DNA Damage Repair Status Predicts Opposite Clinical Prognosis Immunotherapy and Non-Immunotherapy in Hepatocellular Carcinoma

被引:18
作者
Chen, Yunfei [1 ,2 ,3 ,4 ]
Wang, Xu [5 ,6 ]
Deng, Xiaofan [1 ,2 ,3 ,4 ]
Zhang, Yu [1 ,2 ,3 ,4 ]
Liao, Rui [1 ,2 ,3 ,4 ]
Li, Youzan [1 ,2 ,3 ,4 ]
Yang, Hongji [1 ,2 ,3 ,4 ]
Chen, Kai [1 ,2 ,3 ,4 ]
机构
[1] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Hepatobiliary Surg 3, Chengdu, Peoples R China
[2] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Organ Transplant Ctr, Chengdu, Peoples R China
[3] Chinese Acad Sci, Sichuan Translat Med Res Hosp, Dept Hepatobiliary Surg 3, Chengdu, Peoples R China
[4] Chinese Acad Sci, Sichuan Translat Med Res Hosp, Organ Transplant Ctr, Chengdu, Peoples R China
[5] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Ward Hepatobiliary Surg 2, Chengdu, Peoples R China
[6] Chinese Acad Sci, Sichuan Translat Med Res Hosp, Ward Hepatobiliary Surg 2, Chengdu, Peoples R China
来源
FRONTIERS IN IMMUNOLOGY | 2021年 / 12卷
关键词
Immune checkpoint inhibitors; hepatocellular carcinoma; DNA damage repair; tumor microenvironment; immunotherapy; CONNECTIVITY MAP; EXPRESSION; SIGNATURES; CELLS; RESISTANCE; DISCOVERY; BLOCKADE; FEATURES; CANCERS; GENES;
D O I
10.3389/fimmu.2021.676922
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Immune checkpoint inhibitors(ICIs) that activate tumor-specific immune responses bring new hope for the treatment of hepatocellular carcinoma(HCC). However, there are still some problems, such as uncertain curative effects and low objective response rates, which limit the curative effect of immunotherapy. Therefore, it is an urgent problem to guide the use of ICIs in HCC based on molecular typing. We downloaded the The Cancer Genome Atlas-Liver hepatocellular carcinoma(TCGA-LIHC) and Mongolian-LIHC cohort. Unsupervised clustering was applied to the highly variable data regarding expression of DNA damage repair(DDR). The CIBERSORT was used to evaluate the proportions of immune cells. The connectivity map(CMap) and pRRophetic algorithms were used to predict the drug sensitivity. There were significant differences in DDR molecular subclasses in HCC(DDR1 and DDR2), and DDR1 patients had low expression of DDR-related genes, while DDR2 patients had high expression of DDR-related genes. Of the patients who received traditional treatment, DDR2 patients had significantly worse overall survival(OS) than DDR1 patients. In contrast, of the patients who received ICIs, DDR2 patients had significantly prolonged OS compared with DDR1 patients. Of the patients who received traditional treatment, patients with high DDR scores had worse OS than those with low DDR scores. However, the survival of patients with high DDR scores after receiving ICIs was significantly higher than that of patients with low DDR scores. The DDR scores of patients in the DDR2 group were significantly higher than those of patients in the DDR1 group. The tumor microenvironment(TME) of DDR2 patients was highly infiltrated by activated immune cells, immune checkpoint molecules and proinflammatory molecules and antigen presentation-related molecules. In this study, HCC patients were divided into the DDR1 and DDR2 group. Moreover, DDR status may serve as a potential biomarker to predict opposite clinical prognosis immunotherapy and non-immunotherapy in HCC.
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页数:14
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共 52 条
  • [1] Safranal induces DNA double-strand breakage and ER-stress-mediated cell death in hepatocellular carcinoma cells
    Al-Hrout, Ala'a
    Chaiboonchoe, Amphun
    Khraiwesh, Basel
    Murali, Chandraprabha
    Baig, Badriya
    El-Awady, Raafat
    Tarazi, Hamadeh
    Alzahmi, Amnah
    Nelson, David R.
    Greish, Yaser E.
    Ramadan, Wafaa
    Salehi-Ashtiani, Kourosh
    Amin, Amr
    [J]. SCIENTIFIC REPORTS, 2018, 8
  • [2] Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1
    Barbie, David A.
    Tamayo, Pablo
    Boehm, Jesse S.
    Kim, So Young
    Moody, Susan E.
    Dunn, Ian F.
    Schinzel, Anna C.
    Sandy, Peter
    Meylan, Etienne
    Scholl, Claudia
    Froehling, Stefan
    Chan, Edmond M.
    Sos, Martin L.
    Michel, Kathrin
    Mermel, Craig
    Silver, Serena J.
    Weir, Barbara A.
    Reiling, Jan H.
    Sheng, Qing
    Gupta, Piyush B.
    Wadlow, Raymond C.
    Le, Hanh
    Hoersch, Sebastian
    Wittner, Ben S.
    Ramaswamy, Sridhar
    Livingston, David M.
    Sabatini, David M.
    Meyerson, Matthew
    Thomas, Roman K.
    Lander, Eric S.
    Mesirov, Jill P.
    Root, David E.
    Gilliland, D. Gary
    Jacks, Tyler
    Hahn, William C.
    [J]. NATURE, 2009, 462 (7269) : 108 - U122
  • [3] The genomic landscape of Mongolian hepatocellular carcinoma
    Candia, Julian
    Bayarsaikhan, Enkhjargal
    Tandon, Mayank
    Budhu, Anuradha
    Forgues, Marshonna
    Tovuu, Lkhagva-Ochir
    Tudev, Undarmaa
    Lack, Justin
    Chao, Ann
    Chinburen, Jigjidsuren
    Wang, Xin Wei
    [J]. NATURE COMMUNICATIONS, 2020, 11 (01)
  • [4] Chen BB, 2018, METHODS MOL BIOL, V1711, P243, DOI 10.1007/978-1-4939-7493-1_12
  • [5] Corylin increases the sensitivity of hepatocellular carcinoma cells to chemotherapy through long noncoding RNA RAD51-AS1-mediated inhibition of DNA repair
    Chen, Chin-Chuan
    Chen, Chi-Yuan
    Ueng, Shir-Hwa
    Hsueh, Chuen
    Yeh, Chau-Ting
    Ho, Jar-Yi
    Chou, Li-Fang
    Wang, Tong-Hong
    [J]. CELL DEATH & DISEASE, 2018, 9
  • [6] TCGAbiolinks: an R/Bioconductor package for integrative analysis of TCGA data
    Colaprico, Antonio
    Silva, Tiago C.
    Olsen, Catharina
    Garofano, Luciano
    Cava, Claudia
    Garolini, Davide
    Sabedot, Thais S.
    Malta, Tathiane M.
    Pagnotta, Stefano M.
    Castiglioni, Isabella
    Ceccarelli, Michele
    Bontempi, Gianluca
    Noushmehr, Houtan
    [J]. NUCLEIC ACIDS RESEARCH, 2016, 44 (08) : e71
  • [7] Hepatocellular Carcinoma: The Role of Interventional Oncology
    Donadon, Matteo
    Solbiati, Luigi
    Dawson, Laura
    Barry, Aisling
    Sapisochin, Gonzalo
    Greig, Paul D.
    Shiina, Shuichiro
    Fontana, Andrea
    Torzilli, Guido
    [J]. LIVER CANCER, 2017, 6 (01) : 34 - 43
  • [8] Nanomedicinal strategies to treat multidrug-resistant tumors: current progress
    Dong, Xiaowei
    Mumper, Russell J.
    [J]. NANOMEDICINE, 2010, 5 (04) : 597 - 615
  • [9] Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial
    El-Khoueiry, Anthony B.
    Sangro, Bruno
    Yau, Thomas
    Crocenzi, Todd S.
    Kudo, Masatoshi
    Hsu, Chiun
    Kim, Tae-You
    Choo, Su-Pin
    Trojan, Jorg
    Welling, Theodore H., III
    Meyer, Tim
    Kang, Yoon-Koo
    Yeo, Winnie
    Chopra, Akhil
    Anderson, Jeffrey
    dela Cruz, Christine
    Lang, Lixin
    Neely, Jaclyn
    Tang, Hao
    Dastani, Homa B.
    Melero, Ignacio
    [J]. LANCET, 2017, 389 (10088) : 2492 - 2502
  • [10] Nivolumab for the treatment of hepatocellular carcinoma
    Finkelmeier, Fabian
    Waidmann, Oliver
    Trojan, Joerg
    [J]. EXPERT REVIEW OF ANTICANCER THERAPY, 2018, 18 (12) : 1169 - 1175