AUTHOR=Guo Chunguang , Liu Zaoqu , Yu Yin , Liu Shirui , Ma Ke , Ge Xiaoyong , Xing Zhe , Lu Taoyuan , Weng Siyuan , Wang Libo , Liu Long , Hua Zhaohui , Han Xinwei , Li Zhen 

TITLE=Integrated Analysis of Multi-Omics Alteration, Immune Profile, and Pharmacological Landscape of Pyroptosis-Derived lncRNA Pairs in Gastric Cancer

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.816153

DOI=10.3389/fcell.2022.816153

ISSN=2296-634X

ABSTRACT=<p><bold>Background:</bold> Recent evidence demonstrates that pyroptosis-derived long non-coding RNAs (lncRNAs) have profound impacts on the initiation, progression, and microenvironment of tumors. However, the roles of pyroptosis-derived lncRNAs (PDLs) in gastric cancer (GC) remain elusive.</p><p><bold>Methods:</bold> We comprehensively analyzed the multi-omics data of 839 GC patients from three independent cohorts. The previous gene set enrichment analysis embedding algorithm was utilized to identify PDLs. A gene pair pipeline was developed to facilitate clinical translation <italic>via</italic> qualitative relative expression orders. The LASSO algorithm was used to construct and validate a pyroptosis-derived lncRNA pair prognostics signature (PLPPS). The associations between PLPPS and multi-omics alteration, immune profile, and pharmacological landscape were further investigated.</p><p><bold>Results:</bold> A total of 350 PDLs and 61,075 PDL pairs in the training set were generated. Cox regression revealed 15 PDL pairs associated with overall survival, which were utilized to construct the PLPPS model <italic>via</italic> the LASSO algorithm. The high-risk group demonstrated adverse prognosis relative to the low-risk group. Remarkably, genomic analysis suggested that the lower tumor mutation burden and gene mutation frequency (e.g., <italic>TTN</italic>, <italic>MUC16</italic>, and <italic>LRP1B</italic>) were found in the high-risk group patients. The copy number variants were not significantly different between the two groups. Additionally, the high-risk group possessed lower immune cell infiltration abundance and might be resistant to a few chemotherapeutic drugs (including cisplatin, paclitaxel, and gemcitabine).</p><p><bold>Conclusion:</bold> PDLs were closely implicated in the biological process and prognosis of GC, and our PLPPS model could serve as a promising tool to advance prognostic management and personalized treatment of GC patients.</p>