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CTRP and PRISM were applied to identify drugs targeting HPDL in LUAD. Functional loss-of-function experiments examined effects on LUAD proliferation and movement, linking HPDL with immune stimulation, immune-cell infiltration, and immunoregulator expression. HPDL additionally predicts responses to anti-PD1/anti-PDL1 therapy, supporting its use as a positive predictive biomarker for immune checkpoint inhibitor outcomes.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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\n4-Hydroxyphenylpyruvate Dioxygenase-Like predicts the prognosis and the immunotherapy response of cancers: a pan-cancer analysis  \nHuimin Li 1,*, Junzhi Liu2,*, Shurui Wang3,*, Yue Xu1, Qiang Tang4, Guoguang Ying1  \n1 Laboratory of Cancer Cell Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China  \n2 Department of Otorhinolaryngology, Tianjin Medical University General Hospital, Tianjin 300070, China 3Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China  \n4The Second Affiliated Hospital of Zhejiang University School Medicine, Hang Zhou 310000, China  \n* Equal contribution  \nCorrespondence to: Qiang Tang, Guoguang Ying; email: [tangqiang678@zju.edu.cn](tangqiang678@zju.edu.cn), [yingguoguang@tmu.edu.cn](yingguoguang@tmu.edu.cn)[ ](yingguoguang@tmu.edu.cn)[Keywords:](Keywords: 4-Hydroxyphenylpyruvate Dioxygenase-Like)[ 4-Hydroxyphenylpyruvate Dioxygenase-Like](Keywords: 4-Hydroxyphenylpyruvate Dioxygenase-Like), pan-cancer, prognostic biomarker, immunotherapy response, proliferation  \nReceived: August 10, 2023 Accepted: December 1, 2023 Published: March 6, 2024  \nCopyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.  \nABSTRACT  \nThe 4-Hydroxyphenylpyruvate Dioxygenase-Like (HPDL) protein plays a crucial role in safeguarding cells from oxidative stress by orchestrating metabolic reprogramming. New research suggests that HPDL is considerably increased in pancreatic ductal adenocarcinoma, although its impact on cancer immunotherapy is still unclear. Pancancer transcriptional data were obtained from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression datasets. The cBioPortal webtool was utilized to examine genomic changes in different cancer types. The prognostic significance of HPDL in pancancer was evaluated using univariate Cox regression analysis. Extensive utilization of the CTRP and PRISM databases was performed to forecast potential medications that specifically target HPDL in LUAD. In summary, studies were conducted to evaluate the impact of HPDL on the proliferation and movement of LUAD cells using loss-of-function experiments. HPDL is expressed excessively ina wide variety of cancer types, indicating its prognostic and predictive value. Moreover, we emphasized the strong correlation between HPDL and indicators of immune stimulation, infiltration of immune cells, and expression of immunoregulators. The remarkable finding of the HPDL was its capacity to precisely anticipate responses to cancer therapies using anti-PDL1 and anti-PD1 antibodies among individuals. Moreover, HPDL can function as a predictive marker for specific inhibitors in instances of cancer. Suppression of HPDL resulted in reduced growth and movement of LUAD cells. To summarize, our results suggest that HPDL acts as a prospective predictor of outcomes and a positive indication of response to immunotherapy in patients undergoing treatment with immune checkpoint inhibitors (ICIs).  \nINTRODUCTION  \nThe reprogramming of energy metabolism, which facilitates rapid cellular growth and proliferation through the adjustment of energy metabolism pathways, has emerged as a defining characteristic of cancer [1] . Due to their heterogeneity and complex structure, tumor cells engage in diverse metabolic pathways. They not  \nonly metabolize glucose to generate ATP but also utilize other substrates such as glutamine, serine, arginine, fatty acids, and various lipid compounds to fuel their rapid proliferation [2] . According to recent research, HPDL protects cells from oxidative stress by changing the metabolic profile of cancer cells, giving pr","cbCaisOexy8xQE9H","https://ap.wps.com/l/cbCaisOexy8xQE9H","pdf",2865610,21,"English","# Abstract\n# Introduction\n## Cancer metabolism reprogramming\n## HPDL links to oxidative stress and glutamine metabolism\n## HPDL in pancreatic ductal adenocarcinoma models\n## Clinical implications and immune-related associations","[{\"question\":\"What biological role does HPDL have in cells?\",\"answer\":\"HPDL protects cells from oxidative stress by coordinating metabolic reprogramming, with evidence pointing to prioritization of glutamine metabolism.\"},{\"question\":\"How was HPDL evaluated for prognosis across cancers?\",\"answer\":\"Pancancer datasets from TCGA and GTEx were analyzed, genomic changes were explored using cBioPortal, and prognostic significance was assessed with univariate Cox regression.\"},{\"question\":\"How does HPDL relate to immunotherapy response?\",\"answer\":\"HPDL expression is correlated with immune stimulation, immune-cell infiltration, and immunoregulator expression, and it can precisely predict responses to anti-PD1 and anti-PDL1 antibodies.\"}]","4-Hydroxyphenylpyruvate Dioxygenase-Like predicts the prognosis and the immunotherapy response of cancers: a pan-cancer analysis | PDF",1789988255,53]