Cancer Innovation最新文献

{"title":"T-Cadherin in Biliary Tract Cancer Stroma, a Potent Pharmacological Target for Biliary Tract Carcinogenesis","authors":"Yuki Hanamatsu, Chiemi Saigo, Tamotsu Takeuchi","doi":"10.1002/cai2.70001","DOIUrl":"https://doi.org/10.1002/cai2.70001","url":null,"abstract":"<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","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}

{"title":"MOGAN for LUAD Subtype Classification by Integrating Three Omics Data Types","authors":"Haibin He,&nbsp;Longxing Wang,&nbsp;Mingyue Ma","doi":"10.1002/cai2.160","DOIUrl":"https://doi.org/10.1002/cai2.160","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","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/cai2.160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513534","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}

{"title":"The Efficacy and Safety of Pegylated Liposomal Doxorubicin-Based Neoadjuvant Chemotherapy in Children With Osteosarcoma: A Retrospective Real-World Study","authors":"Guoqi Wang,&nbsp;Suoqin Tang,&nbsp;Lina Chai,&nbsp;Yan Liang,&nbsp;Tongtong Li,&nbsp;Wenzhi Bi,&nbsp;Chen Feng","doi":"10.1002/cai2.162","DOIUrl":"https://doi.org/10.1002/cai2.162","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MRI showed that preoperative chemotherapy significantly decreased the coronal tumor width, sagittal anteroposterior diameter, and tumor volume (all <i>p</i> &lt; 0.05), while no significant change was found in tumor length (<i>p</i> &gt; 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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","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/cai2.162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513532","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}

{"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}

{"title":"Artificial Intelligence and Breast Cancer Management: From Data to the Clinic","authors":"Kaixiang Feng,&nbsp;Zongbi Yi,&nbsp;Binghe Xu","doi":"10.1002/cai2.159","DOIUrl":"https://doi.org/10.1002/cai2.159","url":null,"abstract":"<p>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.</p>","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/cai2.159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447118","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}

{"title":"Biological function and mechanism of NAT10 in cancer","authors":"Yufeng Han,&nbsp;Xinxin Zhang,&nbsp;Lei Miao,&nbsp;Huiran Lin,&nbsp;Zhenjian Zhuo,&nbsp;Jing He,&nbsp;Wen Fu","doi":"10.1002/cai2.154","DOIUrl":"10.1002/cai2.154","url":null,"abstract":"<p><i>N</i>-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.</p>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019571","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}

{"title":"Identification of significant single-nucleotide polymorphisms associated with breast cancer recurrence and metastasis using GWAS","authors":"Shujuan Sun,&nbsp;Sha Yin,&nbsp;Jie Huang,&nbsp;Dongdong Zhou,&nbsp;Qiaorui Tan,&nbsp;Xiaochu Man,&nbsp;Wen Wang,&nbsp;Jiale Zhang,&nbsp;Huihui Li","doi":"10.1002/cai2.142","DOIUrl":"10.1002/cai2.142","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Based on the GWAS results, 191 SNP-related genes significantly associated with BC recurrence and metastasis were identified as expression quantitivative trait loci (<i>p</i> &lt; 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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961077","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}

{"title":"lncRNA TCONS_00251376 promotes the proliferation and migration of gastric cancer cell through upregulating ETV1","authors":"Dengfeng Ren,&nbsp;Fuxing Zhao,&nbsp;Jinming Li,&nbsp;Xinjian Guo,&nbsp;Xinfu Ma,&nbsp;Yonghui Zheng,&nbsp;Guoshuang Shen,&nbsp;Jiuda Zhao","doi":"10.1002/cai2.156","DOIUrl":"10.1002/cai2.156","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although there have been significant advancements in the treatment modalities for gastric cancer (GC) in recent years, the overall prognosis remains poor, particularly for individuals in advanced stages. The absence of a sensitive tumor marker in GC is a crucial factor contributing to this challenge.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Our study focused on investigating a newly discovered long noncoding RNA (lncRNA) known as TCONS_00251376, which has been confirmed to exhibit differential expression in GC compared to adjacent tissues. To further validate these expression differences, we collected 22 pairs of GC and adjacent noncancerous tissues. Subsequent cell function experiments and animal studies were conducted to elucidate the role and underlying mechanisms of lncRNA TCONS_00251376 in the development of GC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study revealed a significant upregulation of lncRNA TCONS_00251376 in cancer tissues (<i>p </i>&lt; 0.01) and a consistent upregulation in GC cell lines (AGS, MKN45, BGC-823, and MGC-803). Furthermore, it was observed that lncRNA TCONS_00251376 played a promotive role in the proliferation, migration, and invasion of GC cells. Subsequent analysis indicated that lncRNA TCONS_00251376 could upregulate the expression of ETV1, a factor associated with the prognosis of GC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Therefore, our findings suggest that lncRNA TCONS_00251376 functions as an oncogenic lncRNA, promoting tumorigenesis and progression by regulating the expression of ETV1 gene. This highlights its potential as an effective target for treating GC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11636580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820501","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}

{"title":"Expression pattern and prognostic significance of aldehyde dehydrogenase 2 in lung adenocarcinoma as a potential predictor of immunotherapy efficacy","authors":"Silvia Baldari,&nbsp;Annalisa Antonini,&nbsp;Giuliana Di Rocco,&nbsp;Gabriele Toietta","doi":"10.1002/cai2.149","DOIUrl":"10.1002/cai2.149","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The incidence of alcohol-associated cancers is higher within Asian populations having an increased prevalence of an inactivating mutation in aldehyde dehydrogenase 2 (<i>ALDH2</i>), a mitochondrial enzyme required for the clearance of acetaldehyde, a cytotoxic metabolite of ethanol. The role of alcohol consumption in promoting lung cancer is controversial, and little attention has been paid to the association between alcohol drinking and pulmonary ALDH2 expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a comprehensive bioinformatic analysis of multi-omics data available in public databases to elucidate the role of ALDH2 in lung adenocarcinoma (LUAD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Transcriptional and proteomic data indicate a substantial pulmonary expression of ALDH2, which is functional for the metabolism of alcohol diffused from the bronchial circulation. ALDH2 expression is higher in healthy lung tissue than in LUAD and inhibits cell cycle, apoptosis, and epithelial–mesenchymal transition pathways. Moreover, low <i>ALDH2</i> mRNA levels predict poor prognosis and low overall survival in LUAD patients. Interestingly, ALDH2 expression correlates with immune infiltration in LUAD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A better understanding of the role of ALDH2 in lung tumor progression and immune infiltration might support its potential use as a prognostic marker and therapeutic target for improving immunotherapeutic response.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11620833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788362","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}

{"title":"Subtype-specific transcription factors affect polyamine metabolism and the tumor microenvironment in breast cancer","authors":"Qi Song,&nbsp;Yixuan Wang,&nbsp;Sen Liu","doi":"10.1002/cai2.138","DOIUrl":"https://doi.org/10.1002/cai2.138","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Polyamines play important roles in cell growth and proliferation. Polyamine metabolism genes are dysregulated in various tumors. Some polyamine metabolism genes are regulated by transcription factors. However, the transcription factors that regulate polyamine metabolism genes have not been completely identified. Additionally, whether any of the transcriptional regulations depend on tumor heterogeneity and the tumor microenvironment has not been investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used bulk RNA-seq data to identify dysregulated polyamine metabolism genes and their transcription factors across breast cancer subtypes. Genes highly correlated with polyamine changes were obtained, and their subtype-specific expressions were checked in tumor microenvironment cells using single-cell RNA (scRNA)-seq data. Gene Ontology enrichment analysis was used to explore their molecular functions and biological processes, and survival analysis was used to examine the impact of these genes on therapeutic outcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We first analyzed the dysregulation of polyamine synthesis, catabolism, and transport in four breast cancer subtypes. Genes such as <i>AGMAT</i> and <i>CAV1</i> were dysregulated across all subtypes, while <i>APRT</i>, <i>SAT1</i>, and other genes were dysregulated in the more lethal subtypes. Among the dysregulated genes of polyamine metabolism, we focused on three genes (<i>SRM</i>, <i>APRT</i>, and <i>SAT1</i>) and identified their transcription factors (SPI1 and IRF1 correspond to <i>SAT1</i>, and IRF3 corresponds to <i>SRM</i> and <i>APRT</i>). With scRNA-seq data, we verified that these three transcription factors also regulated these three polyamine metabolism genes in the tumor microenvironment. Both bulk RNA-seq and scRNA-seq data indicated that these genes were specifically upregulated in high-risk breast cancer subtypes, such as the basal-like type. High expression of these genes corresponded to worse outcomes in the basal-like subtype under chemotherapy and radiation treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our work identified three subtype-specific transcription factors that regulate three polyamine metabolism genes in high-risk breast cancer subtypes and the tumor microenvironment. Our results deepen the understanding of the role of polyamine metabolism in breast cancer and may help the clinical therapy of advanced breast cancer subtypes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.138","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762076","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}