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| 1 | Profiling of hepatocellular carcinoma neoantigens reveals immune microenvironment and clonal evolution related patterns显示文摘Objective: Neoantigens derived from tumor-specific genomic alterations have demonstrated great potential for immunotherapeutic interventions in cancers. However, the comprehensive profile of hepatocellular carcinoma(HCC) neoantigens and their complex interplay with immune microenvironment and tumor evolution have not been fully addressed.Methods: Here we integrated whole exome sequencing data, transcriptome sequencing data and clinical information of 72 primary HCC patients to characterize the HCC neoantigen profile, and systematically explored its interactions with tumor clonal evolution, driver mutations and immune microenvironments.Results: We observed that higher somatic mutation/neoantigen load was associated with better clinical outcomes and HCC patients could be further divided into two subgroups with distinct prognosis based on their neoantigen expression patterns. HCC subgroup with neoantigen expression probability high(NEP-H) showed more aggressive pathologic features including increased incidence of tumor thrombus(P=0.038), higher recurrence rate(P=0.029),more inclined to lack tumor capsule(P=0.026) and with more microsatellite instability sites(P=0.006). In addition,NEP-H subgroup was also characterized by higher chance to be involved in tumor clonal evolution [odds ratio(OR)=46.7, P<0.001]. Gene set enrichment analysis revealed that upregulation of MYC and its targets could suppress immune responses, leading to elevated neoantigen expression proportion in tumor cells. Furthermore, we discovered an immune escape mechanism that tumors could become more inconspicuous by evolving subclones with less immunogenicity. We observed that smaller clonal mutation clusters with higher immunogenicity in tumor were more likely to involve in clonal evolution. Based on identified neoantigen profiles, we also discovered series of neoantigenic hotspot genes, which could serve as potential actionable targets in future.Conclusions: Our results revealed the landscape of HCC neoantigens and discovered two clinically relevant subgroups with distinct neoantigen expression patterns, suggesting the neoantigen expression should be fully considered in future immunotherapeutic interventions. | Zhenli Li Geng Chen Zhixiong Cai Xiuqing Dong Lei He Liman Qiu Yongyi Zeng Xiaolong Liu Jingfeng Liu | 2021 | Chinese Journal of Cancer Research2021，33，3： | 3 |
| 2 | Promotion of cardiac differentiation of brown adipose derived stem cells by chitosan hydrogel for repair after myocardial infarction显示文摘 | Haibin Wang Jinxin Shi Yan Wang Yujing Yin Liman Wang Jianfeng Liu Zhiqiang Liu Cuimi Duan Ping Zhu Changyong Wang | 2014 | Biomaterials2014，，： | 2 |
| 3 | Dna computing on surfaces显示文摘 | Liu Q Liman W | 2000 | Nature2000，，403： | 1 |
| 4 | Object segmentation using ant colony optimization algorithm and fuzzy entropy显示文摘 | Tao Wenbing Jin Hai Liu Liman | 2007 | Pattern Recognition letters2007，28，7： | 1 |
| 5 | Intracellular Ca^2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5显示文摘 | Liu D Liman E R | 2003 | Proc Natl Acad Sci USA2003，100，15： | 1 |
| 6 | Dna computing on surfaces显示文摘 | Liu Q Liman W | 2000 | Nature2000，，403： | 1 |
| 7 | DNA computing on surfaces显示文摘 | Liman W | 2000 | Nature2000，，403： | 1 |
| 8 | Interactively multiple scenes segmentation based on variational formulation and graph cuts 显示文摘 | Tao Wenbing Chang Feng Liu Liman | 2010 | Pattern Recognition2010，43，10： | 1 |
| 9 | Object segmentation using ant colony optimization algorithm and fuzzy entropy显示文摘 | Tao Wenbing Jin Hai Liu Liman | 2007 | Pattern Recognition Letters2007，28，7： | 1 |
| 10 | DNA Computing on Surfaces显示文摘 | Liman W Frutos A | 2000 | Nature2000，403，： | 1 |
| 11 | An in vitro study on the dental caries preventing effect of oligomeric procyanidins in sorghum episperm 显示文摘 | XU Liman LIU Rui LI Duandan | 2011 | Food Chemistry2011，126，3： | 1 |
| 12 | DNA Computing on Surfaces显示文摘 | Liu Qinghua Wang Liman Frutos A G | 2000 | Nature2000，403，13： | 1 |
| 13 | DNA Computing on Surface 显示文摘 | Liu Qinghua Wang Liman Frutos A G | 2000 | Nature2000，403，13： | 1 |
| 14 | DNA computing on surfaces显示文摘 | Liman Wang Anthony G Frutos Anne E Condon Robert M Corn Lloyd M Smith | 2000 | Nature2000，403，13： | 1 |
| 15 | An in vitro study on the dentaJ caries preventing effect of oligomeric procyandins in sorghum episperm显示文摘 | XU LIMAN LIU RUI LI DUANDAN | 2011 | Food Chemistry2011，126，3： | 1 |
| 16 | DNA computing on surfaces显示文摘 | LIU QINGHUA LIMAN WANG ANTHONY G FRUTOS | | 0，，13： | 1 |
| 17 | Object segmentation using ant colony optimization algorithm and fuzzy entropy显示文摘 | Tao Wenbing Jin Hal Liu Liman | 2007 | Pattern Recognition Letters2007，28，7： | 1 |
| 18 | Intracellular Ca^2+ and the phospholipid PIP2 regulate the tastc transduction ion channel TRPM5显示文摘 | Liu D Liman ER | 2003 | Proc Natl Acad Sci U S A2003，100，15： | 1 |
| 19 | Dna Computing on Surfaces显示文摘 | Liu Q Liman W | 2000 | Nature2000，，403： | 1 |
| 20 | Silkworms culture as a source of protein for humans in space显示文摘 | Yunan Yang Liman Tang Ling Tong Hong Liu | 2008 | Advances in Space Research2008，，8： | 1 |
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