{"title":"PITPNC1 在肺腺癌中的作用:差异表达、免疫渗透和预后意义","authors":"Chao Li, Junsong Chen, Ganggang Zhang, Fang Guo, Xin Zhang","doi":"10.1101/2024.08.18.24312183","DOIUrl":null,"url":null,"abstract":"Lung adenocarcinoma (LUAD) is one of the most prevalent and deadly forms of lung cancer, necessitating the identification of novel biomarkers for diagnosis and prognosis. This study aims to explore the differential expression, diagnostic potential, underlying mechanisms, and clinical significance of PITPNC1 (phosphatidylinositol transfer protein, cytoplasmic 1) in LUAD.We utilized data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, comprising 530 LUAD samples and 59 control samples from TCGA-LUAD, as well as GSE10072 and GSE75037 datasets with a total of 224 samples. Data preprocessing included normalization to Fragments Per Kilobase of transcript per Million mapped reads (FPKM) format and batch effect correction using the R package sva. Differential gene expression analysis was performed using DESeq2 for TCGA-LUAD and limma for GEO datasets. Receiver Operating Characteristic (ROC) curve analysis was conducted to assess the diagnostic efficacy of PITPNC1.Our results revealed that PITPNC1 is significantly overexpressed in LUAD samples compared to controls (p < 0.001 in TCGA-LUAD; p < 0.01 in GEO). However, ROC curve analysis indicated moderate diagnostic accuracy with Area Under Curve (AUC) values between 0.5 and 0.7. Differential expression analysis identified 3838 genes associated with PITPNC1 expression, which were further subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. These genes were enriched in pathways related to external stimulus response, hormone level regulation, nitrogen metabolism, and neuroactive ligand-receptor interaction.Gene Set Enrichment Analysis (GSEA) highlighted significant enrichment in IL12 signaling pathway, Notch signaling pathway, MAPK6/MAPK4 signaling pathway, and Hedgehog On State pathway. Immune infiltration analysis using single-sample Gene Set Enrichment Analysis (ssGSEA) showed significant differences in five immune cell types between high and low PITPNC1 expression groups. Cox regression analysis indicated that PITPNC1 expression along with clinical stages are significant predictors of overall survival in LUAD patients.In conclusion, our comprehensive bioinformatics analysis underscores the potential role of PITPNC1 as a biomarker for LUAD diagnosis and prognosis.","PeriodicalId":501437,"journal":{"name":"medRxiv - Oncology","volume":"10 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Role of PITPNC1 in Lung Adenocarcinoma: Differential Expression, Immune Infiltration, and Prognostic Significance\",\"authors\":\"Chao Li, Junsong Chen, Ganggang Zhang, Fang Guo, Xin Zhang\",\"doi\":\"10.1101/2024.08.18.24312183\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Lung adenocarcinoma (LUAD) is one of the most prevalent and deadly forms of lung cancer, necessitating the identification of novel biomarkers for diagnosis and prognosis. This study aims to explore the differential expression, diagnostic potential, underlying mechanisms, and clinical significance of PITPNC1 (phosphatidylinositol transfer protein, cytoplasmic 1) in LUAD.We utilized data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, comprising 530 LUAD samples and 59 control samples from TCGA-LUAD, as well as GSE10072 and GSE75037 datasets with a total of 224 samples. Data preprocessing included normalization to Fragments Per Kilobase of transcript per Million mapped reads (FPKM) format and batch effect correction using the R package sva. Differential gene expression analysis was performed using DESeq2 for TCGA-LUAD and limma for GEO datasets. Receiver Operating Characteristic (ROC) curve analysis was conducted to assess the diagnostic efficacy of PITPNC1.Our results revealed that PITPNC1 is significantly overexpressed in LUAD samples compared to controls (p < 0.001 in TCGA-LUAD; p < 0.01 in GEO). However, ROC curve analysis indicated moderate diagnostic accuracy with Area Under Curve (AUC) values between 0.5 and 0.7. Differential expression analysis identified 3838 genes associated with PITPNC1 expression, which were further subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. These genes were enriched in pathways related to external stimulus response, hormone level regulation, nitrogen metabolism, and neuroactive ligand-receptor interaction.Gene Set Enrichment Analysis (GSEA) highlighted significant enrichment in IL12 signaling pathway, Notch signaling pathway, MAPK6/MAPK4 signaling pathway, and Hedgehog On State pathway. Immune infiltration analysis using single-sample Gene Set Enrichment Analysis (ssGSEA) showed significant differences in five immune cell types between high and low PITPNC1 expression groups. Cox regression analysis indicated that PITPNC1 expression along with clinical stages are significant predictors of overall survival in LUAD patients.In conclusion, our comprehensive bioinformatics analysis underscores the potential role of PITPNC1 as a biomarker for LUAD diagnosis and prognosis.\",\"PeriodicalId\":501437,\"journal\":{\"name\":\"medRxiv - Oncology\",\"volume\":\"10 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-08-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"medRxiv - Oncology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1101/2024.08.18.24312183\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"medRxiv - Oncology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.08.18.24312183","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
肺腺癌(LUAD)是最常见、最致命的肺癌之一,因此有必要鉴定用于诊断和预后的新型生物标志物。本研究旨在探讨PITPNC1(磷脂酰肌醇转运蛋白,胞质1)在LUAD中的差异表达、诊断潜力、潜在机制和临床意义。我们利用了癌症基因组图谱(TCGA)和基因表达总库(GEO)数据库中的数据,包括TCGA-LUAD中的530个LUAD样本和59个对照样本,以及GSE10072和GSE75037数据集共224个样本。数据预处理包括归一化为每百万映射读数转录本每千碱基片段(FPKM)格式,并使用 R 软件包 sva 进行批次效应校正。对 TCGA-LUAD 数据集使用 DESeq2 进行差异基因表达分析,对 GEO 数据集使用 limma 进行差异基因表达分析。我们的结果显示,与对照组相比,PITPNC1在LUAD样本中显著过表达(在TCGA-LUAD中为p < 0.001;在GEO中为p < 0.01)。然而,ROC 曲线分析表明诊断准确性适中,曲线下面积(AUC)值介于 0.5 和 0.7 之间。差异表达分析确定了 3838 个与 PITPNC1 表达相关的基因,并进一步对这些基因进行了基因本体(GO)和京都基因组百科全书(KEGG)富集分析。基因组富集分析(Gene Set Enrichment Analysis,GSEA)强调了IL12信号通路、Notch信号通路、MAPK6/MAPK4信号通路和刺猬状态通路的显著富集。利用单样本基因组富集分析(ssGSEA)进行的免疫浸润分析表明,PITPNC1表达量高的组别与表达量低的组别在五种免疫细胞类型上存在显著差异。Cox回归分析表明,PITPNC1的表达和临床分期是预测LUAD患者总生存期的重要指标。
The Role of PITPNC1 in Lung Adenocarcinoma: Differential Expression, Immune Infiltration, and Prognostic Significance
Lung adenocarcinoma (LUAD) is one of the most prevalent and deadly forms of lung cancer, necessitating the identification of novel biomarkers for diagnosis and prognosis. This study aims to explore the differential expression, diagnostic potential, underlying mechanisms, and clinical significance of PITPNC1 (phosphatidylinositol transfer protein, cytoplasmic 1) in LUAD.We utilized data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, comprising 530 LUAD samples and 59 control samples from TCGA-LUAD, as well as GSE10072 and GSE75037 datasets with a total of 224 samples. Data preprocessing included normalization to Fragments Per Kilobase of transcript per Million mapped reads (FPKM) format and batch effect correction using the R package sva. Differential gene expression analysis was performed using DESeq2 for TCGA-LUAD and limma for GEO datasets. Receiver Operating Characteristic (ROC) curve analysis was conducted to assess the diagnostic efficacy of PITPNC1.Our results revealed that PITPNC1 is significantly overexpressed in LUAD samples compared to controls (p < 0.001 in TCGA-LUAD; p < 0.01 in GEO). However, ROC curve analysis indicated moderate diagnostic accuracy with Area Under Curve (AUC) values between 0.5 and 0.7. Differential expression analysis identified 3838 genes associated with PITPNC1 expression, which were further subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. These genes were enriched in pathways related to external stimulus response, hormone level regulation, nitrogen metabolism, and neuroactive ligand-receptor interaction.Gene Set Enrichment Analysis (GSEA) highlighted significant enrichment in IL12 signaling pathway, Notch signaling pathway, MAPK6/MAPK4 signaling pathway, and Hedgehog On State pathway. Immune infiltration analysis using single-sample Gene Set Enrichment Analysis (ssGSEA) showed significant differences in five immune cell types between high and low PITPNC1 expression groups. Cox regression analysis indicated that PITPNC1 expression along with clinical stages are significant predictors of overall survival in LUAD patients.In conclusion, our comprehensive bioinformatics analysis underscores the potential role of PITPNC1 as a biomarker for LUAD diagnosis and prognosis.