Muhammad Alaa Eldeen, Abdelrahman Mostafa, Farag Mamdouh, Waleed K Abdulsahib, Dalal Sulaiman Alshaya, Eman Fayad, Hassan M Otifi, Hesham M Hassan, Mohammed Alshehri, Aiysha Althobaiti, Ghadi Alsharif, Mohamed A Soltan
{"title":"Correction: Oncogenic EME1 promotes tumor progression and immune modulation in human cancers with therapeutic targeting potential.","authors":"Muhammad Alaa Eldeen, Abdelrahman Mostafa, Farag Mamdouh, Waleed K Abdulsahib, Dalal Sulaiman Alshaya, Eman Fayad, Hassan M Otifi, Hesham M Hassan, Mohammed Alshehri, Aiysha Althobaiti, Ghadi Alsharif, Mohamed A Soltan","doi":"10.1007/s12672-025-03890-5","DOIUrl":"https://doi.org/10.1007/s12672-025-03890-5","url":null,"abstract":"","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1957"},"PeriodicalIF":2.9,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ilkbal Temel Yüksel, Gazi Güner, Neçirvan Çağdaş Çaltek, Semih Tek, Ayşe Hazırbulan, Gözde Şahin
{"title":"Evaluation of serum MUC5AC for identifying high grade cervical lesions in a prospective cohort from Türkiye.","authors":"Ilkbal Temel Yüksel, Gazi Güner, Neçirvan Çağdaş Çaltek, Semih Tek, Ayşe Hazırbulan, Gözde Şahin","doi":"10.1007/s12672-025-03870-9","DOIUrl":"https://doi.org/10.1007/s12672-025-03870-9","url":null,"abstract":"<p><strong>Background: </strong>Abnormal expression of mucins and changes in their glycosylation are linked to the onset and advancement of cancerous conditions. This research sought to assess the diagnostic significance of serum MUC5AC levels in differentiating between high-grade cervical intraepithelial lesions, low-grade lesions, and normal cervical findings, as well as to investigate its potential as a non-invasive biomarker to enhance cervical cancer screening and early detection methods.</p><p><strong>Methods: </strong>A total of 138 women were stratified into three groups: CIN 1 (LSIL) (n = 38), CIN 2-3 (HSIL) (n = 54), and controls (n = 46). Serum levels of MUC5AC were assessed through enzyme-linked immunosorbent assay (ELISA). All participants underwent cytological assessment, HPV testing, and colposcopy with targeted biopsy; endocervical curettage and LEEP were performed when indicated.</p><p><strong>Results: </strong>Serum MUC5AC levels were significantly higher in the CIN 2-3 group compared to both the control and CIN 1 groups (p = 0.016), while no significant difference was found between the control and CIN 1 groups. ROC analysis demonstrated that MUC5AC had moderate diagnostic performance in distinguishing CIN 2-3 from controls (AUC = 0.634, p = 0.022) and from CIN 1 (AUC = 0.658, p = 0.011), with high sensitivity but low specificity. No significant discriminative value was observed in the comparisons involving the CIN 1 and control groups.</p><p><strong>Conclusion: </strong>Serum MUC5AC exhibited significant sensitivity in detecting high-grade cervical lesions; however, its specificity was somewhat restricted. Although it may not serve as an adequate standalone marker for early lesions, it shows potential for identifying advanced pathology.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1958"},"PeriodicalIF":2.9,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Protein interacting with C-kinase 1 is correlated to prognosis and immune infiltrates of gastric cancer.","authors":"Ying Zhou, Biqin Zhang, Feng Li, Xiaohong Li, Yutao Zhang, Yaoqiang Du","doi":"10.1007/s12672-025-03783-7","DOIUrl":"https://doi.org/10.1007/s12672-025-03783-7","url":null,"abstract":"<p><strong>Background: </strong>Protein interacting with C-kinase 1 (PICK1) has been proved to be involved in many malignant tumors, such as neurological tumors, digestive system tumors and breast cancer. However, its biological role in tumor immune microenvironment of gastric cancer (GC) is still unclear.</p><p><strong>Methods: </strong>Public datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were acquired for the purpose of examining the relationship between the expression of PICK1 mRNA and clinical characteristics, as well as the survival of patients with GC. The utilization of CIBERSORT and TIMER web servers allowed for the exploration of the association between the expression level of PICK1 mRNA and the level of immune infiltrates in GC tissues. Additionally, the implementation of Gene Set Enrichment Analysis (GSEA) provided evidences for this connection. Finally, correlation analysis was conducted to assess the relationship between the expression of PICK1 mRNA and specific classical immune cell markers.</p><p><strong>Results: </strong>We discovered that decreased PICK1 mRNA expression in GC tissues indicated a poor TNM stage and shorter overall survival duration. In addition, expression level of PICK1 mRNA was demonstrated to be relevant to the relative levels of immune infiltrates in GC tissues, especially the macrophages. Furthermore, our findings demonstrated that PICK1 mRNA was adversely linked with M2 macrophage markers.</p><p><strong>Conclusion: </strong>The decreased PICK1 expression was believed to benefit the infiltration of macrophages and the polarization of M2 macrophages, and finally lead to an unfavorable prognosis for GC patients.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1950"},"PeriodicalIF":2.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhijun Chen, Han Guan, Long Chen, Xinwei Yuan, Wenyan Sun, Ming Chen
{"title":"Comprehensive pan-cancer evaluation of NUP85 prognosis, immune infiltration response, and validation in prostate cancer.","authors":"Zhijun Chen, Han Guan, Long Chen, Xinwei Yuan, Wenyan Sun, Ming Chen","doi":"10.1007/s12672-025-03735-1","DOIUrl":"https://doi.org/10.1007/s12672-025-03735-1","url":null,"abstract":"<p><strong>Background: </strong>Although NUP85 is a member of the nuclear pore complex (NPC) and is associated with chromosome variation and tumor regulation, its specific role in cancer development remains unclear and requires further research.</p><p><strong>Methods: </strong>This study analyzes the mRNA and protein levels of NUP85 in normal and tumor tissues using the TCGA, GTEx, and HPA databases. We investigated the relationship between NUP85 and survival rates, as well as clinical features, in various tumors by analyzing the TCGA database. The expression pattern of NUP85 in cancer cells is analyzed using single-cell sequencing data from the TISCH database. Two types of prostate cancer cell lines are utilized to investigate the impact of NUP85 on cell proliferation, migration, invasion, and apoptosis, as well as its regulatory mechanism. These analyses aim to uncover the role of NUP85 in cancer, particularly in prostate cancer.</p><p><strong>Results: </strong>NUP85 is observed to exhibit elevated expression levels across multiple malignancies, with its heightened expression showing consistent associations with poorer clinical prognoses. Bioinformatic analyses further reveal that NUP85 expression patterns demonstrate significant correlations with the activity of cancer-related pathways and immunological interactions involving macrophages and T cell populations. Notably, experimental studies using prostate cancer models have documented reduced cellular proliferation following NUP85 knockout, suggesting a potential functional connection warranting further mechanistic investigation.</p><p><strong>Conclusions: </strong>The results indicate that elevated NUP85 expression shows strong correlations with cancer initiation and progression. These findings support its potential utility as a candidate biomarker for disease monitoring across various malignancies, though mechanistic validation remains necessary to establish clinical applicability.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1953"},"PeriodicalIF":2.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Kaempferols from Echinacea purpurea demonstrate anti-cancer potential by targeting anexelekto in breast cancer therapy using chemoinformatics approach.","authors":"Saviour God'swealth Usin, Daniel Ogbonnaya Nwankwo, Anas Haruna Ruggah, Adebesin Ayomide Oluwadarasimi, Md Ahad Ali, Timothy Oluwatimileyin Ayeni, Abass Abdulateef Ohilebo, Abdulsamad Omotayo Aiyelabegan, Opeyemi Christianah De Campos, Kayode Raheem Yomi, Siham Lakrikh, Awotunde Oluwasegun Samson, Cornelius Ayodeji Aboderin, Bodun Damilola Samuel, Abdulwasiu Ibrahim, Toheeb Adewale Balogun","doi":"10.1007/s12672-025-03541-9","DOIUrl":"https://doi.org/10.1007/s12672-025-03541-9","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is one of the most common cancer types among women, especially in developing and underdeveloped nations like Nigeria. Anexelekto (AXL) is one of the well-known proteins that is implicated in various cancer types, including breast cancer, and it remains one of the focuses of targeted therapy. However, several drugs have been identified as inhibitors of this oncogenic protein, but they often come with toxic concerns in addition to their unaffordability to people of low- or middle-income countries. Thus, there is a crucial need to identify pocket-friendly inhibitors with negligible side effects targeting AXL. Therefore, bioactive compounds from plants such as Echinacea purpurea may be a promising agent in this regard.</p><p><strong>Objective: </strong>The study sought to investigate the potential of bioactive compounds derived from Echinacea purpurea to inhibit the AXL protein implicated in breast cancer.</p><p><strong>Methods: </strong>Structural bioinformatics via molecular docking and density functional theory (DFT) analysis was utilised for the identification of novel AXL inhibitors from Echinacea purpurea bioactive compounds. The compounds were further subjected to pharmacokinetic and drug-likeness analysis. Results obtained from the compounds were compared against those of Foretinib, a known AXL inhibitor. Additionally, their complexes with AXL were subjected to a 100 ns molecular dynamics (MD) simulation analysis utilising the Desmond v2020-4 software in Schrödinger (Academic version) in a Linux environment.</p><p><strong>Results: </strong>Among all favourable binding scores, Kaempferol-7-o-Neohesperidoside, Kaempferol 3-gentiobioside-7-rhamnoside, and Kaempferol 3-o-beta-d-glucopyranosyl-7-o-alpha-L-rhamnopyranoside showed the highest binding score of -9.2, -8.9, and - 8.6 Kcal/mol, respectively, compared to Foretinib (-8.1 Kcal/mol). Stigmasterol and β-sitosterol also showed a higher binding affinity and binding score of -8.4 and - 8.3 Kcal/mol, respectively, against the AXL compared to the standard drug. DFT analysis revealed that Kaempferol 3-o-beta-d-glucopyranosyl-7-o-alpha-L-rhamnopyranoside has the highest LUMO-HOMO gap of -4.354 eV, suggesting greater potential for electron donation and high drug-enzyme reactivity. Also, the pharmacokinetic profiling of the selected compounds is favourable. Findings from MD simulation showed that the protein-ligand complexes formed by these compounds maintained structural stability, compactness, and low atomic fluctuations throughout a 100-ns simulation period.</p><p><strong>Conclusion: </strong>In silico studies show that E. purpurea-derived compounds, especially Kaempferol 3-o-beta-d-glucopyranosyl-7-o-alpha-L-rhamnopyranoside, have better inhibitory potential against AXL and better pharmacokinetic profiles when compared with Foretinib. These compounds are thus proposed as novel AXL inhibitors for the treatment of breast cancer. Further, in vivo studies","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1954"},"PeriodicalIF":2.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prognostic significance of GPR132 in papillary thyroid carcinoma: insights from integrated machine learning and its role in regulating TPC-1 cell growth.","authors":"Jinghua Gao, Zihan Cai, Shoupeng Ding, Lanxin Ma, Jian Han, Yi-Yi Luo, Xueli Yang, Liqin Zhou, Wen Mei, Xiangfang Li, Lin Meng, Heng Luo","doi":"10.1007/s12672-025-03833-0","DOIUrl":"https://doi.org/10.1007/s12672-025-03833-0","url":null,"abstract":"<p><strong>Object: </strong>This study utilizes machine learning and bioinformatics methods to analyze data identifying GPR132 as a reliable potential prognostic gene for papillary thyroid carcinoma (PTC).The experiments elucidated potential role of GPR132 in inhibiting tumor growth in PTC by regulating the cell cycle and apoptotic mechanisms. This research provides significant insights for future personalized therapeutic strategies aimed at targeting PTC.</p><p><strong>Methods: </strong>The study analyzed the GSE191288 RNA-seq dataset, which included six thyroid cancer tumor samples and one adjacent normal tissue sample, to identify genes associated with tumor-associated macrophages (TAMs). After conducting a thorough enrichment analysis, we used the CellChat tool to investigate the signaling pathways.Pseudotemporal analysis elucidated the differentiation status of TAMs, and weighted gene co-expression network analysis(WGCNA) identified M1-like TAM-related genes within the M1 macrophage module. Integration with the GEO database revealed that GPR132 is a key prognostic gene. The effects of GPR132 overexpression on the proliferation, migration, apoptosis, and cell cycle progression of thyroid papillary carcinoma (TPC-1) cells were evaluated through cell-based experiments.</p><p><strong>Results: </strong>Single-cell sequencing revealed 20 distinct cell clusters, categorized as epithelial, stromal, or immune cells, with a focus on TAMs.Enrichment analysis associated TAM-expressed genes with immune response regulation. Pseudotime analysis identified TAMs differentiation states, while WGCNA linked a low abundance of M1 macrophages to favorable PTC prognosis. Integration with the GEO database confirmed GPR132 as a key prognostic gene. Cellular experiments showed that GPR132 overexpression markedly inhibited TPC-1 cell proliferation and migration, likely through G1 phase cell cycle arrest and enhanced apoptosis. Flow cytometry confirmed elevated early and total apoptosis rates in GPR132-overexpressing cells.</p><p><strong>Conclusion: </strong>GPR132 was identified as a critical prognostic gene for PTC, with evidence suggesting its role in tumor suppression via cell cycle modulation and apoptosis induction.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1956"},"PeriodicalIF":2.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Peripheral SNCA<sup>+</sup> cells as a poor prognostic factor for nivolumab therapy in advanced gastric cancer.","authors":"Chie Kudo-Saito, Hiroshi Imazeki, Kengo Nagashima, Hirokazu Shoji, Kai Tsugaru, Naoki Takahashi, Takeshi Kawakami, Yusuke Amanuma, Takeru Wakatsuki, Naohiro Okano, Yukiya Narita, Yoshiyuki Yamamoto, Rika Kizawa, Kei Muro, Narikazu Boku","doi":"10.1007/s12672-025-03817-0","DOIUrl":"https://doi.org/10.1007/s12672-025-03817-0","url":null,"abstract":"<p><strong>Background: </strong>We previously demonstrated that immune cells expressing α-synuclein (SNCA) are dramatically increased in peripheral blood of patients with gastric cancer (GC), but rarely in healthy donors, and that blocking SNCA is significantly effective even in anti-PD1-resistant mouse tumor models with increased SNCA<sup>+</sup> cells. This suggests that the increased SNCA<sup>+</sup> cells are involved in resistance to anti-PD1 therapy. However, the relationship between SNCA<sup>+</sup> cell levels and anti-PD1/PDL1 therapeutic efficacy in GC remains to be determined in clinical settings.</p><p><strong>Methods: </strong>In the WJOG10417GTR study, peripheral blood cells collected from advanced GC patients before and one month after nivolumab monotherapy were analyzed for several SNCA<sup>+</sup> cell populations by flow cytometry, and the relationship between the levels and patient prognosis was statistically analyzed.</p><p><strong>Results: </strong>High levels of SNCA<sup>+</sup> cells, particularly the myeloid subset, before and after treatment were significantly associated with shorter progression-free survival and overall survival. Patients with low SNCA<sup>+</sup> cell levels survived for a long time without disease progression, indicating durable responders.</p><p><strong>Conclusion: </strong>These suggest that SNCA<sup>+</sup> cells are significant poor prognostic factors in nivolumab therapy for advanced GC. Targeting SNCA may be a promising strategy to improve clinical outcomes in anti-PD1/PDL1 therapy for GC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1951"},"PeriodicalIF":2.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CER1 as a manganese ion metabolism gene drives gastric cancer progression and therapeutic potential via oxidative stress and tumor microenvironment regulation.","authors":"Juan Hu, Ruian Zhu, Qiushi Huang, Xiaosong Li","doi":"10.1007/s12672-025-03502-2","DOIUrl":"https://doi.org/10.1007/s12672-025-03502-2","url":null,"abstract":"<p><strong>Background: </strong>Metal ions are vital for biological regulation and contribute to gastric cancer (GC) development, but the mechanisms are unclear. This study investigates the role of the manganese ion metabolism (MIM)-related gene CER1 in GC, focusing on how CER1 induces oxidative stress, contributes to tumor microenvironment heterogeneity, and its potential for targeted personalized therapy.</p><p><strong>Methods: </strong>Using single-cell RNA sequencing and multi-omics technologies, we characterized molecular subtypes of gastric cancer (GC) and explored the biological roles of the MIM family, elucidating genetic mechanisms of GC initiation and immune dysregulation.</p><p><strong>Results: </strong>Our analysis systematically clarified the pivotal role of the MIM gene family in GC, and revealed that CER1 promoted T cell exhaustion and facilitated immune evasion. The bioinformatics analysis indicated that CER1 may regulate tumor cell biological behavior through the NRF2/KEAP1-mediated oxidative stress signaling pathway. In summary, CER1, as a member of the MIM family, serves as a central hub in the oxidative stress and immune regulation.</p><p><strong>Conclusion: </strong>The in-depth investigation of CER1 within the MIM family has markedly deepened our understanding of the complex molecular mechanisms underlying GC. Through targeted manipulation of the NRF2/KEAP1 oxidative stress pathway and T cell function, CER1 emerges as a strategic pathway for potentially inhibiting tumor growth. This investigation outlines a strategic framework to facilitate the advancement of innovative treatment modalities.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1955"},"PeriodicalIF":2.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}