Alternative Splicing-Based Differences Between Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: Genes, Immune Microenvironment, and Survival Prognosis

Alternative splicing (AS) event is a novel biomarker of tumor tumorigenesis and progression. However, the comprehensive analysis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) is lacking. Differentially expressed analysis was used to identify the differentially expressed...

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Main Authors: Dingan Luo, Deze Zhao, Mao Zhang, Chuan Hu, Haoran Li, Shun Zhang, Xiaowu Chen, Lakshmi Huttad, Bailiang Li, Cheng Jin, Changwei Lin, Bing Han
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-10-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.731993/full
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author Dingan Luo
Deze Zhao
Mao Zhang
Chuan Hu
Haoran Li
Shun Zhang
Xiaowu Chen
Lakshmi Huttad
Bailiang Li
Cheng Jin
Changwei Lin
Bing Han
author_facet Dingan Luo
Deze Zhao
Mao Zhang
Chuan Hu
Haoran Li
Shun Zhang
Xiaowu Chen
Lakshmi Huttad
Bailiang Li
Cheng Jin
Changwei Lin
Bing Han
author_sort Dingan Luo
collection DOAJ
description Alternative splicing (AS) event is a novel biomarker of tumor tumorigenesis and progression. However, the comprehensive analysis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) is lacking. Differentially expressed analysis was used to identify the differentially expressed alternative splicing (DEAS) events between HCC or ICC tissues and their normal tissues. The correlation between DEAS events and functional analyses or immune features was evaluated. The cluster analysis based on DEAS can accurately reflect the differences in the immune microenvironment between HCC and ICC. Forty-five immune checkpoints and 23 immune features were considered statistically significant in HCC, while only seven immune checkpoints and one immune feature in ICC. Then, the prognostic value of DEAS events was studied, and two transcripts with different basic cell functions (proliferation, cell cycle, invasion, and migration) were produced by ADHFE1 through alternative splicing. Moreover, four nomograms were established in conjunction with relevant clinicopathological factors. Finally, we found two most significant splicing factors and further showed their protein crystal structure. The joint analysis of the AS events in HCC and ICC revealed novel insights into immune features and clinical prognosis, which might provide positive implications in HCC and ICC treatment.
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spelling doaj.art-0b0dd45d5f7b4a66bca3d7a9d2053cc42022-12-21T19:20:27ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-10-011110.3389/fonc.2021.731993731993Alternative Splicing-Based Differences Between Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: Genes, Immune Microenvironment, and Survival PrognosisDingan Luo0Deze Zhao1Mao Zhang2Chuan Hu3Haoran Li4Shun Zhang5Xiaowu Chen6Lakshmi Huttad7Bailiang Li8Cheng Jin9Changwei Lin10Bing Han11Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, ChinaMedical College, Qingdao University, Qingdao, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, ChinaAsian Liver Center, Department of Surgery, Medical School of Stanford University, Stanford, CA, United StatesAsian Liver Center, Department of Surgery, Medical School of Stanford University, Stanford, CA, United StatesDepartment of Radiation Oncology, Medical School of Stanford University, Stanford, CA, United StatesDepartment of Radiation Oncology, Medical School of Stanford University, Stanford, CA, United StatesDepartment of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, ChinaAlternative splicing (AS) event is a novel biomarker of tumor tumorigenesis and progression. However, the comprehensive analysis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) is lacking. Differentially expressed analysis was used to identify the differentially expressed alternative splicing (DEAS) events between HCC or ICC tissues and their normal tissues. The correlation between DEAS events and functional analyses or immune features was evaluated. The cluster analysis based on DEAS can accurately reflect the differences in the immune microenvironment between HCC and ICC. Forty-five immune checkpoints and 23 immune features were considered statistically significant in HCC, while only seven immune checkpoints and one immune feature in ICC. Then, the prognostic value of DEAS events was studied, and two transcripts with different basic cell functions (proliferation, cell cycle, invasion, and migration) were produced by ADHFE1 through alternative splicing. Moreover, four nomograms were established in conjunction with relevant clinicopathological factors. Finally, we found two most significant splicing factors and further showed their protein crystal structure. The joint analysis of the AS events in HCC and ICC revealed novel insights into immune features and clinical prognosis, which might provide positive implications in HCC and ICC treatment.https://www.frontiersin.org/articles/10.3389/fonc.2021.731993/fullhepatocellular carcinomaintrahepatic cholangiocarcinomaalternative splicingimmuneprognostic models
spellingShingle Dingan Luo
Deze Zhao
Mao Zhang
Chuan Hu
Haoran Li
Shun Zhang
Xiaowu Chen
Lakshmi Huttad
Bailiang Li
Cheng Jin
Changwei Lin
Bing Han
Alternative Splicing-Based Differences Between Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: Genes, Immune Microenvironment, and Survival Prognosis
Frontiers in Oncology
hepatocellular carcinoma
intrahepatic cholangiocarcinoma
alternative splicing
immune
prognostic models
title Alternative Splicing-Based Differences Between Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: Genes, Immune Microenvironment, and Survival Prognosis
title_full Alternative Splicing-Based Differences Between Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: Genes, Immune Microenvironment, and Survival Prognosis
title_fullStr Alternative Splicing-Based Differences Between Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: Genes, Immune Microenvironment, and Survival Prognosis
title_full_unstemmed Alternative Splicing-Based Differences Between Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: Genes, Immune Microenvironment, and Survival Prognosis
title_short Alternative Splicing-Based Differences Between Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: Genes, Immune Microenvironment, and Survival Prognosis
title_sort alternative splicing based differences between hepatocellular carcinoma and intrahepatic cholangiocarcinoma genes immune microenvironment and survival prognosis
topic hepatocellular carcinoma
intrahepatic cholangiocarcinoma
alternative splicing
immune
prognostic models
url https://www.frontiersin.org/articles/10.3389/fonc.2021.731993/full
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