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Inhibition of Putative Ibrutinib Targets Promotes Atrial Fibrillation, Conduction Blocks, and Proarrhythmic Electrocardiogram Indices: A Mendelian Randomization Analysis
Pub Date : 2025-03-12 DOI: 10.1002/cai2.70004
Hongxuan Xu, Bingxun Li, Pinchao Lv, Ying Chen, Yanyun Lin, An Zhang, Jing Zhao, Guoxiong Zhou, Lin Wu

Background

The mechanism by which ibrutinib, a Bruton's tyrosine kinase inhibitor, can elevate the risk of arrhythmias is not fully elucidated. In this study, we explored how inhibition of off-target kinases can contribute to this phenomenon.

Methods

We performed a Mendelian randomization analysis to examine the causal associations between genetically proxied inhibition of six putative ibrutinib drug targets (ErbB2/HER2, CSK, JAK3, TEC, BLK, and PLCG2) and the atrial fibrillation (AF) risk, proarrhythmic ECG indices, and cardiometabolic traits and diseases. Inverse-variance weighted random-effects models and Wald ratio were used to examine the associations between genetically proxied inhibition of these drug targets and the risk of outcomes. Colocalization analyses were employed to examine the robustness of the causally significant findings. ELISAs were used to measure ErbB2 levels in intracardiac plasma samples.

Results

Genetically proxied ErbB2 inhibition was associated with an increased AF risk, higher P wave terminal force, and prolonged QTc interval. Patients with AF had significantly higher intracardiac ErbB2 levels compared with patients with paroxysmal supraventricular tachycardia. CSK inhibition prolonged the QRS duration, decreased the QTc interval, and was potentially linked to conduction blocks. PLCG2 inhibition led to decreased P wave terminal force, shorter QTc interval, and increased risk of left bundle branch block. BLK inhibition shortened the QTc interval and was also associated with atrioventricular block.

Conclusion

The off-target effects and downstream targets of ibrutinib, including CSK, PLCG2, ERBB2, TEC, and BLK, may lead to cardiac electrical homeostasis imbalances and lethal cardiovascular diseases. Using drugs that inhibit these targets should be given extra caution.

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引用次数: 0
Computed Tomography-Based Habitat Analysis for Prognostic Stratification in Colorectal Liver Metastases
Pub Date : 2025-03-12 DOI: 10.1002/cai2.70000
Chaoqun Zhou, Hao Xin, Lihua Qian, Yong Zhang, Jing Wang, Junpeng Luo

Background

Colorectal liver metastasis (CRLM) has a poor prognosis, and traditional prognostic models have certain limitations in clinical application. This study aims to evaluate the prognostic value of CT-based habitat analysis in CRLM patients and compare it with existing traditional prognostic models to provide more evidence for individualized treatment of CRLM patients.

Methods

This retrospective study included 197 patients with CRLM whose preoperative contrast-enhanced CT images and corresponding DICOM Segmentation Objects (DSOs) were obtained from The Cancer Imaging Archive (TCIA). Tumor regions were segmented, and habitat features representing distinct subregions were extracted. An unsupervised K-means clustering algorithm classified the tumors into two clusters based on their habitat characteristics. Kaplan–Meier analysis was used to evaluate overall survival (OS), disease-free survival (DFS), and liver-specific DFS. The habitat model's predictive performance was compared with the Clinical Risk Score (CRS) and Tumor Burden Score (TBS) using the concordance index (C-index), Integrated Brier Score (IBS), and time-dependent area under the curve (AUC).

Results

The habitat model identified two distinct patient clusters with significant differences in OS, DFS, and liver-specific DFS (p < 0.01). Compared with CRS and TBS, the habitat model demonstrated superior predictive accuracy, particularly for DFS and liver-specific DFS, with higher time-dependent AUC values and improved model calibration (lower IBS).

Conclusions

CT-based habitat analysis captures spatial tumor heterogeneity and provides enhanced prognostic stratification in CRLM. The method outperforms conventional models and offers potential for more personalized treatment planning.

{"title":"Computed Tomography-Based Habitat Analysis for Prognostic Stratification in Colorectal Liver Metastases","authors":"Chaoqun Zhou,&nbsp;Hao Xin,&nbsp;Lihua Qian,&nbsp;Yong Zhang,&nbsp;Jing Wang,&nbsp;Junpeng Luo","doi":"10.1002/cai2.70000","DOIUrl":"https://doi.org/10.1002/cai2.70000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Colorectal liver metastasis (CRLM) has a poor prognosis, and traditional prognostic models have certain limitations in clinical application. This study aims to evaluate the prognostic value of CT-based habitat analysis in CRLM patients and compare it with existing traditional prognostic models to provide more evidence for individualized treatment of CRLM patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study included 197 patients with CRLM whose preoperative contrast-enhanced CT images and corresponding DICOM Segmentation Objects (DSOs) were obtained from The Cancer Imaging Archive (TCIA). Tumor regions were segmented, and habitat features representing distinct subregions were extracted. An unsupervised K-means clustering algorithm classified the tumors into two clusters based on their habitat characteristics. Kaplan–Meier analysis was used to evaluate overall survival (OS), disease-free survival (DFS), and liver-specific DFS. The habitat model's predictive performance was compared with the Clinical Risk Score (CRS) and Tumor Burden Score (TBS) using the concordance index (C-index), Integrated Brier Score (IBS), and time-dependent area under the curve (AUC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The habitat model identified two distinct patient clusters with significant differences in OS, DFS, and liver-specific DFS (<i>p</i> &lt; 0.01). Compared with CRS and TBS, the habitat model demonstrated superior predictive accuracy, particularly for DFS and liver-specific DFS, with higher time-dependent AUC values and improved model calibration (lower IBS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CT-based habitat analysis captures spatial tumor heterogeneity and provides enhanced prognostic stratification in CRLM. The method outperforms conventional models and offers potential for more personalized treatment planning.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immunological Effects of Proton Radiotherapy: New Opportunities and Challenges in Cancer Therapy
Pub Date : 2025-03-07 DOI: 10.1002/cai2.70003
Anhang Zhang, Liyuan Fan, Qi Liu, Xiaoxin Zuo, Jian Zhu

Radiation therapy can be categorised by particle type into photon, proton and heavy ion therapies. Proton radiotherapy is highlighted due to its unique physical properties, such as the Bragg peak and minimal exit dose, which offer superior dose distribution. This makes proton radiotherapy especially advantageous for treating tumours near vital organs with complex structures, such as gliomas near the brain, nasopharyngeal carcinoma near the brainstem and mediastinal tumours near the heart. Proton irradiation can induce distant effects through immunogenicity within the target area. The reduced low-dose zone outside the target provides better lymphatic system protection and immune benefits. Additionally, combining proton radiotherapy with immunotherapy may offer further biological advantages. These features make proton radiotherapy a promising option in cancer treatment. This article may aid in the understanding of proton radiotherapy and its immune effects and lead to new effective options for tumour treatment.

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引用次数: 0
T-Cadherin in Biliary Tract Cancer Stroma, a Potent Pharmacological Target for Biliary Tract Carcinogenesis
Pub Date : 2025-02-28 DOI: 10.1002/cai2.70001
Yuki Hanamatsu, Chiemi Saigo, Tamotsu Takeuchi
<p>Based on the empirical data, we propose that T-cadherin could be a molecular target for disrupting the stroma of patients with biliary tract cancer (BTC).</p><p>BTC comprises carcinomas originating in the bile ducts, including cholangiocarcinomas (cancers arising in the intrahepatic or extrahepatic bile ducts) and gallbladder carcinomas [<span>1</span>]. BTC often exhibits an aggressive clinicopathological course [<span>1</span>]. Surgical resection remains the most curative treatment option for patients with BTC; however, it may be limited to the early stages of cancer [<span>1</span>]. Owing to their poor sensitivity to chemotherapeutic agents, new therapeutic approaches are required for patients with advanced BTC.</p><p>One of the remarkable pathological features of BTC is the dense fibrous stroma harboring cancer cell nests. It is well established that stromal cells play a crucial role in the tumor microenvironment. Therefore, several targeting therapies are attempted against cancer stroma. For example, lysyl oxidases (LOXs) are a family of five secreted copper-dependent amine oxidases (LOX and LOXL1–4) that promote carcinogenesis by generating cancer stroma. Very recently, Burchard et al. [<span>2</span>] demonstrated that PXS-5505, which is a small molecule inhibitor of all LOX isoforms, improved chemotherapeutic penetration and reduced the inflammatory reaction of intrahepatic cholangiocarcinoma, thereby enhancing antitumor immunity in autochthonous and orthotopic murine models. Unfortunately, efforts to target individual LOX isoforms have failed to achieve clinical impact, likely due to the compensatory action of other LOX family members. Combination therapies targeting multiple stromal components are warranted.</p><p>T-cadherin is an atypical cadherin attached to the plasma membrane by a glycosylphosphatidylinositol anchor without a cytosolic domain [<span>2</span>]. Notably, it is overexpressed in endothelial cells of tumor-penetrating vessels in several malignant tumors [<span>3, 4</span>].</p><p>In this study, we investigated whether T-cadherin was also expressed in the tumor endothelial cells of BTC. Immunohistochemical staining using a tissue microarray, with a core diameter of 1.5 mm, demonstrated T-cadherin immunoreactivity in cancer stromal niches in BTC, especially in the cancer invasion microenvironment with a desmoplastic reaction (Figure 1a–d). Furthermore, T-cadherin expression was detected in the endothelial cells of tumor vessels and stromal mesenchymal cells of all 27 intrahepatic cholangiocarcinomas and 32 of 43 extrahepatic biliary duct adenocarcinomas. Consistent with previous research [<span>3</span>], T-cadherin immunoreactivity was also observed in the endothelial cells of tumor-penetrating vessels in breast and colorectal cancers. However, little T-cadherin immunoreactivity was observed in the stromal mesenchymal cells of these cancers (Figure 1e,f).</p><p>Here, we could not unravel whether stromal T-cadherin ex
{"title":"T-Cadherin in Biliary Tract Cancer Stroma, a Potent Pharmacological Target for Biliary Tract Carcinogenesis","authors":"Yuki Hanamatsu,&nbsp;Chiemi Saigo,&nbsp;Tamotsu Takeuchi","doi":"10.1002/cai2.70001","DOIUrl":"https://doi.org/10.1002/cai2.70001","url":null,"abstract":"&lt;p&gt;Based on the empirical data, we propose that T-cadherin could be a molecular target for disrupting the stroma of patients with biliary tract cancer (BTC).&lt;/p&gt;&lt;p&gt;BTC comprises carcinomas originating in the bile ducts, including cholangiocarcinomas (cancers arising in the intrahepatic or extrahepatic bile ducts) and gallbladder carcinomas [&lt;span&gt;1&lt;/span&gt;]. BTC often exhibits an aggressive clinicopathological course [&lt;span&gt;1&lt;/span&gt;]. Surgical resection remains the most curative treatment option for patients with BTC; however, it may be limited to the early stages of cancer [&lt;span&gt;1&lt;/span&gt;]. Owing to their poor sensitivity to chemotherapeutic agents, new therapeutic approaches are required for patients with advanced BTC.&lt;/p&gt;&lt;p&gt;One of the remarkable pathological features of BTC is the dense fibrous stroma harboring cancer cell nests. It is well established that stromal cells play a crucial role in the tumor microenvironment. Therefore, several targeting therapies are attempted against cancer stroma. For example, lysyl oxidases (LOXs) are a family of five secreted copper-dependent amine oxidases (LOX and LOXL1–4) that promote carcinogenesis by generating cancer stroma. Very recently, Burchard et al. [&lt;span&gt;2&lt;/span&gt;] demonstrated that PXS-5505, which is a small molecule inhibitor of all LOX isoforms, improved chemotherapeutic penetration and reduced the inflammatory reaction of intrahepatic cholangiocarcinoma, thereby enhancing antitumor immunity in autochthonous and orthotopic murine models. Unfortunately, efforts to target individual LOX isoforms have failed to achieve clinical impact, likely due to the compensatory action of other LOX family members. Combination therapies targeting multiple stromal components are warranted.&lt;/p&gt;&lt;p&gt;T-cadherin is an atypical cadherin attached to the plasma membrane by a glycosylphosphatidylinositol anchor without a cytosolic domain [&lt;span&gt;2&lt;/span&gt;]. Notably, it is overexpressed in endothelial cells of tumor-penetrating vessels in several malignant tumors [&lt;span&gt;3, 4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;In this study, we investigated whether T-cadherin was also expressed in the tumor endothelial cells of BTC. Immunohistochemical staining using a tissue microarray, with a core diameter of 1.5 mm, demonstrated T-cadherin immunoreactivity in cancer stromal niches in BTC, especially in the cancer invasion microenvironment with a desmoplastic reaction (Figure 1a–d). Furthermore, T-cadherin expression was detected in the endothelial cells of tumor vessels and stromal mesenchymal cells of all 27 intrahepatic cholangiocarcinomas and 32 of 43 extrahepatic biliary duct adenocarcinomas. Consistent with previous research [&lt;span&gt;3&lt;/span&gt;], T-cadherin immunoreactivity was also observed in the endothelial cells of tumor-penetrating vessels in breast and colorectal cancers. However, little T-cadherin immunoreactivity was observed in the stromal mesenchymal cells of these cancers (Figure 1e,f).&lt;/p&gt;&lt;p&gt;Here, we could not unravel whether stromal T-cadherin ex","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
MOGAN for LUAD Subtype Classification by Integrating Three Omics Data Types
Pub Date : 2025-02-28 DOI: 10.1002/cai2.160
Haibin He, Longxing Wang, Mingyue Ma

Background

Lung adenocarcinoma (LUAD) is a highly heterogeneous cancer type with a poor prognosis. Accurate subtype identification can help guide its treatment. The traditional subtype identification methods using a single-omics approach make it difficult to comprehensively characterize the molecular features of LUAD. Identification of subtypes through multi-omics association strategies can effectively supplement the shortcomings of single-omics information.

Methods

In this study, we used the Generative Adversarial Network (GAN) to mine transcriptomic, proteomic, and epigenomic information and generate an integrated data set. The newly integrated data were then used to identify LUAD immune subtypes. In the improved GAN (MOGAN) method, we not only integrated multiple omics datasets but also included the interactions between proteins and genes and between methylation and genes. Thus, we achieved effective complementarity of multi-omics information.

Results

Two subtypes, MOGANTPM_S1 and MOGANTPM_S2, were identified using immune cell infiltration analysis and the integrated multi-omics data. MOGANTPM_S1 patients displayed higher immune cell infiltration, better prognosis, and sensitivity to immune checkpoint inhibitors (ICIs), while MOGANTPM_S2 had lower immune cell infiltration, poorer prognosis, and were insensitive to ICIs. Therefore, immunotherapy was more suitable for MOGANTPM_S1 patients in clinical practice. In addition, this study developed a LUAD subtype diagnostic model using the transcriptomic and proteomic features of five genes, which can be used to guide clinical subtype diagnosis.

Conclusions

In summary, the MOGAN method was applied to integrate three omics data types and successfully identify two LUAD immune subtypes with significant survival differences. This classification method may be useful for LUAD treatment decisions.

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引用次数: 0
The Efficacy and Safety of Pegylated Liposomal Doxorubicin-Based Neoadjuvant Chemotherapy in Children With Osteosarcoma: A Retrospective Real-World Study
Pub Date : 2025-02-28 DOI: 10.1002/cai2.162
Guoqi Wang, Suoqin Tang, Lina Chai, Yan Liang, Tongtong Li, Wenzhi Bi, Chen Feng

Background

Treatment of osteosarcoma in children remains difficult. The combination of chemotherapy and surgery is the classic treatment for osteosarcoma. With the development of medicine, chemotherapy has also improved greatly. This study aimed to explore the short-term efficacy and safety of neoadjuvant chemotherapy (NAC) with a protocol of pegylated liposomal doxorubicin (PLD), high-dose methotrexate, and ifosfamide (PLDMI) in pediatric patients with osteosarcoma.

Methods

Between May 1, 2018 and May 1, 2021, 25 pediatric patients with osteosarcoma were included in this retrospective, observational study. All patients received PLDMI including PLD, high-dose methotrexate, and ifosfamide, followed by surgery and postoperative chemotherapy. Tumor parameters at the time of preoperative chemotherapy were evaluated by the investigator using MRI, and the response to preoperative chemotherapy was scored according to the Huvos grading system. Short-term survival was analyzed by a Cox proportional hazard model. Safety was assessed as adverse events (AEs) by the Common Terminology Criteria for AEs version 5.0.

Results

MRI showed that preoperative chemotherapy significantly decreased the coronal tumor width, sagittal anteroposterior diameter, and tumor volume (all p < 0.05), while no significant change was found in tumor length (p > 0.05). More than 90% of tumor necrosis was achieved in 13 (61.9%, 13/21) patients. The 2-year overall survival and disease-free survival rates were 92% and 76%, respectively. Cox regression analysis identified pathological type and imaging at the time of completion of treatment as independent prognostic factors for children with osteosarcoma. Grade 3–4 AEs included febrile neutropenia (25/25, 100%), secondary anemia (18/25, 72%), secondary thrombocytopenia (20/25, 80%), and mucositis with local infection (3/25, 12%), which were resolved with symptomatic treatment.

Conclusions

PLDMI was an effective protocol for children with osteosarcoma and could effectively reduce the tumor burden in the primary site and augment surgical treatment, although with a high incidence of AEs.

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引用次数: 0
Predictive Value of Neutrophil-to-Lymphocyte Ratio for Immune Checkpoint Inhibitor-Related Myocarditis Among Patients Treated for Non-Small-Cell Lung Cancer
Pub Date : 2025-02-20 DOI: 10.1002/cai2.163
Jian Xue, Chuanbin Liu, Jun Shao, Li Wang, Yating Han, Jing Wang, Jinda Wang

Background

The predictive value of the neutrophil-to-lymphocyte ratio (NLR) for immune checkpoint inhibitors (ICIs) in various tumors remains uncertain despite its use in forecasting the effectiveness of immunotherapy. The purpose of our research was to determine the prognostic significance of NLR for immune checkpoint inhibitor-related myocarditis in non-small-cell lung cancer (NSCLC) patients.

Methods

We enrolled and monitored patients with NSCLC who received ICI therapy at the Fifth Medical Center of Chinese PLA General Hospital between January 1, 2018, and February 20, 2021. NLR was determined before and soon after each cycle of ICIs. All participants in this study were periodically examined for troponin and brain natriuretic peptide (BNP), and an electrocardiogram (ECG) and echocardiography were done. Cox's proportional hazards regression model and receiver operating characteristic (ROC) were used to assess the predictive value for ICI-related myocarditis.

Results

A total of 146 patients received ICI treatment and completed a follow-up. Of these, 17 patients (11.64%) developed ICI-related myocarditis that met the diagnostic criteria. The initial cycle revealed that the NLR was a reliable predictor of potential myocarditis related to ICIs, with an area under the curve (AUC) of 0.833 and a 95% confidence interval (CI) of 0.721–0.945. Following the initial round of ICI treatment, an NLR elevation (NLR ≥ 3.25) appeared to be the most significant standalone indicator of ICI-related myocarditis (HR: 11.094; 95% CI: 3.186–38.631; p < 0.001).

Conclusions

Our study confirmed that NLR elevation in the early phase after ICI treatment of NSCLC is a reliable predictive factor of ICI-related myocarditis. Regular and frequent cardiac monitoring may help to avoid the occurrence of severe and fatal cases.

{"title":"Predictive Value of Neutrophil-to-Lymphocyte Ratio for Immune Checkpoint Inhibitor-Related Myocarditis Among Patients Treated for Non-Small-Cell Lung Cancer","authors":"Jian Xue,&nbsp;Chuanbin Liu,&nbsp;Jun Shao,&nbsp;Li Wang,&nbsp;Yating Han,&nbsp;Jing Wang,&nbsp;Jinda Wang","doi":"10.1002/cai2.163","DOIUrl":"https://doi.org/10.1002/cai2.163","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The predictive value of the neutrophil-to-lymphocyte ratio (NLR) for immune checkpoint inhibitors (ICIs) in various tumors remains uncertain despite its use in forecasting the effectiveness of immunotherapy. The purpose of our research was to determine the prognostic significance of NLR for immune checkpoint inhibitor-related myocarditis in non-small-cell lung cancer (NSCLC) patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We enrolled and monitored patients with NSCLC who received ICI therapy at the Fifth Medical Center of Chinese PLA General Hospital between January 1, 2018, and February 20, 2021. NLR was determined before and soon after each cycle of ICIs. All participants in this study were periodically examined for troponin and brain natriuretic peptide (BNP), and an electrocardiogram (ECG) and echocardiography were done. Cox's proportional hazards regression model and receiver operating characteristic (ROC) were used to assess the predictive value for ICI-related myocarditis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 146 patients received ICI treatment and completed a follow-up. Of these, 17 patients (11.64%) developed ICI-related myocarditis that met the diagnostic criteria. The initial cycle revealed that the NLR was a reliable predictor of potential myocarditis related to ICIs, with an area under the curve (AUC) of 0.833 and a 95% confidence interval (CI) of 0.721–0.945. Following the initial round of ICI treatment, an NLR elevation (NLR ≥ 3.25) appeared to be the most significant standalone indicator of ICI-related myocarditis (HR: 11.094; 95% CI: 3.186–38.631; <i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study confirmed that NLR elevation in the early phase after ICI treatment of NSCLC is a reliable predictive factor of ICI-related myocarditis. Regular and frequent cardiac monitoring may help to avoid the occurrence of severe and fatal cases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.163","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Artificial Intelligence and Breast Cancer Management: From Data to the Clinic
Pub Date : 2025-02-20 DOI: 10.1002/cai2.159
Kaixiang Feng, Zongbi Yi, Binghe Xu

Breast cancer (BC) remains a significant threat to women's health worldwide. The oncology field had an exponential growth in the abundance of medical images, clinical information, and genomic data. With its continuous advancement and refinement, artificial intelligence (AI) has demonstrated exceptional capabilities in processing intricate multidimensional BC-related data. AI has proven advantageous in various facets of BC management, encompassing efficient screening and diagnosis, precise prognosis assessment, and personalized treatment planning. However, the implementation of AI into precision medicine and clinical practice presents ongoing challenges that necessitate enhanced regulation, transparency, fairness, and integration of multiple clinical pathways. In this review, we provide a comprehensive overview of the current research related to AI in BC, highlighting its extensive applications throughout the whole BC cycle management and its potential for innovative impact. Furthermore, this article emphasizes the significance of constructing patient-oriented AI algorithms. Additionally, we explore the opportunities and potential research directions within this burgeoning field.

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引用次数: 0
Biological function and mechanism of NAT10 in cancer NAT10在肿瘤中的生物学功能及机制。
Pub Date : 2025-01-14 DOI: 10.1002/cai2.154
Yufeng Han, Xinxin Zhang, Lei Miao, Huiran Lin, Zhenjian Zhuo, Jing He, Wen Fu

N-acetyltransferase 10 (NAT10) is a nucleolar acetyltransferase with an acetylation catalytic function and can bind various protein and RNA molecules. As the N4-acetylcytidine (ac4C) “writer” enzyme, NAT10 is reportedly involved in a variety of physiological and pathological activities. Currently, the NAT10-related molecular mechanisms in various cancers are not fully understood. In this review, we first describe the cellular localization of NAT10 and then summarize its numerous biological functions. NAT10 is involved in various biological processes by mediating the acetylation of different proteins and RNAs. These biological functions are also associated with cancer progression and patient prognosis. We also review the mechanisms by which NAT10 plays roles in various cancer types. NAT10 can affect tumor cell proliferation, metastasis, and stress tolerance through its acetyltransferase properties. Further research into NAT10 functions and expression regulation in tumors will help explore its future potential in cancer diagnosis, treatment, and prognosis.

n -乙酰基转移酶10 (NAT10)是一种具有乙酰化催化功能的核仁乙酰基转移酶,可结合多种蛋白质和RNA分子。作为n4 -乙酰胞苷(ac4C)据报道,“writer”酶NAT10参与多种生理和病理活动。目前,nat10在各种癌症中的相关分子机制尚不完全清楚。在这篇综述中,我们首先描述了NAT10的细胞定位,然后总结了其众多的生物学功能。NAT10通过介导不同蛋白质和rna的乙酰化参与多种生物过程。这些生物学功能也与癌症进展和患者预后有关。我们还回顾了NAT10在各种癌症类型中发挥作用的机制。NAT10可以通过其乙酰转移酶特性影响肿瘤细胞的增殖、转移和应激耐受。进一步研究NAT10在肿瘤中的功能和表达调控,将有助于挖掘其在癌症诊断、治疗和预后方面的潜力。
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引用次数: 0
Identification of significant single-nucleotide polymorphisms associated with breast cancer recurrence and metastasis using GWAS 使用GWAS鉴定与乳腺癌复发和转移相关的显著单核苷酸多态性。
Pub Date : 2025-01-07 DOI: 10.1002/cai2.142
Shujuan Sun, Sha Yin, Jie Huang, Dongdong Zhou, Qiaorui Tan, Xiaochu Man, Wen Wang, Jiale Zhang, Huihui Li

Background

Identification of risk genes and loci associated with the recurrence and metastasis of breast cancer (BC) is of utmost importance. Genome-wide association studies (GWASs) represent valuable tools for identifying the disease risk associated with a given single-nucleotide polymorphism (SNP); they offer significant insights into the disease progression mechanism by analyzing SNP information of the entire genome. Though GWAS has already identified several genetic susceptibility SNPs for BC, their significance in the recurrence and metastasis of this cancer remains unclear. Here, we used a GWAS approach to identify SNPs specifically associated with the risk of BC recurrence and metastasis.

Methods

This study adopted a two-stage GWAS approach. In the first stage, 97 pairs of BC patients with or without recurrence and metastasis, treated at the Shandong Cancer Hospital and Institute from November 2013 to April 2014, were identified using propensity score matching. DNA extracted from the patient peripheral blood was then subjected to Illumina ASA chip analysis for genome-wide SNP detection. In the second stage, the findings were verified in a validation set of 854 BC patients recruited at the same hospital from May 2014 to June 2015. SNP genotyping was performed using time-of-flight mass spectrometry. The SNP loci and their corresponding genes and pathways were analyzed using the DAVID (https://david.ncifcrf.gov/) online enrichment analysis tool.

Results

Based on the GWAS results, 191 SNP-related genes significantly associated with BC recurrence and metastasis were identified as expression quantitivative trait loci (p < 0.001). Functional and pathway enrichment analyses subsequently revealed the potential involvement of glutamatergic synaptic transmission, calcium signaling, and insulin secretion pathways in BC recurrence and metastasis. Based on genotype correlation and database expression levels, rs10108514, rs12920540, rs4273077, and rs4730155 were found to be significantly associated with the risk of BC recurrence and metastasis.

Conclusion

Our study suggests that the SNPs rs10108514, rs12920540, rs4273077, and rs4730155 are correlated with the risk of BC recurrence and metastasis, potentially by being implicated in glutamatergic synaptic transmission, calcium signaling, and insulin secretion pathways.

背景:确定与乳腺癌(BC)复发和转移相关的危险基因和基因座是至关重要的。全基因组关联研究(GWASs)是识别与给定单核苷酸多态性(SNP)相关的疾病风险的有价值的工具;它们通过分析整个基因组的SNP信息,为疾病进展机制提供了重要的见解。虽然GWAS已经确定了几个BC的遗传易感性snp,但它们在这种癌症的复发和转移中的意义尚不清楚。在这里,我们使用GWAS方法来鉴定与BC复发和转移风险特异性相关的snp。方法:本研究采用两阶段GWAS方法。第一阶段选取2013年11月至2014年4月在山东省肿瘤医院和肿瘤研究所治疗的97对有或无复发转移的BC患者,采用倾向评分匹配法进行鉴定。从患者外周血中提取DNA,然后进行Illumina ASA芯片分析,进行全基因组SNP检测。在第二阶段,研究结果在2014年5月至2015年6月在同一家医院招募的854名BC患者的验证集中得到验证。使用飞行时间质谱法进行SNP基因分型。使用DAVID (https://david.ncifcrf.gov/)在线富集分析工具分析SNP位点及其对应的基因和通路。结果:基于GWAS结果,191个与BC复发和转移相关的snp相关基因被确定为表达定量性状位点(p)。结论:我们的研究提示snp rs10108514、rs12920540、rs4273077和rs4730155与BC复发和转移风险相关,可能与谷氨酸能突触传递、钙信号传导和胰岛素分泌途径有关。
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引用次数: 0
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Cancer Innovation
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