BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver, and becoming the third-leading cause of cancer-related mortality worldwide. Despite the immune checkpoint inhibitors and molecular targeted therapies have shown preferable efficacy in HCC, large number of HCC patients do not respond effectively to anti-PD-1 reagents. Besides, the accumulation of genetic mutations in cancer cells may lead to the therapy resistant. Hence, there are clinical gaps between genetic and transcriptomic biomarkers for the HCC treatment. METHODS: To investigate the genetic mapping of liver cancer, targeted deep sequencing (TDS) and bioinformatics analysis were performed on hepatocellular carcinoma (HCC) tumor tissues and matched blood samples. Furthermore, copy number variants (CNVs) and Tumor mutation burden (TMB) were calculated. Immunohistochemistry was applied to determine the PD-L1 expression in HCC tumor tissues. Clinical characteristic, PD-L1 expression, and the TMB were analyzed in 32 HCC patients. RESULTS: This study indicated that the PD-L1 positive patients exhibited a lower TMB compared to the PD-L1 negative group, and PD-L1 positive patients were more likely to suffer from aggressive clinicopathologic features than PD-L1 negative patients. We also verified the top 30 mutated genes, including TP53, CTNNB1, KMT2D, AXIN1, ALK, and NOTCH1, in our dataset. Our results indicated that PD-L1 positive patients possessed more tumors with vascular invasion and advanced CCLC stage. Moreover, PD-L1 positive patients exhibited a lower TMB compared to the PD-L1 negative group. CONCLUSIONS: These findings could improve our understanding of the effects of immune checkpoint therapies on prognosis, and could facilitate the monitoring of somatic mutations in HCC. 2021 Journal of Gastrointestinal Oncology. All rights reserved.
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver, and becoming the third-leading cause of cancer-related mortality worldwide. Despite the immune checkpoint inhibitors and molecular targeted therapies have shown preferable efficacy in HCC, large number of HCC patients do not respond effectively to anti-PD-1 reagents. Besides, the accumulation of genetic mutations in cancer cells may lead to the therapy resistant. Hence, there are clinical gaps between genetic and transcriptomic biomarkers for the HCC treatment. METHODS: To investigate the genetic mapping of liver cancer, targeted deep sequencing (TDS) and bioinformatics analysis were performed on hepatocellular carcinoma (HCC) tumor tissues and matched blood samples. Furthermore, copy number variants (CNVs) and Tumor mutation burden (TMB) were calculated. Immunohistochemistry was applied to determine the PD-L1 expression in HCC tumor tissues. Clinical characteristic, PD-L1 expression, and the TMB were analyzed in 32 HCC patients. RESULTS: This study indicated that the PD-L1 positive patients exhibited a lower TMB compared to the PD-L1 negative group, and PD-L1 positive patients were more likely to suffer from aggressive clinicopathologic features than PD-L1 negative patients. We also verified the top 30 mutated genes, including TP53, CTNNB1, KMT2D, AXIN1, ALK, and NOTCH1, in our dataset. Our results indicated that PD-L1 positive patients possessed more tumors with vascular invasion and advanced CCLC stage. Moreover, PD-L1 positive patients exhibited a lower TMB compared to the PD-L1 negative group. CONCLUSIONS: These findings could improve our understanding of the effects of immune checkpoint therapies on prognosis, and could facilitate the monitoring of somatic mutations in HCC. 2021 Journal of Gastrointestinal Oncology. All rights reserved.
Authors: Aaron McKenna; Matthew Hanna; Eric Banks; Andrey Sivachenko; Kristian Cibulskis; Andrew Kernytsky; Kiran Garimella; David Altshuler; Stacey Gabriel; Mark Daly; Mark A DePristo Journal: Genome Res Date: 2010-07-19 Impact factor: 9.043
Authors: Biao Liu; Jeffrey M Conroy; Carl D Morrison; Adekunle O Odunsi; Maochun Qin; Lei Wei; Donald L Trump; Candace S Johnson; Song Liu; Jianmin Wang Journal: Oncotarget Date: 2015-03-20
Authors: Jeffrey W Tyner; Cristina E Tognon; Daniel Bottomly; Beth Wilmot; Stephen E Kurtz; Samantha L Savage; Nicola Long; Anna Reister Schultz; Elie Traer; Melissa Abel; Anupriya Agarwal; Aurora Blucher; Uma Borate; Jade Bryant; Russell Burke; Amy Carlos; Richie Carpenter; Joseph Carroll; Bill H Chang; Cody Coblentz; Amanda d'Almeida; Rachel Cook; Alexey Danilov; Kim-Hien T Dao; Michie Degnin; Deirdre Devine; James Dibb; David K Edwards; Christopher A Eide; Isabel English; Jason Glover; Rachel Henson; Hibery Ho; Abdusebur Jemal; Kara Johnson; Ryan Johnson; Brian Junio; Andy Kaempf; Jessica Leonard; Chenwei Lin; Selina Qiuying Liu; Pierrette Lo; Marc M Loriaux; Samuel Luty; Tara Macey; Jason MacManiman; Jacqueline Martinez; Motomi Mori; Dylan Nelson; Ceilidh Nichols; Jill Peters; Justin Ramsdill; Angela Rofelty; Robert Schuff; Robert Searles; Erik Segerdell; Rebecca L Smith; Stephen E Spurgeon; Tyler Sweeney; Aashis Thapa; Corinne Visser; Jake Wagner; Kevin Watanabe-Smith; Kristen Werth; Joelle Wolf; Libbey White; Amy Yates; Haijiao Zhang; Christopher R Cogle; Robert H Collins; Denise C Connolly; Michael W Deininger; Leylah Drusbosky; Christopher S Hourigan; Craig T Jordan; Patricia Kropf; Tara L Lin; Micaela E Martinez; Bruno C Medeiros; Rachel R Pallapati; Daniel A Pollyea; Ronan T Swords; Justin M Watts; Scott J Weir; David L Wiest; Ryan M Winters; Shannon K McWeeney; Brian J Druker Journal: Nature Date: 2018-10-17 Impact factor: 49.962