Pan-cancer analysis of BRK1 as a potential immunotherapeutic target.

Increasing evidence supports the connection between the progression of several cancers and BRK1. However, the clinical significance of aberrant BRK1 gene expression in cancer is unknown. This study is conducted to investigate the possibility and effect of BRK1 as a potential immunotherapy target, to deliver a better option for liver cancer immunotherapy. We explored the predictive role of BRK1 expression in a variety of cancers from different bioinformatics, including differential expression in different cancers, tumor microenvironment (TME), microsatellite instability (MSI), tumor mutational burden (TMB), immune checkpoint molecules, immune-related and cell cycle-related signalling pathways, and drug response sensitivity. Finally, we verified the expression of BRK1 in hepatocellular carcinoma using immunohistochemistry. BRK1 is overexpressed in multiple cancers and displays a negative association with prognosis and progression of disease in a wide range of main cancer types. Additionally, the expression of BRK1 is related to MSI and TMB of tumors. There was also a remarkable correlation between the expression of BRK1 and immune score, immune infiltration, immune checkpoint molecules and a stromal score of tumors. In hepatocellular carcinoma, BRK1 is associated with several signaling pathways and immune cell infiltration may affect several key immune-related regulatory genes, making it an excellent biomarker and may be a sensitive target for immune drugs.Our research suggests that BRK1 may be a potential prognostic marker and target for immunotherapy and may be associated with poor prognosis in diverse malignancies, including hepatocellular carcinoma.

[1]  Yumei Fan,et al.  Pan-Cancer Analysis of the Prognostic and Immunological Role of HSF1: A Potential Target for Survival and Immunotherapy , 2021, Oxidative medicine and cellular longevity.

[2]  A. Ben-Baruch Tumor Necrosis Factor α: Taking a Personalized Road in Cancer Therapy , 2022, Frontiers in Immunology.

[3]  Jia Liu,et al.  A TNFR2 antibody by countering immunosuppression cooperates with HMGN1 and R848 immune stimulants to inhibit murine colon cancer. , 2021, International immunopharmacology.

[4]  S. Ro,et al.  c-Myc-driven Hepatocarcinogenesis , 2021, AntiCancer Research.

[5]  A. Jemal,et al.  Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries , 2021, CA: a cancer journal for clinicians.

[6]  A. Cervantes,et al.  Hepatocellular carcinoma , 2021, Nature Reviews Disease Primers.

[7]  Jiang Ren,et al.  Targeting TGFβ signal transduction for cancer therapy , 2021, Signal Transduction and Targeted Therapy.

[8]  Jingjing Wu,et al.  Prognostic value and immunological role of PDCD1 gene in pan-cancer. , 2020, International immunopharmacology.

[9]  Q. Ju,et al.  NFE2L2 Is a Potential Prognostic Biomarker and Is Correlated with Immune Infiltration in Brain Lower Grade Glioma: A Pan-Cancer Analysis , 2020, Oxidative medicine and cellular longevity.

[10]  Zemin Zhang,et al.  The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications , 2020, Cellular & Molecular Immunology.

[11]  N. Curtin,et al.  DNA damage checkpoint kinases in cancer , 2020, Expert Reviews in Molecular Medicine.

[12]  J. Wolchok,et al.  The future of cancer immunotherapy: microenvironment-targeting combinations , 2020, Cell Research.

[13]  Angela N. Brooks,et al.  Visualizing and interpreting cancer genomics data via the Xena platform , 2020, Nature Biotechnology.

[14]  I. Witz,et al.  The Tumor Microenvironment , 2012 .

[15]  P. Allavena,et al.  Current Strategies to Target Tumor-Associated-Macrophages to Improve Anti-Tumor Immune Responses , 2019, Cells.

[16]  Beibei Ru,et al.  TISIDB: an integrated repository portal for tumor-immune system interactions , 2019, Bioinform..

[17]  N. Meyer,et al.  The TNF Paradox in Cancer Progression and Immunotherapy , 2019, Front. Immunol..

[18]  Hiroyuki Yamamoto,et al.  An updated review of microsatellite instability in the era of next-generation sequencing and precision medicine. , 2019, Seminars in oncology.

[19]  A. Jemal,et al.  Cancer statistics, 2019 , 2019, CA: a cancer journal for clinicians.

[20]  B. Sheridan,et al.  Tissue Adaptations of Memory and Tissue-Resident Gamma Delta T Cells , 2018, Front. Immunol..

[21]  C. Hetz,et al.  Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease. , 2018, Journal of hepatology.

[22]  T. Nagase,et al.  TGF-β Signaling in Lung Health and Disease , 2018, International journal of molecular sciences.

[23]  T. Lahusen,et al.  Gamma Delta T Cell Therapy for Cancer: It Is Good to be Local , 2018, Front. Immunol..

[24]  J. Massagué,et al.  Contextual determinants of TGFβ action in development, immunity and cancer , 2018, Nature Reviews Molecular Cell Biology.

[25]  Xuedong Zhou,et al.  Transforming growth factor-β in stem cells and tissue homeostasis , 2018, Bone Research.

[26]  Yoshinobu Nakanishi,et al.  Induction of Apoptosis and Subsequent Phagocytosis of Virus-Infected Cells As an Antiviral Mechanism , 2017, Front. Immunol..

[27]  J. Maris,et al.  11q deletion in neuroblastoma: a review of biological and clinical implications , 2017, Molecular Cancer.

[28]  Yu Liu,et al.  Neutralization of TNFα in tumor with a novel nanobody potentiates paclitaxel-therapy and inhibits metastasis in breast cancer. , 2017, Cancer letters.

[29]  Younis Hazari,et al.  Emerging tale of UPR and cancer: an essentiality for malignancy , 2016, Tumor Biology.

[30]  A. Nicholson,et al.  A Validation Study for the Use of ROS1 Immunohistochemical Staining in Screening for ROS1 Translocations in Lung Cancer , 2016, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[31]  L. Zitvogel,et al.  Targeting the tumor microenvironment: removing obstruction to anticancer immune responses and immunotherapy. , 2016, Annals of oncology : official journal of the European Society for Medical Oncology.

[32]  Ash A. Alizadeh,et al.  Abstract PR09: The prognostic landscape of genes and infiltrating immune cells across human cancers , 2015 .

[33]  Ash A. Alizadeh,et al.  Robust enumeration of cell subsets from tissue expression profiles , 2015, Nature Methods.

[34]  Kaitai Zhang,et al.  Sp1 transcriptionally regulates BRK1 expression in non-small cell lung cancer cells. , 2014, Gene.

[35]  J. W. Brewer,et al.  Regulatory crosstalk within the mammalian unfolded protein response , 2014, Cellular and Molecular Life Sciences.

[36]  H. Schreiber,et al.  Innate and adaptive immune cells in the tumor microenvironment , 2013, Nature Immunology.

[37]  Susan M. Kaech,et al.  Transcriptional control of effector and memory CD8+ T cell differentiation , 2012, Nature Reviews Immunology.

[38]  C. Sautès-Fridman,et al.  The immune contexture in human tumours: impact on clinical outcome , 2012, Nature Reviews Cancer.

[39]  A. Sudo,et al.  TNF inhibitor suppresses bone metastasis in a breast cancer cell line. , 2011, Biochemical and biophysical research communications.

[40]  Chien-Ru Liu,et al.  Targeting c-Myc as a novel approach for hepatocellular carcinoma. , 2010, World journal of hepatology.

[41]  Yong-jie Lu,et al.  Metastatic potential of lung squamous cell carcinoma associated with HSPC300 through its interaction with WAVE2. , 2009, Lung cancer.

[42]  F. Balkwill Tumour necrosis factor and cancer , 2009, Nature Reviews Cancer.

[43]  M. Schröder Endoplasmic reticulum stress responses , 2008, Cellular and Molecular Life Sciences.

[44]  Lin Feng,et al.  Identification of genes differentially expressed in human primary lung squamous cell carcinoma. , 2007, Lung cancer.

[45]  Shiro Suetsugu,et al.  The WASP–WAVE protein network: connecting the membrane to the cytoskeleton , 2007, Nature Reviews Molecular Cell Biology.

[46]  T. Stradal,et al.  Protein complexes regulating Arp2/3-mediated actin assembly. , 2006, Current opinion in cell biology.

[47]  S. Thorgeirsson,et al.  Application of comparative functional genomics to identify best-fit mouse models to study human cancer , 2004, Nature Genetics.

[48]  Kaitai Zhang,et al.  Identification of differentially expressed genes in human lung squamous cell carcinoma using suppression subtractive hybridization. , 2004, Cancer letters.

[49]  A. Helenius,et al.  Roles of N-linked glycans in the endoplasmic reticulum. , 2004, Annual review of biochemistry.

[50]  S. Gygi,et al.  Purification and architecture of the ubiquitous Wave complex. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[51]  Stella Pelengaris,et al.  c-MYC: more than just a matter of life and death , 2002, Nature Reviews Cancer.

[52]  Alexandre V. Podtelejnikov,et al.  Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck , 2002, Nature.