Discover. Oncology最新文献

{"title":"Microplastics: a cancer-causing agent for humans and prospects for identification using AI and modern approaches.","authors":"Anshika, Amulya Jindal, Deepak Tomar, Mainuddin, Anoop Kumar","doi":"10.1007/s12672-024-01634-5","DOIUrl":"10.1007/s12672-024-01634-5","url":null,"abstract":"","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"367"},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An innovative glutamine metabolism-related gene signature for predicting prognosis and immune landscape in cervical cancer.","authors":"Hai-Ya Fang, Li-Mei Ji, Cui-Hua Hong","doi":"10.1007/s12672-025-02109-x","DOIUrl":"10.1007/s12672-025-02109-x","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer (CC) is a major global malignancy affecting women. However, the precise mechanisms underlying glutamine's role in CC remain inadequately understood. This study systematically assessed the survival outcomes, immune landscape, and drug sensitivity profiles with CC patients by analyzing genes associated with glutamine metabolism.</p><p><strong>Methods: </strong>Transcriptomic data for the samples were sourced from the TCGA, GTEx, and GEO databases. Prognostic genes were identified through univariate, multivariate, and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses. The predictive accuracy of the model was assessed through the analysis of receiver operating characteristic (ROC) curves. A comprehensive nomogram was developed and evaluated for accuracy using calibration and Decision Curve Analysis (DCA) curves. Kaplan-Meier (K-M) survival curves were employed to estimate overall survival. The relationship between risk scores and immune infiltration was analyzed through Single-sample Gene Set Enrichment Analysis (ssGSEA) and CIBERSORT. Functional enrichment analysis and the construction of miRNA and transcription factors networks were conducted to explore the potential molecular mechanisms of the signature genes.</p><p><strong>Results: </strong>This investigation identified four signature genes associated with glutamine metabolism, UCP2, LEPR, TFRC, and RNaseH2A. We successfully developed a prognostic model with strong predictive performance. In the training set, the AUC values for 1-, 3-, and 5-year survival were 0.702, 0.719, and 0.721, respectively. In the validation set, the AUC values for these time points were 0.715, 0.696, and 0.739, respectively. Patients categorized as low-risk had notably improved survival rates than those identified as high-risk (P < 0.05). Additionally, a nomogram that combines clinical data and risk scores offered improved clinical net benefits over a broad range of threshold probabilities. Functional enrichment analysis revealed that these signature genes are strongly linked to the regulation of the cell cycle and intracellular oxygen levels. Furthermore, the gene signature displayed a significant negative correlation with the infiltration levels of most immune cell types.</p><p><strong>Conclusion: </strong>This novel signature demonstrates robust predictive capability for prognostic survival probabilities and immune infiltration in CC patients, providing a fresh perspective for advancing precision treatment strategies in CC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"368"},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tanshinone IIA affects the proliferation of A549/Tax by affecting the expression of MMP7 through the PI3K-AKT-mTOR signaling pathway.","authors":"Fangjun Chen, Wenqiong Xiang, Guangliang Qiang","doi":"10.1007/s12672-025-02152-8","DOIUrl":"10.1007/s12672-025-02152-8","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to explore whether tanshinone IIA can act on paclitaxel-resistant non-small cell lung cancer A549/Tax and analyze the possible mechanisms involved.</p><p><strong>Methods: </strong>Using the Cell Counting Kit-8 (CCK-8), we preliminarily analyzed whether tanshinone IIA has an inhibitory effect on A549/Tax cells. We utilized public datasets, self-collected transcriptome datasets, and drug target analysis to identify potential targets. We employed real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) to detect the expression of core genes before and after drug treatment to analyze potential target genes and validated them using data from The Cancer Genome Atlas (TCGA). We conducted enrichment analysis on co-expressed genes of the target genes to explore potential mechanisms. Furthermore, we employed molecular docking and western blot to verify the possible mechanisms involved.</p><p><strong>Results: </strong>The CCK8 results indicated that tanshinone IIA has a significant inhibitory effect on A549/Tax cells. The qPCR results and the analysis of TCGA data indicated that MMP7 is the target gene. Enrichment results of MMP7 co-expressed genes suggested that the PI3K-AKT signaling pathway might play a key role. Molecular docking results indicated that tanshinone IIA has strong binding activity with PI3K, AKT, mTOR, and MMP7. Western blotting results showed that tanshinone IIA might inhibit MMP7 through the PI3K-AKT-mTOR signaling pathway.</p><p><strong>Conclusions: </strong>Tanshinone IIA may affect the proliferation of A549/Tax by influencing the expression of MMP7 through the PI3K-AKT-mTOR signaling pathway.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"369"},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PRSS53 is a potential novel biomarker related to prognosis and immunity in clear cell renal cell carcinoma.","authors":"Jiajun Zhang, Guocheng Liu, Wei Wang","doi":"10.1007/s12672-025-02114-0","DOIUrl":"10.1007/s12672-025-02114-0","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the expression levels, clinical significance, Immune infiltration and prognostic value of PRSS53 (Protease Serine 53) in clear cell renal cell carcinoma (ccRCC) using bioinformatics methods.</p><p><strong>Methods: </strong>Data on PRSS53 in ccRCC were extracted from databases and platforms, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), The Gene Expression Omnibus (GEO), Xiantao Academic Tool, Human Protein Atlas (HPA) and so on. We analyzed the relationship between PRSS53 expression and the clinical and pathological characteristics, diagnosis, immune infiltration and prognosis in ccRCC patients. Additionally, immunohistochemical analysis was performed on 9 pairs of ccRCC patient samples.</p><p><strong>Results: </strong>PRSS53 was significantly upregulated in ccRCC and was closely associated with the TNM stage and histological grade of ccRCC. Receiver operating characteristic (ROC) curve analysis demonstrated the excellent diagnostic performance of PRSS53 in ccRCC (AUC = 0.928). Patients with high PRSS53 expression exhibited lower overall survival (OS) and disease-specific survival (DSS). Gene set enrichment analysis (GSEA) revealed that PRSS53 is involved in cellular functions such as anchored component of membrane, basement membrane and RNA-binding involved in post-transcriptional gene silencing. Single-sample GSEA (ssGSEA) indicated a positive correlation between PRSS53 expression and T helper cells infiltration levels, and a negative correlation with T gamma delta (Tgd) cell infiltration. PRSS53 was predominantly expressed in renal proximal tubules. The immunohistochemical results and HPA database showed that PRSS53 protein expression was significantly lower in clinical ccRCC tissues  compared to normal tissues.</p><p><strong>Conclusion: </strong>PRSS53 is a new prognostic biomarker and potential therapeutic target for ccRCC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"362"},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Citrus flavonoids for overcoming breast cancer resistance to methotrexate: identification of potential targets of nobiletin and sinensetin.","authors":"Adam Hermawan, Naufa Hanif, Dyaningtyas Dewi Pamungkas Putri, Nurul Fatimah, Heri Himawan Prasetio","doi":"10.1007/s12672-025-02116-y","DOIUrl":"10.1007/s12672-025-02116-y","url":null,"abstract":"<p><p>Breast cancer is a potentially fatal illness that affects millions of women worldwide. Methotrexate (MTX) may be beneficial for treating breast cancer; however, high doses and prolonged use can cause drug resistance. Although certain citrus flavonoids-nobiletin, sinensetin, tangeretin, hesperidin, hesperetin, and naringenin-may overcome resistance to chemotherapy, no study has investigated MTX resistance. This study investigated the potential of natural chemicals, specifically nobiletin and sinensetin, to overcome MTX resistance in breast cancer cells using MTX-resistant MCF-7 (MCF-7/MTX) and MCF-7 cells. Protein targets of citrus flavonoids were identified from multiple databases and were collected using Venny 2.1. Microarray data of MCF-7 and MCF-7/MTX cells were acquired from the Gene Expression Omnibus. Subsequently, we constructed a protein-protein interaction network and selected the hub proteins. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, drug- and disease-gene enrichment analyses, genetic alteration examination, receiver operating characteristic curve analysis, mRNA levels analysis, prognostic value analysis, and molecular docking analysis were performed along with in vitro experiments. Cytotoxicity of citrus flavonoids (individually and combined) was assessed in MCF-7/MTX cells. Nobiletin and sinensetin significantly enhanced the cytotoxicity of MTX in MCF-7/MTX cells. BCL2L1, CDK1, EGFR, PTGS2, PLK1, MMP2, ACHE, ABCG2, and KIT genes were enriched in cholinesterase activity, cell cycle regulation, and the PI3K/Akt signaling pathway. Nobiletin and sinensetin impeded PLK1, CDK1, and ACHE activities based on molecular docking. Nobiletin and sinensetin in combination with MTX may overcome breast cancer cell resistance to MTX.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"365"},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel PAK1/TCF1 regulatory axis promotes non-small cell lung cancer progression.","authors":"Chuangang Lu, Yuncong Su, Youzhong Xu, Siyuan Sheng, Taiting Chen, Juan Li","doi":"10.1007/s12672-025-02110-4","DOIUrl":"10.1007/s12672-025-02110-4","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) is the leading cause of cancer death, necessitating the identification of novel therapeutic targets. P21-activated kinases-1 (PAK1) plays a crucial role in oncogenesis, including NSCLC. Recent findings have elucidated T cell factor 1 (TCF1) as an anti-tumour factor, influencing T cell biology. However, the precise mechanism by which PAK1 promotes NSCLC progression via TCF1 regulation remains unclear.</p><p><strong>Methods: </strong>We collected 23 pairs of NSCLC tissue samples and obtained NSCLC RNA sequencing data and corresponding clinicopathologic information from The Cancer Genome Atlas (TCGA). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) assessed PAK1 and TCF1 expression in NSCLC tissues and cells. Gain and loss-of-function experiments evaluated PAK1 and TCF1 effects on cell proliferation, invasion, migration, and apoptosis in vitro. Mechanistically, western blot (WB) and immunoprecipitation analysis evaluated the interaction between PAK1 and TCF1 in NSCLC. Finally, we assessed the clinical prognostic, disease progression, and immunotherapy response of PAK1 and TCF1 and their correlation with immune cell infiltration, immune checkpoint inhibitors (PD1, PDL1).</p><p><strong>Results: </strong>PAK1 expression was elevated in NSCLC tissues and cells, while TCF1 was significantly downregulated. PAK1 expression showed a significant inverse correlation with TCF1 mRNA in NSCLC. Silencing PAK1 (using shRNAs) and inhibiting PAK1 with the small molecule IPA-3 suppressed NSCLC cell malignancy in a dose-dependent manner, upregulating TCF1 expression, and vice versa. TCF1 amplification with the small molecule (TWS119) inhibited NSCLC cell proliferation, migration, and invasion in a dose-dependent manner without affecting PAK1 expression. Immunoprecipitation analysis confirmed PAK1 and TCF1 interaction in NSCLC. Joint survival analysis indicated that high PAK1 and low TCF1 expression were associated with unfavourable survival in patients with NSCLC. Lastly, the TCF1 was significantly correlated with immune cell infiltration [CD8+ T cell, and tumor infiltrating lymphocytes (TILs)], immune checkpoint inhibitors (PD1, PDL1), and can accurately predict the immunotherapeutic response.</p><p><strong>Conclusion: </strong>This study demonstrates, for the first time, that PAK1 negatively regulates TCF1, contributing to NSCLC pathogenesis. The PAK1/TCF1 regulatory axis emerges as a critical determinant of carcinogenesis and a promising therapeutic target for NSCLC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"364"},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analyzing research trends in the relationship between immunosuppressants and cancer following organ transplantation: a bibliometric study from 2001 to 2023.","authors":"Xing Liu, Ren-Chun Du, Jing-Yuan Xu, Yu-Xin Hu, Xun Xie, Qing-Yang Lan, Liaoliao Hu","doi":"10.1007/s12672-025-02101-5","DOIUrl":"10.1007/s12672-025-02101-5","url":null,"abstract":"<p><strong>Background: </strong>Recently, there has been an increasing interest in investigating the potential benefits or risks associated with using immunosuppressants for treating specific tumors post organ transplantation, with a focus on selecting appropriate drugs, doses, and treatment protocols. This study used bibliometric analysis to evaluate research trends and hotspots in this field.</p><p><strong>Materials and methods: </strong>A systematic search was conducted on the Web of Science to identify studies focusing immunosuppressants and cancer following organ transplantation from 2001 to 2023. The search strategy utilized a variety of the keywords including \"immunosuppressants\", \"cancer\" and \"transplant\". Data extraction involved recording various parameters such as title, author, institution, country, publication, citation, H-index, immunosuppressant, and type of transplantation.</p><p><strong>Results: </strong>The analysis encompassed a total of 94 studies. The findings revealed that the period from 2005 to 2010 emerged as the most influential timeframe within this research. The United States ranked highest in the number of publications, with Vivarelli M identified as the most productive author, and the University of Bologna recognized as the most productive institute. \"Immunosuppression\", \"rapamycin\" and \"kidney\" were identified as the key hotspots within this field. Notably, rapamycin was identified as the predominant immunosuppressant and kidney transplantation emerged as the most prominent type of transplantation.</p><p><strong>Conclusions: </strong>While immunosuppressants have been extensively utilized in organ transplant procedures, certain associated cancer risks have not been well addressed. Further long-term monitoring studies are required for numerous immunosuppressants to elucidate precise applications and potential implications for solid-organ transplant recipients.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"366"},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression and prognosis of NR3C1 in uterine corpus endometrial carcinoma based on multiple datasets.","authors":"Yahui Shen, Peihan Yang, Yanping Lu","doi":"10.1007/s12672-025-02086-1","DOIUrl":"10.1007/s12672-025-02086-1","url":null,"abstract":"<p><p>Uterine corpus endometrial carcinoma (UCEC), a prevalent malignancy in the female reproductive system, has witnessed a 30% increase in recent year. Recognizing the significance of early treatment in reducing patient mortality, the identification of potential biomarkers for UCEC plays a crucial role in early diagnosis. This study was to identify key genes associated with UCEC utilizing the Gene Expression Omnibus database, followed by validating their prognostic value across multiple databases. Analysis of four UCEC databases (GSE17025, GSE36389, GSE63678, GSE115810) yielded 72 co-expressed genes. KEGG and GO enrichment analyses revealed their involvement in physiological processes such as transcriptional misregulation in cancer. Constructing a protein-protein interaction network for these 72 genes, the top 10 genes with significant interactions were identified. Survival regression analysis highlighted NR3C1 as the gene with a substantial impact on UCEC prognostic outcomes. Differential expression analysis indicated lower expression of NR3C1 in UCEC compared to normal endometrial tissue. Cox regression analysis, performed on clinical datasets of UCEC patients, identified clinical stage III, clinical stage IV, age, and NR3C1 as independent prognostic factors influencing UCEC outcomes. The LinkedOmics online database revealed the top 50 positively and negatively correlated genes with NR3C1 in UCEC. Subsequent investigations into the relationship between NR3C1 and tumor-infiltrating immune cells were conducted using R software. Gene set enrichment analysis provided insights into NR3C1-related genes, showing enrichment in processes such as Ribosome, Oxidative phosphorylation in UCEC. Collectively, these comprehensive analyses suggest that NR3C1 may serve as a potential biomarker indicating the prognosis of UCEC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"370"},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Classification of lung adenocarcinoma based on senescence-related genes identifies a cluster with immunotherapy resistance and poor prognosis.","authors":"Xinrui Gao, Xiang Shen, Shasha Huang, Shangke Huang","doi":"10.1007/s12672-025-02127-9","DOIUrl":"10.1007/s12672-025-02127-9","url":null,"abstract":"<p><p>Lung adenocarcinoma is one of the major contributors to cancer-related mortality, with immunotherapy emerging as a key treatment. However, many patients exhibit resistance to immune checkpoint inhibitors. Cellular senescence has been linked to tumor progression and drug resistance, influencing the tumor microenvironment. This study applied consensus clustering to classify lung adenocarcinoma patients into two clusters based on senescence-related gene expression, revealing differing immune characteristics. One of the identified clusters exhibited immunosuppressive characteristics and showed resistance to immunotherapy. A senescence-related risk score was developed using machine learning to predict immunotherapy response and prognosis. High senescence-related risk score correlated with poorer survival and increased immunotherapy resistance across multiple cancer types. The senescence-related risk score model showed robust predictive ability in both the training and validation cohorts. These findings suggest a link between senescence and immunotherapy resistance, and further investigation into their relationship could reveal new perspectives for cancer treatment.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"363"},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatic analysis of serpina1 expression in papillary thyroid carcinoma and its potential association with Hashimoto's thyroiditis.","authors":"Xiuyuan Du, Wanjun Chen","doi":"10.1007/s12672-025-02079-0","DOIUrl":"10.1007/s12672-025-02079-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;Previous studies have suggested that SERPINA1 may promote a better prognosis in papillary thyroid carcinoma (PTC) along with Hashimoto's thyroiditis (HT). This study aims to further explore the role of the SERPINA1 gene in PTC and its relationship with HT using multiple databases.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Transcriptomic data from The Cancer Genome Atlas (TCGA) were utilized to analyze differences in SERPINA1 expression between PTC patients with and without HT. The expression levels of SERPINA1 in tumor tissues and its association with tumor characteristics were assessed using the Wilcoxon test across both patient groups. The impact of SERPINA1 expression on immune cell infiltration in PTC was evaluated using the CIBERSORT tool. Single-cell transcriptomic data from the Gene Expression Omnibus (GEO) were further analyzed to identify SERPINA1-expressing subpopulations based on Thyroid Differentiation Score (TDS) and pseudotime analysis. Gene Set Variation Analysis (GSVA) was employed to characterize pathways associated with SERPINA1, inferring its potential functions. Finally, CellChat was used to investigate key ligand-receptor interactions between SERPINA1-positive subpopulations and other cell types.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;TCGA data analysis reveals that, compared to normal thyroid tissue, the transcriptional level of SERPINA1 is significantly elevated in PTC tissues. Moreover, the expression of SERPINA1 is closely linked to certain clinical pathological features of PTC and the infiltration of immune cells in the tumor microenvironment. Single-cell transcriptome analysis reveals that SERPINA1 is primarily expressed in thyrocytes and myeloid cells. In thyrocytes, SERPINA1 is associated with complement-related proteins (e.g., C3, CD55). In poorly differentiated thyrocytes, it is linked to protease inhibitors and epithelial-mesenchymal transition (EMT) pathways, while in moderately differentiated thyrocytes, it associates with apolipoproteins APOE and APOC1. In macrophages, SERPINA1 is highly expressed in HT-associated macrophages and unpolarized macrophages, correlating with inflammation and extracellular matrix regulation pathways. Cell-cell interaction analysis indicates that SERPINA1-positive cells interact with other cells in the tumor microenvironment through macrophage migration inhibitory factor (MIF) and fibronectin 1 (FN1).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Compared to normal thyroid tissue or cells, the expression level of SERPINA1 is elevated in PTC. In cancer cells, SERPINA1 may be associated with the complement system and complement regulator functions. In poorly differentiated thyrocytes, SERPINA1 may primarily function as a protease inhibitor and is closely related to FN1. In moderately differentiated thyrocytes, SERPINA1 is associated with apolipoproteins. In unpolarized macrophages, the function of SERPINA1 may be to act as a serine protease inhibitor, participating in the remodeling of","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"356"},"PeriodicalIF":2.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}