Boyue Han, Xiangchen Han, Hong Luo, Javaria Nasir, Chao Chen, Zhiming Shao, Hong Ling, Xin Hu
{"title":"Multiomics and single-cell sequencings reveal the specific biological characteristics of low Ki-67 triple-negative breast cancer","authors":"Boyue Han, Xiangchen Han, Hong Luo, Javaria Nasir, Chao Chen, Zhiming Shao, Hong Ling, Xin Hu","doi":"10.1002/cai2.146","DOIUrl":"https://doi.org/10.1002/cai2.146","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Triple-negative breast cancer (TNBC) displays high heterogeneity. The majority of TNBC cases are characterized by high Ki-67 expression. TNBC with low Ki-67 expression accounts for only a small fraction of cases and has been relatively less studied.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study analyzed a large single-center multiomics TNBC data set, combined with a single-cell data set. The clinical, genomic, and metabolic characteristics of patients with low Ki-67 TNBC were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The clinical and pathological characteristics were analyzed in 2217 TNBC patients. Low Ki-67 TNBC was associated with a higher patient age at diagnosis, a lower proportion of invasive ductal carcinoma, increased alterations in the PI3K-AKT-mTOR pathway, upregulated lipid metabolism pathways, and enhanced infiltration of M2 macrophages. High Ki-67 TNBC exhibited a higher prevalence of TP53 gene mutations, elevated nucleotide metabolism, and increased infiltration of M1 macrophages.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We identified specific genomic and metabolic characteristics unique to low Ki-67 TNBC, which have implications for the development of precision therapies and patient stratification strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273089","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":"Role of liquid–liquid phase separation in cancer: Mechanisms and therapeutic implications","authors":"Xuesong Li, Zhuo Yu","doi":"10.1002/cai2.144","DOIUrl":"https://doi.org/10.1002/cai2.144","url":null,"abstract":"<p>Liquid–liquid phase separation (LLPS) has emerged as a pivotal biological phenomenon involved in various cellular processes, including the formation of membrane-less organelles and the regulation of biomolecular condensates through precise spatiotemporal coordination of signaling pathways in cells. Dysregulation of LLPSs results in aberrant biomolecular condensates, which are widely implicated in tumorigenesis and cancer progression. Here, we comprehensively summarize the multifaceted roles of LLPS in tumor biology from the perspective of cancer hallmarks, including genomic stability, metabolic reprogramming progression, ferroptosis, and metastasis, to unveil the intricate mechanisms by which LLPS occurs in tumorigenesis. We discuss current discoveries related to therapeutic involvement and potential clinical applications of LLPS in cancer treatment, highlighting the potential of targeting LLPS-driven processes as novel therapeutic strategies. Additionally, we discuss the challenges associated with new approaches for cancer treatment based on LLPS. This in-depth discussion of the impact of LLPS on fundamental aspects of tumor biology provides new insights into overcoming cancer.</p>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245015","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}
Rui Wang, Ni-sha Wu, Li Wang, Zhi-zhao Zhang, Cheng-fang Wang, Yan Wang, Yan Liang, Yi Zhang, Xiao-wei Qi
{"title":"A pan-cancer analysis of Wnt family member 7B in human cancers","authors":"Rui Wang, Ni-sha Wu, Li Wang, Zhi-zhao Zhang, Cheng-fang Wang, Yan Wang, Yan Liang, Yi Zhang, Xiao-wei Qi","doi":"10.1002/cai2.139","DOIUrl":"https://doi.org/10.1002/cai2.139","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Previous studies have highlighted the crucial role of <i>Wnt7B</i> in the development of various cancers, including breast, pancreatic, and gastric cancers. However, research into the involvement of <i>Wnt7B</i> is often confined to specific tumor types, with a noticeable lack of comprehensive studies spanning multiple cancer forms. The potential of <i>Wnt7B</i> as a diagnostic or prognostic cancer biomarker has not been fully explored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we combined bioinformatics and immunohistochemistry analyses to examine the expression patterns and functions of <i>Wnt7B</i> in cancerous and adjacent noncancerous tissues across a range of tumors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our data indicate that <i>Wnt7B</i> may serve as a novel prognostic biomarker and therapeutic target in certain cancers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We found significant upregulation of <i>Wnt7B</i> expression levels in the majority of cancer cases examined. Furthermore, <i>Wnt7B</i> can influence cancer prognosis by modulating the tumor microenvironment, immune cell infiltration, and tumor stemness, among other factors. Additionally, we examined the associations between anticancer drug sensitivity and <i>Wnt7B</i> expression, which could aid in the development of more precise clinical therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160166","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":"Chinese expert consensus on an innovative patient-centered approach to diagnosis and treatment of cancer","authors":"Hongnan Mo, Ruiqi Zhong, Fei Ma","doi":"10.1002/cai2.137","DOIUrl":"10.1002/cai2.137","url":null,"abstract":"<p>Patient-centered care (PCC) is an innovative approach to the diagnosis and treatment of malignancy that aims to improve patients' experience during the management of their disease. However, despite growing interest, the concept and specifics of PCC remain unclear. This consensus document addresses this gap by providing a literature review and a clear definition of PCC and outlines its main components as observed in real-world practice. These components include daytime diagnostic and treatment procedures, in-hospital and community-based infusion centers, home-based diagnostic and treatment services, smart healthcare solutions, and integration of traditional Chinese medicine. This document delves into the implementation of PCC and explores its potential benefits.</p>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857564","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}
Amirehsan Ghasemi, Soheil Hashtarkhani, David L. Schwartz, Arash Shaban-Nejad
{"title":"Explainable artificial intelligence in breast cancer detection and risk prediction: A systematic scoping review","authors":"Amirehsan Ghasemi, Soheil Hashtarkhani, David L. Schwartz, Arash Shaban-Nejad","doi":"10.1002/cai2.136","DOIUrl":"https://doi.org/10.1002/cai2.136","url":null,"abstract":"<p>With the advances in artificial intelligence (AI), data-driven algorithms are becoming increasingly popular in the medical domain. However, due to the nonlinear and complex behavior of many of these algorithms, decision-making by such algorithms is not trustworthy for clinicians and is considered a black-box process. Hence, the scientific community has introduced explainable artificial intelligence (XAI) to remedy the problem. This systematic scoping review investigates the application of XAI in breast cancer detection and risk prediction. We conducted a comprehensive search on Scopus, IEEE Explore, PubMed, and Google Scholar (first 50 citations) using a systematic search strategy. The search spanned from January 2017 to July 2023, focusing on peer-reviewed studies implementing XAI methods in breast cancer datasets. Thirty studies met our inclusion criteria and were included in the analysis. The results revealed that SHapley Additive exPlanations (SHAP) is the top model-agnostic XAI technique in breast cancer research in terms of usage, explaining the model prediction results, diagnosis and classification of biomarkers, and prognosis and survival analysis. Additionally, the SHAP model primarily explained tree-based ensemble machine learning models. The most common reason is that SHAP is model agnostic, which makes it both popular and useful for explaining any model prediction. Additionally, it is relatively easy to implement effectively and completely suits performant models, such as tree-based models. Explainable AI improves the transparency, interpretability, fairness, and trustworthiness of AI-enabled health systems and medical devices and, ultimately, the quality of care and outcomes.</p>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536862","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}
Xiong Chen, Qinchang Chen, Yuanfang Liu, Ya Qiu, Lin Lv, Zhengtao Zhang, Xuntao Yin, Fangpeng Shu
{"title":"Radiomics models to predict bone marrow metastasis of neuroblastoma using CT","authors":"Xiong Chen, Qinchang Chen, Yuanfang Liu, Ya Qiu, Lin Lv, Zhengtao Zhang, Xuntao Yin, Fangpeng Shu","doi":"10.1002/cai2.135","DOIUrl":"10.1002/cai2.135","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bone marrow is the leading site for metastasis from neuroblastoma and affects the prognosis of patients with neuroblastoma. However, the accurate diagnosis of bone marrow metastasis is limited by the high spatial and temporal heterogeneity of neuroblastoma. Radiomics analysis has been applied in various cancers to build accurate diagnostic models but has not yet been applied to bone marrow metastasis of neuroblastoma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively collected information from 187 patients pathologically diagnosed with neuroblastoma and divided them into training and validation sets in a ratio of 7:3. A total of 2632 radiomics features were retrieved from venous and arterial phases of contrast-enhanced computed tomography (CT), and nine machine learning approaches were used to build radiomics models, including multilayer perceptron (MLP), extreme gradient boosting, and random forest. We also constructed radiomics-clinical models that combined radiomics features with clinical predictors such as age, gender, ascites, and lymph gland metastasis. The performance of the models was evaluated with receiver operating characteristics (ROC) curves, calibration curves, and risk decile plots.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The MLP radiomics model yielded an area under the ROC curve (AUC) of 0.97 (95% confidence interval [CI]: 0.95–0.99) on the training set and 0.90 (95% CI: 0.82–0.95) on the validation set. The radiomics-clinical model using an MLP yielded an AUC of 0.93 (95% CI: 0.89–0.96) on the training set and 0.91 (95% CI: 0.85–0.97) on the validation set.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>MLP-based radiomics and radiomics-clinical models can precisely predict bone marrow metastasis in patients with neuroblastoma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474386","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}
Yihao Wang, Kaixin Yan, Han Duan, Ning Tao, Shaoning Zhu, Yuning Zhang, Yonggang You, Zhen Zhang, Hua Wang, Shunying Hu
{"title":"High-fat-diet-induced obesity promotes simultaneous progression of lung cancer and atherosclerosis in apolipoprotein E-knockout mice","authors":"Yihao Wang, Kaixin Yan, Han Duan, Ning Tao, Shaoning Zhu, Yuning Zhang, Yonggang You, Zhen Zhang, Hua Wang, Shunying Hu","doi":"10.1002/cai2.127","DOIUrl":"https://doi.org/10.1002/cai2.127","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Clinical studies have shown that atherosclerotic cardiovascular disease and cancer often co-exist in the same individual. The present study aimed to investigate the role of high-fat-diet (HFD)-induced obesity in the coexistence of the two diseases and the underlying mechanism in apolipoprotein E-knockout (ApoE<sup>−/−</sup>) mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male ApoE<sup>−/−</sup> mice were fed with a HFD or a normal diet (ND) for 15 weeks. On the first day of Week 13, the mice were inoculated subcutaneously in the right axilla with Lewis lung cancer cells. At Weeks 12 and 15, serum lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and vascular endothelial growth factor levels were measured by enzyme-linked immunosorbent assay, and blood monocytes and macrophages were measured by fluorescence-activated cell sorting. At Week 15, the volume and weight of the local subcutaneous lung cancer and metastatic lung cancer and the amount of aortic atherosclerosis were measured.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At Week 15, compared with mice in the ND group, those in the HFD group had a larger volume of local subcutaneous cancer (<i>p</i> = 0.0004), heavier tumors (<i>p</i> = 0.0235), more metastatic cancer in the lungs (<i>p</i> < 0.0001), a larger area of lung involved in metastatic cancer (<i>p</i> = 0.0031), and larger areas of atherosclerosis in the aorta (<i>p</i> < 0.0001). At Week 12, serum LOX-1, serum vascular endothelial growth factor, and proportions of blood monocytes and macrophages were significantly higher in the HFD group than those in the ND group (<i>p</i> = 0.0002, <i>p</i> = 0.0029, <i>p</i> = 0.0480, and <i>p</i> = 0.0106, respectively); this trend persisted until Week 15 (<i>p</i> = 0.0014, <i>p</i> = 0.0012, <i>p</i> = 0.0001, and <i>p</i> = 0.0204).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this study, HFD-induced obesity could simultaneously promote progression of lung cancer and atherosclerosis in the same mouse. HFD-induced upregulation of LOX-1 may play an important role in the simultaneous progression of these two conditions via the inflammatory response and VEGF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141251465","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":"Efficacy and safety of first-line regimens for advanced HER2-positive breast cancer: A Bayesian network meta-analysis","authors":"Lixi Li, Yun Wu, Bo Lan, Fei Ma","doi":"10.1002/cai2.126","DOIUrl":"https://doi.org/10.1002/cai2.126","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The current standard of care for advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer is pertuzumab plus trastuzumab and docetaxel as first-line therapy. However, with the development of newer treatment regimens, there is a lack of evidence regarding which is the optimal treatment strategy. The aim of this network meta-analysis was to evaluate the efficacy and safety of first-line regimens for advanced HER2-positive breast cancer by indirect comparisons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic review and Bayesian network meta-analysis were conducted. The PubMed, EMBASE, and Cochrane Library databases were searched for relevant articles published through to December 2023. The hazard ratio (HR) and 95% credible interval (CrI) were used to compare progression-free survival (PFS) between treatments, and the odds ratio and 95% CrI were used to compare the objective response rate (ORR) and safety.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty randomized clinical trials that included 15 regimens and 7094 patients were analyzed. Compared with the traditional trastuzumab and docetaxel regimen, PFS was longer on the pyrotinib and trastuzumab plus docetaxel regimen (HR: 0.41, 95% CrI: 0.22–0.75) and the pertuzumab and trastuzumab plus docetaxel regimen (HR: 0.65, 95% CrI: 0.43–0.98). Consistent with the results for PFS, the ORR was better on the pyrotinib and trastuzumab plus docetaxel regimen and the pertuzumab and trastuzumab plus docetaxel regimen than on the traditional trastuzumab and docetaxel regimen. The surface under the cumulative ranking curve indicated that the pyrotinib and trastuzumab plus docetaxel regimen was most likely to rank first in achieving the best PFS and ORR. Comparable results were found for grade ≥3 AE rates of ≥10%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results suggest that the pyrotinib and trastuzumab plus docetaxel regimen is most likely to be the optimal first-line therapy for patients with HER2-positive breast cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141078964","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}
Yuan-yuan Sun, Hai-cheng Gao, Peng Guo, Na Sun, Chan Peng, Zhi-hua Cheng, Jing Gu, Jin-yi Liu, Fei Han
{"title":"Identification of NR3C2 as a functional diagnostic and prognostic biomarker and potential therapeutic target in non-small cell lung cancer","authors":"Yuan-yuan Sun, Hai-cheng Gao, Peng Guo, Na Sun, Chan Peng, Zhi-hua Cheng, Jing Gu, Jin-yi Liu, Fei Han","doi":"10.1002/cai2.122","DOIUrl":"https://doi.org/10.1002/cai2.122","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Non-small cell lung cancer (NSCLC), including the lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) subtypes, is a malignant tumor type with a poor 5-year survival rate. The identification of new powerful diagnostic biomarkers, prognostic biomarkers, and potential therapeutic targets in NSCLC is urgently required.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The UCSC Xena, UALCAN, and GEO databases were used to screen and analyze differentially expressed genes, regulatory modes, and genetic/epigenetic alterations in NSCLC. The UCSC Xena database, GEO database, tissue microarray, and immunohistochemistry staining analyses were used to evaluate the diagnostic and prognostic values. Gain-of-function assays were performed to examine the roles. The ESTIMATE, TIMER, Linked Omics, STRING, and DAVID algorithms were used to analyze potential molecular mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>NR3C2 was identified as a potentially important molecule in NSCLC. NR3C2 is expressed at low levels in NSCLC, LUAD, and LUSC tissues, which is significantly related to the clinical indexes of these patients. Receiver operating characteristic curve analysis suggests that the altered NR3C2 expression patterns have diagnostic value in NSCLC, LUAD, and especially LUSC patients. Decreased NR3C2 expression levels can help predict poor prognosis in NSCLC and LUAD patients but not in LUSC patients. These results have been confirmed both with database analysis and real-world clinical samples on a tissue microarray. Copy number variation contributes to low NR3C2 expression levels in NSCLC and LUAD, while promoter DNA methylation is involved in its downregulation in LUSC. Two NR3C2 promoter methylation sites have high sensitivity and specificity for LUSC diagnosis with clinical application potential. NR3C2 may be a key participant in NSCLC development and progression and is closely associated with the tumor microenvironment and immune cell infiltration. NR3C2 co-expressed genes are involved in many cancer-related signaling pathways, further supporting a potentially significant role of NR3C2 in NSCLC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>NR3C2 is a novel potential diagnostic and prognostic biomarker and therapeutic target in NSCLC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141073706","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":"Integrative analyses identified gap junction beta-2 as a prognostic biomarker and therapeutic target for breast cancer","authors":"Di Zhang, Lixi Li, Fei Ma","doi":"10.1002/cai2.128","DOIUrl":"https://doi.org/10.1002/cai2.128","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Increasing evidence has shown that connexins are involved in the regulation of tumor development, immune escape, and drug resistance. This study investigated the gene expression patterns, prognostic values, and potential mechanisms of connexins in breast cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a comprehensive analysis of connexins using public gene and protein expression databases and clinical samples from our institution. Connexin mRNA expressions in breast cancer and matched normal tissues were compared, and multiomics studies were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Gap junction beta-2 mRNA was overexpressed in breast cancers of different pathological types and molecular subtypes, and its high expression was associated with poor prognosis. The tumor membrane of the gap junction beta-2 mutated group was positive, and the corresponding protein was expressed. Somatic mutation and copy number variation of gap junction beta-2 are rare in breast cancer. The gap junction beta-2 transcription level in the p110α subunit of the phosphoinositide 3-kinase mutant subgroup was higher than that in the wild-type subgroup. Gap junction beta-2 was associated with the phosphoinositide 3-kinase-Akt signaling pathway, extracellular matrix–receptor interaction, focal adhesion, and proteoglycans in cancer. Furthermore, gap junction beta-2 overexpression may be associated with phosphoinositide 3-kinase and histone deacetylase inhibitor resistance, and its expression level correlated with infiltrating CD8+ T cells, macrophages, neutrophils, and dendritic cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Gap junction beta-2 may be a promising therapeutic target for targeted therapy and immunotherapy and may be used to predict breast cancer prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069113","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}