II study will evaluate the safety and efficacy of adjuvant combined therapy of apatinib and anti-PD-1 drug, SHR-1210, compared with hepatic arterial infusion (HAI) chemotherapy, in patients with HCC at high risk of recurrence after radical resection. 200 patients, aged >18 years, Child-Pugh score 0 or 1, with histologically confirmed primary HCC, BCLC stage A or B diseases that are radical resected without other prior therapy for HCC and who are found to have microsatellite lesions, microvascular invasion or PVTT involved in second-order branch or above by preoperative imaging examination or postoperative pathological findings will be recruited and randomized (1:1) to receive apatinib (250mg QD) and SHR-1210 (200mg Q2W) for 6 months, or 2 times of standard HAI treatments (epirubicin 80-100mg or epirubicin 50mg+oxaliplatin 50mg). The primary endpoint is to compare recurrence-free survival and secondary endpoints include overall survival, safety, 1,2,3-year recurrence rate and Quality of Life score (QoL). Survival follow-up will continue for up to 3 years. The study is ongoing. Clinical trial identification NCT 03839550. Legal entity responsible for the study National Cancer Center/Cancer Hospital. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]