1161. StereoMM: a graph fusion model for integrating spatial transcriptomic data and pathological images.
作者: Bingying Luo.;Fei Teng.;Guo Tang.;Weixuan Cen.;Xing Liu.;Jinmiao Chen.;Chi Qu.;Xuanzhu Liu.;Xin Liu.;Wenyan Jiang.;Huaqiang Huang.;Yu Feng.;Xue Zhang.;Min Jian.;Mei Li.;Feng Xi.;Guibo Li.;Sha Liao.;Ao Chen.;Weimiao Yu.;Xun Xu.;Jiajun Zhang.
来源: Brief Bioinform. 2025年26卷3期
Spatial omics technologies, generating high-throughput and multimodal data, have necessitated the development of advanced data integration methods to facilitate comprehensive biological and clinical treatment discoveries. Based on the cross-attention concept, we developed an AI learning based toolchain called StereoMM, a graph based fusion model that can incorporate omics data such as gene expression, histological images, and spatial location. StereoMM uses an attention module for omics data interaction and a graph autoencoder to integrate spatial positions and omics data in a self-supervised manner. Applying StereoMM across various cancer types and platforms has demonstrated its robust capability. StereoMM outperforms competitors in identifying spatial regions reflecting tumour progression and shows promise in classifying colorectal cancer patients into deficient mismatch repair and proficient mismatch repair groups. The comprehensive inter-modal integration and efficiency of StereoMM enable researchers to construct spatial views of integrated multimodal features efficiently, advancing thorough tissue and patient characterization.
1162. Ficolin-3 Activates Complement and Triggers Necroptosis in Cholangiocarcinoma Cells via the RIPK1/RIPK3/MLKL Signaling Pathway.
作者: Zeyu Zhang.;Maopeng Yin.;Xueyan Geng.;Hongxi Zhao.;Shoucai Zhang.;Yingjie Liu.;Yongyuan Liang.;Jian Ji.;Guixi Zheng.
来源: FASEB J. 2025年39卷10期e70673页
Ficolin 3 (FCN3) is a pattern recognition molecule that activates the complement system via the lectin pathway. While its immunological roles are known, the specific mechanisms by which FCN3 affects cholangiocarcinoma (CCA) pathogenesis remain unclear. In this study, we investigated FCN3 expression in CCA and benign cells, as well as tumor versus non-tumor tissues, using RT-qPCR and Western blotting analyses. The effects of FCN3 on CCA cell proliferation, migration, and invasion were analyzed through CCK-8, EdU, transwell, and wound-healing assays, with in vivo studies supporting these findings. The complement-mediated cytotoxicity of CCA cells was assessed using human serum with or without heat inactivation and an anti-C6 blocking antibody. Immunocytochemical staining was used to examine membrane attack complex (MAC) deposition, and an immunoprecipitation assay was adopted to evaluate the interaction between FCN3 and MASP family members. The role of FCN3 in inducing necroptosis was explored through transmission electron microscopy (TEM) and Western blotting analysis, focusing on the RIPK1/RIPK3/MLKL pathway. The results of the study demonstrate that FCN3 expression was significantly lower in CCA cells and tissues. Overexpressing FCN3 suppressed cell proliferation and migration, enhanced complement-mediated cytotoxicity via MASP2 binding, and increased MAC deposition. FCN3 also induced necroptosis through activating the RIPK1/RIPK3/MLKL pathway. These results highlight FCN3 as a tumor suppressor in CCA and suggest its potential as a therapeutic target for this malignancy.
1163. Suppression of pseudogene MT2P1 transcription induced by E2F7 inhibits hepatocellular carcinoma cell proliferation and facilitates apoptosis via preserving its parental gene.
作者: Yiquan Lu.;Yifan Zhang.;Fengjie Hao.;Nan Wang.;Yongjun Chen.;Junqing Wang.
来源: Cancer Biol Ther. 2025年26卷1期2510035页
The majority of the pseudogenes are inert in normal transcription. Their transcripts are mostly attributed to non-coding RNAs that play various functions in human tumorigenicity and progression. Distinctively, pseudogene MT2P1 is universally transcribed in hepatocytes and presents a significant decrease in hepatocellular carcinoma (HCC). The effect of MT2P1-RNA on HCC cell proliferation and apoptosis needs investigation. MT2P1-RNA was detected by RT-qPCR assay in HCC tissues and cell lines, combined with the exploration of the public databases. The immunohistochemistry assay was used for testing the expression profile of E2F7 and the parental gene MT2A. The clinicopathological features of the patients were collected and analyzed. Ectopic expression of MT2P1-RNA in HCC cell lines was conducted, and the CCK8 assay and flow cytometry assay were carried out. Chromatin immunoprecipitation assay and Dual-luciferase reporter assay were, respectively, applied to validate the interaction between MT2P1, E2F7, and microRNA-15b-5p. The downregulation of MT2P1-RNA in HCC is negatively correlated with dismal clinicopathological features. MT2P1-RNA significantly suppressed HCC cell proliferation and induced apoptosis. E2F7 depletion sequentially elevated the level of MT2P1-RNA and MT2A, and E2F7 was validated as a suppressive transcription factor of the MT2P1 gene. The direct interactions of either MT2P1/miR-15b-5p or miR-15b-5p/MT2A were, respectively, ascertained, enlightening the ceRNA effect of them. The pseudogene-derived MT2P1-RNA is a suppressor of HCC by exerting the ceRNA effect on preserving MT2A, and its transcription is regulated by the suppressive transcription factor E2F7.
1164. Single-Cell RNA-Seq Recognized Key Genes for Metastasis and Macrophage Infiltration in Colorectal Cancer.
Colorectal cancer (CRC) is one of the most common malignancies in the world. However, the main causes of metastasis and immune cell infiltration in CRC are still unclear. This experiment was conducted to identify the key genes of metastasis and macrophage infiltration in CRC according to single-cell sequencing (scRNA-seq) data. By analyzing the data of GSE261012 and GSE234804 in the Gene Expression Omnibus (GEO) database, the key node genes for the stages of tumorigenesis, epithelial-mesenchymal transition, and metastasis of CRC were found. These genes were modeled by lasso regression by The Cancer Genome Atlas (TCGA) database, and ZFAND2A was identified as a key gene for metastasis and macrophage infiltration in CRC. Finally, the specific function of ZFAND2A in cancer cell activity was explored in vitro by qRT-PCR, WB analysis, CCK-8, and transwell assay. The specific function of ZFAND2A in macrophage polarization was explored in vitro by qRT-PCR, ELISA, and flow cytometry. We identified crucial gene expression in the entire process of CRC tumor progression, including tumorigenesis, epithelial-mesenchymal transition, and metastasis. Ten thousand six hundred and thirty-seven genes were determined as genes associated with tumor progression and metastasis. Among them, six genes were identified to be related to CRC prognosis. The results of TCGA data indicated that ZFAND2A showed lower expression in tumors and was related to a good prognosis of CRC. Overexpression of ZFAND2A inhibits the proliferation and migration of CRC cells. Additionally, there was a correlation between ZFAND2A expression and macrophage infiltration. Increasing ZFAND2A promotes M1 polarization in macrophages. Our findings provide new potential biomarkers for the metastatic mechanisms and prognosis of CRC. In addition, ZFAND2A is expected to become a potential therapeutic target for CRC.
1165. Helicobacter pylori induced miR-362-5p upregulation drives gastric cancer progression and links hepatocellular carcinoma through an exosome-dependent pathway.
作者: Jianhui Zhang.;Shuzhen Liu.;Juan Zhang.;Mingzhu Feng.;Shu Chen.;Yinuo Zhang.;Zekun Sun.;Xinying Cao.;Chao Gao.;Xiaofei Ji.;Huilin Zhao.
来源: Front Cell Infect Microbiol. 2025年15卷1582131页
Helicobacter pylori (H. pylori) infection induced miRNA dysregulation plays an important role in gastric cancer (GC) and exosomes mediate the spread of pathogenic effects.
1166. Integrated analysis of microbiome and metabolome reveals insights into cervical neoplasia aggravation in a Chinese cohort.
作者: Qingzhi Zhai.;Luyang Zhao.;Mingyang Wang.;Li Li.;Li-An Li.;Mingxia Ye.;Mingxia Li.;Chengfeng Xu.;Yuanguang Meng.
来源: Front Cell Infect Microbiol. 2025年15卷1556153页
Cervical carcinoma (CC) remains one of the significant cancers threatening women's health globally. Increasing evidence suggests that alterations in the microbiota are closely associated with cancer development. However, the understanding of reliable biomarkers and underlying mechanisms during the aggravation of cervical neoplasia such as cervical intraepithelial neoplasia (CIN) and CC is still relatively limited.
1167. Evaluation of pathological complete response rates in breast cancer patients undergoing neoadjuvant therapy.
作者: Gabriella Ferezini Oliveira de Sá.;Pedro Vilar de Oliveira Villarim.;Pedro Hortêncio Saboia da Escossia Melo.;Ayane Cristine Alves Sarmento.;Ana Katherine Gonçalves.;Kleyton Santos de Medeiros.;Cristina Rocha de Medeiros Miranda.
来源: Rev Bras Ginecol Obstet. 2025年47卷
This study aims to assess the rate of pathological complete response (pCR) in breast cancer patients undergoing neoadjuvant therapy and to explore its correlation with clinical, molecular, and prognostic factors.
1168. Decoding multiple myeloma: single-cell insights into tumor heterogeneity, immune dynamics, and disease progression.
作者: Zhenzhen Zhao.;Zhijie Zhao.;Zhiheng Lin.;Lu Fan.;Zhikai Xiahou.;Yujiang Dong.;Weiying Bao.
来源: Front Immunol. 2025年16卷1584350页
Multiple myeloma (MM) is a biologically heterogeneous malignancy of clonal plasma cells, often progressing from MGUS or smoldering MM. It causes anemia, bone lesions, and immune dysfunction due to abnormal plasma cell expansion in the bone marrow. Neuroinflammatory and neurotrophic factors may influence MM progression by affecting immune cells and the bone marrow niche. Growing evidence points to a role for neuroimmune regulation in tumor immunity. Despite therapeutic progress, disease heterogeneity and resistance highlight the need for new strategies targeting the tumor microenvironment and neuroimmune axis.
1169. A conceptual exploration on the synergistic anti-tumor effects of high-order combination of OHSV2-DSTEFAP5/CD3, CAR-T cells, and immunotoxins in hepatocellular carcinoma.
作者: Shuang Dong.;Xin Chen.;Xiaoyu Li.;Yang Wang.;Qing Huang.;Yuanxiang Li.;Jing Jin.;Xianmin Zhu.;Yi Zhong.;Qian Cai.;Chang Xue.;Fang Guo.;Le Huang.;Mingqian Feng.;Binlei Liu.;Sheng Hu.
来源: Front Immunol. 2025年16卷1509087页
Although the treatment landscape for advanced hepatocellular carcinoma (HCC) has seen significant advancements in the past decade with the introduction of immune checkpoint inhibitors and antiangiogenic drugs, progress has fallen short of expectations. Recently, a novel engineered oncolytic virus (OHSV2) that secretes dual-specific T-cell engagers (DSTEs) targeting the fibroblast activation protein (FAP) was developed and combined with GPC3-targeting CAR-T cells and immunotoxins to exert a synergistic antitumor effect.
1170. High expression of CXCL13 predicts a favorable response to immunotherapy by upregulating CXCR5+CD8+ T-cell infiltration in gastric cancer.
作者: Shuning Xu.;Danyang Li.;Tao Ning.;Yao Lu.;Yansha Sun.;Hua Bai.;Lei Qiao.;Ting Deng.;Ying Liu.
来源: Front Immunol. 2025年16卷1551259页
Identifying predictive biomarkers for immune checkpoint inhibitor (ICI) treatment is critical for gastric cancer (GC) prognosis. C-X-C motif chemokine ligand 13(CXCL13) plays an important role in immune regulation by binding exclusively to its receptor CXCR5. However, its role, underlying mechanisms, and prognostic significance in ICI-treated GC patients remain controversial.
1171. Translating genetics into tissue: inflammatory cytokine-producing TAMs and PD-L1 tumor expression as poor prognosis factors in cutaneous melanoma.
作者: Celia Barrio-Alonso.;Alicia Nieto-Valle.;Lucía Barandalla-Revilla.;José Antonio Avilés-Izquierdo.;Verónica Parra-Blanco.;Paloma Sánchez-Mateos.;Rafael Samaniego.
来源: Front Immunol. 2025年16卷1587545页
Myeloid cells within tumor microenvironments exhibit significant heterogeneity and play a critical role in influencing clinical outcomes. In this study, we investigated the infiltration of various myeloid cell subtypes in a cohort of cutaneous melanomas, revealing no significant correlation between myeloid cell densities and the occurrence of distant metastasis. We further examined the phenotypic characteristics of primary melanoma tumor-associated macrophages (TAMs) utilizing the seven-phenotype classification recently proposed by Ma et al., derived from extensive pan-cancer single-cell RNA-sequencing studies. First, we analyzed the transcriptomic profile of TAMs isolated from stage IV metastasizing primary melanomas, alongside melanoma-conditioned monocytes cultured in vitro, both supporting the inflammatory cytokine-producing macrophage phenotype. Next, we employed multicolor fluorescence confocal microscopy, to assess the expression of TAM phenotype markers at the protein level in a cohort of primary melanoma samples. Notably, markers indicative of the inflammatory TAM phenotype, quantified at single-cell level, were significantly enriched in metastasizing tumors, demonstrating an independent correlation with shorter disease-free and overall survival (log-rank test, p< 0.0002). Additionally, our screening of phenotype markers expression revealed that PD-L1 positivity in tumor cells, rather than in TAMs, was associated with poor prognosis, highlighting a novel aspect of the immune landscape in cutaneous melanoma.
1172. Toll-like receptor 3 activation enhances antitumor immune response in lung adenocarcinoma through NF-κB signaling pathway.
作者: Ang Li.;Man Luo.;Xiyao Liu.;Hongjiao Wu.;Xiaoguang Liu.;Zhi Zhang.;Xuemei Zhang.
来源: Front Immunol. 2025年16卷1585747页
Toll-like receptor 3 (TLR3) is a pattern recognition receptor known to play a crucial role in the immune response to cancer. However, its effect on the efficacy of immunotherapy in lung adenocarcinoma (LUAD) remains unclear. This study aims to investigate the role of TLR3 in LUAD by examining its expression levels, prognostic significance, and impact on immune signaling pathways.
1173. Multi-omics analysis and experiments uncover the link between cancer intrinsic drivers, stemness, and immunotherapy in ovarian cancer with validation in a pan-cancer census.
作者: Yilin Li.;Cen Chen.;Xiaoyu Ji.;Ningxiao Jiang.;Fei Wang.;Xiangqian Gao.;Weiwei Chen.;Qiang Tang.;Yan Li.;Shinan Zhang.;Gaofeng Qin.;Yingjiang Xu.;Yanlin Wang.;Lingwen Kong.;Lei Han.;Jie Mei.
来源: Front Immunol. 2025年16卷1549656页
Although immune checkpoint inhibitors (ICIs) represent a substantial breakthrough in cancer treatment, it is crucial to acknowledge that their efficacy is limited to a subset of patients. The heterogeneity and stemness of cancer render its response to immunotherapy variable, warranting the identification of robust biomarkers for evaluation.
1174. Identification of SCAMP2 as a regulator of NOTCH signaling in cisplatin resistance through a novel prognostic model for bladder cancer.
作者: Longjun Cai.;Shaoqi Zhang.;Fangfang Zheng.;Furong Ji.;Jin Wang.;Long Shi.;Liu Chao.;Xiangyu Wang.;Jianjun Zhang.;Zhiyong Chen.
来源: Front Immunol. 2025年16卷1573412页
Bladder cancer remains a major challenge in clinical oncology, particularly due to the development of platinum resistance, which severely impacts patient prognosis. Despite numerous attempts to create effective prognostic models, their clinical applicability has often been limited.
1175. Oncologic outcomes following neoadjuvant immunochemotherapy in locally advanced oral squamous cell carcinoma.
To assess the oncologic outcomes in patients with oral squamous cell carcinoma (SCC) who underwent treatment with radiotherapy (RT) or chemoradiation therapy (CRT) following neoadjuvant immunochemotherapy and surgery.
1176. Neoadjuvant immunochemotherapy versus neoadjuvant immunoradiotherapy in locally advanced oral squamous cell carcinoma.
To juxtapose the efficacy and safety profiles of neoadjuvant immunochemotherapy (NAIC) and neoadjuvant immunoradiotherapy (NAIR) in the management of locally advanced oral squamous cell carcinoma (SCC).
1177. Case Report: A case of occult insulinoma localized by [18F] FB (ePEG12)12-exendin-4 positron emission tomography with negative findings of selective arterial calcium stimulation test.
作者: Kentaro Sakaki.;Takaaki Murakami.;Hiroyuki Fujimoto.;Yoichi Shimizu.;Kanae Kawai Miyake.;Daisuke Otani.;Shinya Otsuki.;Hironori Shimizu.;Kazuyuki Nagai.;Takumi Nomura.;Daisuke Yabe.;Yuji Nakamoto.;Nobuya Inagaki.
来源: Front Endocrinol (Lausanne). 2025年16卷1556813页
Insulinomas, the most common functional pancreatic neuroendocrine tumors, cause hypoglycemia due to excessive insulin production, leading to severe clinical symptoms like coma or death. Resection surgery is the major curative treatment, but preoperative localization is challenging due to their small size. Traditional imaging methods like computed tomography (CT) and magnetic resonance imaging (MRI) often fail to detect tumors, while more invasive procedures like endoscopic ultrasound tissue acquisition (EUS-TA) and the selective arterial calcium stimulation test (SACST), though informative, depend heavily on operator skill and may not always provide conclusive results. There is an urgent need for non-invasive, sensitive localization methods for insulinomas. Glucagon-like peptide 1 receptor (GLP-1R) targeted PET imaging has emerged as a promising tool. We present a clinical case where [18F] FB (ePEG12)12-exendin-4 positron emission tomography/CT (18F-exendin-4 PET/CT) successfully detected insulinoma, unachievable by conventional imaging, underscoring its potential in guiding minimally invasive surgery.
1178. Repeat robotic nephron-sparing surgery for metachronous multifocal tumors in a solitary kidney: a case report.
作者: Stelian Ianiotescu.;Constantin Gingu.;Irina Balescu.;Nicolae Bacalbasa.;Ioanel Sinescu.
来源: J Med Life. 2025年18卷4期393-396页
We report the case of a 58-year-old male with metachronous renal tumors and a solitary kidney who had previously undergone an open right radical nephrectomy with extended lymphadenectomy for an invasive renal cell carcinoma (RCC) (pT3a N0M0) in November 2013. In May 2022, during routine surveillance, a left lower pole lesion measuring 2.5 × 2 × 1.6 cm was detected, and the patient was submitted to robot-assisted partial nephrectomy (RAPN). The histopathological study confirmed the presence of a pT1a Fuhrman grade 3 clear cell renal carcinoma. In October 2024, follow-up imaging revealed a new upper pole lesion measuring 4 × 3 × 2.3 cm in the left kidney. The patient was submitted to a novel robot-assisted partial nephrectomy, which was successfully completed using selective clamping of the renal artery. The clamping time was 28 minutes (versus 17 minutes during the initial procedure), and the estimated blood loss increased to approximately 300 mL compared to about 100 mL previously, with a console time of 98 minutes. The patient was discharged after the second surgery in good functional status. The final pathology revealed clear cell RCC, Fuhrman grade 2/nucleolar grade 2 (WHO/ISUP 2016), and pT1a, with negative margins. Despite increased technical challenges during reoperation, postoperative renal function remained stable, underscoring the feasibility of repeat RAPN in a solitary kidney.
1179. Prognostic factors and relapse in nodal vs. extranodal non-Hodgkin lymphoma of the ENT region: a prospective cohort study.
作者: Raluca Morar.;Norberth-Istvan Varga.;Claudia Raluca Balasa Virzob.;Nicolae Constantin Balica.;Ioana Delia Horhat.;Alexandru Chioreanu.;Oana Silvana Sarau.;Sonia Tanasescu.;Razvan Susan.;Ion Cristian Mot.
来源: J Med Life. 2025年18卷4期344-350页
Non-Hodgkin Lymphoma (NHL) arising from the ear, nose, and throat (ENT) region presents unique challenges with regard to diagnosis and treatment. This study investigated the clinical characteristics, prognostic factors, and relapse patterns in patients with NHL originating from lymph nodes (nodal NHL) or other extranodal structures, aiming to identify factors associated with relapse between these two groups. This prospective cohort study included 50 patients diagnosed with NHL in the ENT region at a tertiary hospital in South-Western Romania between 2019 and 2021. Patients were categorized as having nodal or extranodal disease based on histopathological examination and were followed for three years to assess disease evolution, including relapse. Cox proportional hazards regression analysis was employed to identify factors associated with relapse-free survival. Extranodal NHL was associated with a significantly higher prevalence of multiple-site involvement compared to nodal NHL (53.3% vs. 30%, P = 0.021). While a trend towards increased relapse was observed in extranodal NHL, this was not statistically significant (P = 0.125). The presence of disseminated disease (HR = 27.295; P < 0.001) and undergoing only a biopsy (compared to total excision, HR = 4.301; P = 0.027) were identified as independent predictors of relapse. Kaplan-Meier analysis demonstrated significantly different relapse-free survival patterns among groups stratified by NHL localization and dissemination status (P < 0.001). The extent of surgical intervention is a crucial factor influencing relapse risk in ENT NHL, with total excision associated with a lower hazard of relapse. At the same time, extranodal involvement may indicate a more aggressive disease course, particularly when combined with dissemination. However, larger studies with longer follow-ups are needed to validate these findings and refine treatment strategies, especially in regions with limited access to healthcare and screening programs.
1180. Optimizing outcomes of partial nephrectomy in patients with tumors in solitary kidneys: a non-systematic review.
作者: Stelian Ianiotescu.;Constantin Gingu.;Alexandru Iordache.;Adrian Preda.;Osama Salloum.;Irina Balescu.;Nicolae Bacalbasa.;Ioanel Sinescu.
来源: J Med Life. 2025年18卷4期270-276页
This review consolidates recent evidence on managing renal cell carcinoma (RCC) in patients with solitary kidneys. It provides a comprehensive discussion of evolving strategies in partial nephrectomy-including open, laparoscopic, and particularly robot-assisted partial nephrectomy (RAPN)-along with thermal and advanced ablative therapies, non-surgical options (such as stereotactic ablative body radiotherapy [SABR] and active surveillance [AS]), and emerging neoadjuvant systemic treatments with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). In addition, the integration of artificial intelligence (AI) for preoperative planning, intraoperative guidance, and postoperative outcome prediction is discussed. Given the limited renal reserve in these patients, preserving functional renal parenchyma is paramount. This multidisciplinary review synthesizes evidence from 2018 to the present and is supported by 70 contemporary references.
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