Oncology reports最新文献

{"title":"T cell exhaustion‑related gene CD79B predicts prognosis, inhibits malignant progression and promotes tumor‑associated macrophage M1‑like polarization in lung adenocarcinoma.","authors":"Xia Wu, Chunhui Qu, Yiting Ouyang, Lifang Yang, Wuzhong Jiang","doi":"10.3892/or.2025.8977","DOIUrl":"10.3892/or.2025.8977","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) is one of the most common malignancies in the lung. T cell exhaustion (TEX) is an important immune escape mechanism that may be targeted to improve tumor immunotherapy. The present study investigated TEX‑related genes in the tumor microenvironment to predict the prognosis of patients with LUAD. Data from 516 patients with LUAD were collected from The Cancer Genome Atlas database and classified them into TEX‑C1 and TEX‑C2 by unsupervised clustering based on the TEX‑related genes. Compared with TEX‑C1, TEX‑C2 cluster had worse prognosis, with shorter overall and progression‑free survival. Functional analysis revealed that upregulated genes in the TEX‑C2 cluster were significantly enriched in tumor immune‑ and metabolism‑related pathways. TEX‑C2 cluster had a poor immune checkpoint blockade (ICB) response and a shorter survival after ICB treatment by Tumor Immune Dysfunction and Exclusion algorithm. A prognostic TEX‑related gene signature was constructed for patients with LUAD by Least Absolute Shrinkage and Selection Operator regression analysis. B cell antigen receptor complex‑associated protein β chain (CD79B) was considered an independent prognostic indicator; in the clinical correlation analysis, the effect of CD79B on prognosis was associated with advanced lung cancer, advanced age, female sex and patients with history of smoking. The overexpression of CD79B was associated with more infiltration of CD8⁺ T cells, M1 macrophages (the classically activated type 1, pro‑inflammatory type), and less infiltration of M0 (undifferentiated) and M2 macrophages (the alternatively activated type 2, anti‑inflammatory type) by CIBERSORT algorithm, which was also significantly correlated with gene markers of innate and adaptive immune cells, and higher levels of immune checkpoint genes. Upregulation of CD79B could inhibit the proliferation, migration and invasion capabilities and promote the apoptosis of LUAD cells, and induce M1‑like tumor‑associated macrophage (TAM) polarization. In conclusion, patients with LUAD in the TEX‑C2 cluster had worse prognosis and adverse immune microenvironment. CD79B may be a potential prognostic indicator, which could inhibit malignant progression of LUAD cells and induce M1‑like TAM polarization.</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":"54 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12402755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of autophagy‑modulating long non‑coding RNAs in tumor radioresistance (Review).","authors":"Hailong Li, Zhengxi He","doi":"10.3892/or.2025.8975","DOIUrl":"10.3892/or.2025.8975","url":null,"abstract":"<p><p>Radiotherapy improves survival rates in patients with cancer; however, the development of radioresistance hinders its effectiveness, resulting in unfavorable outcomes. A key factor in cancer progression is the dysregulation of autophagy, a lysosomal degradation process governed by various evolutionarily conserved autophagy‑related genes (ATGs). Long non‑coding RNAs (lncRNAs) serve a crucial role in the regulation of autophagy. lncRNAs modulate ATGs and their signaling pathways, contributing to the emergence of radioresistance. The present review offers a comprehensive examination of the critical roles of autophagy and lncRNAs in mediating radioresistance. By enhancing the understanding of these mechanisms, novel therapeutic strategies aimed at increasing tumor radiosensitivity through the modulation of autophagy may be revealed.</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":"54 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12402759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Irradiation‑induced cellular senescence is linked to pro‑survival signaling and checkpoint regulation in a 2D and 3D model for head and neck cancer.","authors":"Luis Bugia, Annette Affolter, Johann Kern, Emma Sohn, Frederic Jungbauer, Jens Fleckenstein, Anne Lammert, Nicole Rotter, Claudia Scherl","doi":"10.3892/or.2025.8984","DOIUrl":"10.3892/or.2025.8984","url":null,"abstract":"<p><p>Fractionated irradiation causes premature senescence of tumor cells. Interactions between senescence, the immune system and survival signaling are poorly understood to date. As MAP kinases are implicated in immune resistance, the present study addressed the detection of senescence‑associated modulation of postradiogenic programmed death‑ligand 1 (PD‑L1) and MAP kinase ERK1/2 expression in an <i>in vitro</i> and <i>ex vivo</i> model for head and neck squamous cell carcinoma (HNSCC). Established HNSCC cell  lines (UM-SCC-11B, UM-SCC-14C and UM-SCC-22B) were employed to study the expression levels of p21, histone  H2AX (γH2AX), PD-L1 and phosphorylated (p)ERK1/2 via immunohistochemistry following application of 4x2 Gy. Using senescence‑associated β‑galactosidase (SA‑ß‑Gal) staining, postradiogenic induction of senescence was additionally assessed. Results were validated in a 3D <i>ex vivo</i> HNSCC model with vital explants. Upon ionizing radiation (IR), senescence‑like subpopulations were observed in all cell lines, showing upregulation of PD‑L1 and pERK1/2 as well as of established senescence markers p21 and γH2AX. SA‑β‑Gal‑positive cells were found in all lines. These results were supported in a 3D tumor model. Fractionated IR can generate a subpopulation of HNSCC cells characterized by senescence‑typical cellular changes and marked expression of PD‑L1 and pERK1/2. Postradiogenic senescence in both 2D and 3D cancer models was possibly related to survival signaling and immune checkpoint regulation, crucial elements in tumor development and progress.</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":"54 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Senescence‑associated IL‑33 secretion undermines sorafenib efficacy in hepatocellular carcinoma via immune evasion.","authors":"Yu-Xin Lin, Hsien Liu, Wei-Chiao Liao, Yi-Ching Wang, Bo-Cheng Zhang, Shu-Wen Wan, Chien-Chin Chen, Chih-Peng Chang","doi":"10.3892/or.2025.8987","DOIUrl":"10.3892/or.2025.8987","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a highly lethal cancer with increasing incidence rates worldwide. The recommended treatments for advanced‑stage HCC are sorafenib and regorafenib; however, developing resistance to these medications significantly limits their effectiveness, and the underlying mechanisms are poorly understood. The present study demonstrated that interleukin‑33 (IL‑33) promotes sorafenib resistance via immune regulation. <i>In vitro</i>, western blotting and reverse transcription‑quantitative PCR showed that both sorafenib and regorafenib treatments led to an increase in the upregulation and secretion of IL‑33 through a positive feedback loop involving the IL‑33/transmembrane suppression of tumorigenicity 2 (ST2L) pathway. Senescence‑associated β‑galactosidase staining and western blotting revealed that sorafenib and regorafenib treatments induce cell senescence in HCC cells. Flow cytometric analysis indicated that he secreted IL‑33 enhanced programmed cell death ligand 1 (PD‑L1) expression in HCC cells by activating NF‑κB pathways in response to the treatments. <i>In vivo</i>, a HCC‑bearing subcutaneous mouse model revealed that blocking the IL‑33 signaling pathway with anti‑IL‑33 or anti‑ST2L neutralizing antibodies, combined with sorafenib, significantly reduced tumor size, growth rate, and weight. Additionally, there was a notable decrease in tumor PD‑L1 expression and an increase in intra‑tumor CD8⁺ T cells infiltration. Importantly, the enhanced therapeutic efficacy of the anti‑IL‑33 treatment in sorafenib‑treated HCC‑bearing mice was lost in immunocompromised mice. This indicates that the anti‑IL‑33 neutralizing antibody enhances the antitumor activity of sorafenib by modulating the immune response rather than directly affecting HCC cell proliferation. The findings of the present study suggested that IL‑33 plays a role in decreasing the therapeutic effectiveness of sorafenib and regorafenib in HCC cells. The present study highlights the potential of targeting the IL‑33/ST2L axis in combination with targeted therapies as a novel strategy to improve the limited efficacy of sorafenib and regorafenib.</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":"54 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel tetravalent bispecific antibody, PSMA/TRAIL‑R2 REGULGENT™, induces selective tumor cell apoptosis without hepatotoxicity.","authors":"Makoto Nakayama, Sayaka Takagi-Maeda, Yusuke Machino, Kaito Nihira, Miho Inoue, Nobuaki Takahashi, Katsuaki Usami","doi":"10.3892/or.2025.8988","DOIUrl":"10.3892/or.2025.8988","url":null,"abstract":"<p><p>Tumor necrosis factor‑related apoptosis‑inducing ligand‑receptor 2 (TRAIL‑R2) can induce apoptosis in various tumors through the oligomerization of TRAIL. Several TRAIL‑R2 agonistic monoclonal antibodies have been tested in clinical trials but have failed owing to a lack of efficacy or severe hepatotoxicity. Although bispecific constructs have been developed to improve TRAIL‑R2 targeting and enhance efficacy against tumors while reducing adverse effects on hepatocytes, the risk of hepatotoxicity still persists. The present study used a TRAIL‑R2 antibody, E11, that does not trigger apoptosis in the absence of crosslinking and constructed a novel tetravalent bispecific IgG4‑based antibody, REGULGENT™, comprised of E11 and a clone that binds to prostate‑specific membrane antigen (PSMA), a specific marker for prostate tumors. PSMA/TRAIL‑R2 REGULGENT™ selectively induced death in PSMA/TRAIL‑R2 double‑positive cells but not in TRAIL‑R2 single‑positive cells <i>in vitro</i> and <i>in vivo</i>. By contrast, a bivalent bispecific antibody did not result in tumor cell death, indicating that tetravalent bispecific antibodies have an important role in inducing tumor cell apoptosis by binding to TRAIL‑R2 in a bivalent manner. Moreover, the present study demonstrated, for the first time to the best of the authors' knowledge, that PSMA/TRAIL‑R2 REGULGENT™ is not hepatotoxic <i>in vitro</i> (primary human hepatocytes) or <i>in vivo</i> (chimeric human hepatocyte‑transplanted PXB mouse model). This finding suggests that tetravalent bispecific therapeutics such as REGULGENT™ can be promising therapeutic agents for TRAIL‑R2‑positive tumors by exerting tumor‑specific activity while avoiding toxicity.</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":"54 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum from patients with oral squamous cell carcinoma remodels the tumor immune escape ecological niche by promoting regulatory T‑cell differentiation and T‑cell exhaustion.","authors":"Hongli Chen, Jiao Chen, Bomiao Cui, Die Lv, Wenwen Han, Yun Feng, Ping Zhang","doi":"10.3892/or.2025.8978","DOIUrl":"10.3892/or.2025.8978","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) ranks as the sixth most prevalent malignancy worldwide, and is characterized by high morbidity and mortality rates. Elucidating the molecular and cellular mechanisms of tumor‑directed immune escape through ecological niche remodeling is crucial for advancing tumor biotherapy. The serum of patients with cancer contains not only tumor biomarkers but also immune regulators secreted by immune cells and/or cancer cells. Notably, the interstitial fluid within the cancer ecological niche is derived from serum. The cross‑talk between serum and cancer cells determines the future of cancer cells, either cell survival or death. The present study revealed that serum from patients with OSCC could remodel the cancer immune escape ecological niche by promoting antigen‑induced regulatory T‑cell (Treg) differentiation and T‑cell exhaustion. When serum from patients with OSCC was added to a phytohemagglutinin‑stimulated peripheral blood mononuclear cell (PBMC) culture system, the Treg subset was significantly increased compared with that in the culture system treated with fetal bovine serum. Moreover, when the serum of patients with OSCC was added to a PBMC culture system stimulated with tumor antigens, the activation of the CD3⁺ subset was significantly inhibited, and high levels of IL‑4, IL‑10 and TGF‑β were detected in the supernatant; moreover, CD3⁺ T cells expressed high levels of T‑cell immunoglobulin and mucin‑domain containing‑3 and programmed death ligand 1, which is known to induce T‑cell apoptosis and exhaustion. Finally, the antitumor effect of T cells were significantly decreased. These results indicated that the serum of patients with cancer can promote the inhibition and exhaustion of antitumor T cells, thereby remodeling the tumor immune escape ecological niche.</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":"54 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12402752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Expression of Concern] miR‑30a inhibits glioma progression and stem cell‑like properties by repression of Wnt5a.","authors":"Yonghong Zhang, Zhi Wu, Lichao Li, Min Xie","doi":"10.3892/or.2025.8983","DOIUrl":"10.3892/or.2025.8983","url":null,"abstract":"<p><p>Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the control GADPH western blots shown in Fig. 5D were strikingly simillar to three lanes in the GAPDH panel shown in Fig. 4D, even though the experimental conditions reported in these figure parts were different, suggesting that one of these figures may have been assembled incorrectly. The authors were contacted by the Editorial Office to offer an explanation for this apparent anomaly in the presentation of the data in this paper; however, up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [Oncology Reports 38: 1156‑1162, 2017; DOI: 10.3892/or.2017.5728].</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":"54 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12426694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changing landscape of advanced esophageal squamous cell carcinoma: Breakthroughs in systemic therapies (Review).","authors":"Yueyue Li, Jingjing Li, Wenhui Mo, Xuanfu Xu","doi":"10.3892/or.2025.8953","DOIUrl":"10.3892/or.2025.8953","url":null,"abstract":"<p><p>The treatment of advanced esophageal squamous cell carcinoma (ESCC) presents numerous challenges. Whereas conventional therapies such as chemotherapy, radiotherapy and targeted treatments have achieved some success. However, the substantial heterogeneity of the disease poses challenges in achieving comprehensive therapeutic coverage through a single treatment approach, because molecular subtyping remains insufficiently defined. Consequently, the response rate to targeted therapies is limited. Moreover, the issue of resistance to immunotherapy is becoming increasingly prominent, and reliable predictive biomarkers are lacking. Additionally, the regulatory mechanisms of the tumor microenvironment in metastatic lesions require further investigation. In recent years, the advent of immunotherapy and novel drug development has brought new hope, particularly with the clinical application of antibody‑drug conjugates, bispecific antibodies, novel immune checkpoint inhibitors, new targeted therapies, and cell and vaccine therapies, which have markedly improved patient survival. The present review summarizes the current therapeutic landscape for advanced ESCC and discusses the potential of future treatment strategies. Despite improvements in survival rates with existing treatments, the integration of emerging therapies with precision medicine may become key to future ESCC management, through driving personalized treatment approaches and multidisciplinary collaboration, and ultimately improving patient quality of life and clinical outcomes.</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":"54 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive genetic profiling using tissue and blood in locally advanced tumors.","authors":"Kenji Fujiyoshi, Rie Sugihara, Naoki Miyamoto, Yoriko Watanabe, Tomoya Sudo, Sanae Numata, Jun Akiba, Hideyuki Abe, Yuka Ichinose, Kenji Inoue, Shuichi Ozono, Takeharu Ono, Kentaro Orioka, Masaki Kashihara, Ryousuke Kajiwara, Hiroyuki Kawano, Akihiko Kawahara, Ryuta Takase, Uhi Toh, Kazuaki Hashimoto, Toru Hisaka, Shingo Hirai, Masahiro Mitsuoka, Daiki Miyazaki, Fumi Yoshitomi, Ken Yamamoto, Hirohito Umeno, Masahisa Nomura, Yoshiki Naito","doi":"10.3892/or.2025.8967","DOIUrl":"10.3892/or.2025.8967","url":null,"abstract":"<p><p>Comprehensive genomic profiling (CGP) aims to assist clinicians with the diagnosis, treatment decisions and early detection of recurrence in patients with cancer. CGP using tumor tissue is widely implemented, whereas circulating tumor DNA (ctDNA) analysis is a noninvasive method that uses peripheral blood. This pilot study included eight patients with locally advanced tumors (two each of breast, lung, pancreatic, and head and neck cancers). The concordance of somatic variants with tumor tissues and paired ctDNA from pre‑ and post‑resection samples was evaluated. This study demonstrated that the overall concordance rate in all genes between tissue and postoperative blood was high (94.2%), but the concordance rate in genes with somatic variants was low (4.76%). In patient 8 with head and neck cancer, the <i>MAP2K1</i> variant was concordant between the tissue and blood after surgery. The patient was found to have a small lung tumor at 10 months after surgery, indicating recurrence in the lung. In patient 6 with pancreas cancer, the <i>TP53</i> variant was concordant between the blood before and after surgery, but no recurrence was observed. In patient 5 with pancreas cancer, recurrence was identified; however, the somatic variants were not concordant between the tissue and blood. Furthermore, a case, such as patient 8, of recurrence with somatic variants matching the tissue and postoperative blood was encountered, suggesting that detecting a somatic variant in postoperative ctDNA matching the same variant in the tissue may predict recurrence. However, since the major limitation of this study was the limited sample size, subsequent studies with larger sample sizes and more extensive research designs are warranted. The study was entered in the Japan Registry of Clinical Trials (April 10, 2023; no. 072230003).</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":"54 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High expression of eIF4A1 promotes angiogenesis through the NF‑κB/VEGFA pathway and predicts poor prognosis in gastric cancer.","authors":"Xiaoqun Zhu, Lizhou Jia, Xingwang Kuai, Qi Tang, Xinxia Chang, Xiao Zhang, Bing Chen, Hui Zhi, Haoran Hu, Xiaomei Huang, Zhenqing Feng, Wenbin Huang","doi":"10.3892/or.2025.8951","DOIUrl":"10.3892/or.2025.8951","url":null,"abstract":"<p><p>Increased eukaryotic translation initiation factor 4A (eIF4A1) expression is observed in numerous types of cancer and is associated with carcinogenesis; however, little is known about the role of eIF4A1 in gastric cancer (GC) angiogenesis. In the present study, a total of 1,758 gastric mucosa samples were collected for immunohistochemical staining in tissue microarrays. The expression levels of eIF4A1 and their association with clinicopathological characteristics and prognosis were analyzed using χ² test and univariate/multivariate analysis. The effects of abnormal eIF4A1 expression in GC cells on proangiogenic activity was detected using the Cell Counting Kit‑8 proliferation assay, wound healing assay, Transwell assay, angiogenesis assay and a subcutaneous tumor model. The role of eIF4A1 in tumor‑infiltrating lymphocytes was explored using bioinformatics analysis. Furthermore, the effect of eIF4A1 on proangiogenic factors was confirmed by the quantitative polymerase chain reaction and western blotting. Notably, eIF4A1 was highly expressed in GC tissues, and was associated with patient age, tumor differentiation, depth of invasion, distant metastasis and Tumor‑Node‑Metastasis stage. Furthermore, it was suggested that high eIF4A1 expression could be regarded as a poor prognostic biomarker for patients with GC. The expression levels of eIF4A1 in GC cells were also positively related to proliferation, migration and the tube formation of human umbilical vein endothelial cells, and microvessel density <i>in vivo</i>. Furthermore, eIF4A1 in GC cells regulated the infiltration of immune cells in the tumor microenvironment, and promoted the expression of VEGFA and NF‑κB. In conclusion, eIF4A1 may promote GC angiogenesis through the NF‑κB/VEGFA pathway, and could be considered an independent prognostic biomarker for patients with GC.</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":"54 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}