Zhengxing Li, Yuewen Hu, Chang Xu, Zixiu Zou, Zhenyu Sun, Zhunyi Gao, Man Xiao, Shicheng Guo, Yi Wang, Haijian Wang, Zhiping Wang, Qiang Li, Bo Shen, Yuanlin Song, Junjie Wu
{"title":"Prognostic Significance of <i>Methyl-CpG Binding Domain4</i> Polymorphism rs140693 and Clinical Characteristics in Chinese Lung Cancer Patients.","authors":"Zhengxing Li, Yuewen Hu, Chang Xu, Zixiu Zou, Zhenyu Sun, Zhunyi Gao, Man Xiao, Shicheng Guo, Yi Wang, Haijian Wang, Zhiping Wang, Qiang Li, Bo Shen, Yuanlin Song, Junjie Wu","doi":"10.1007/s43657-024-00171-z","DOIUrl":"10.1007/s43657-024-00171-z","url":null,"abstract":"<p><p>Lung cancer remains the leading cause of death among cancer patients, and the five-year survival rate is less than 25%. However, <i>Methyl-CpG Binding Domain</i> (<i>MBD</i>)<i>4</i> polymorphism rs140693 predicts the prognosis of lung cancer patients still needs further verification. Primary lung cancer patients (<i>n</i> = 839) were collected from two hospitals, genomic DNA was extracted from blood, and genotyping was performed using SNPcan technology. Kaplan-Meier technique and multivariate Cox proportional hazards model were used to analyze the prognosis association between <i>MBD4</i> and clinical characteristics. Significantly conferred a poorer prognosis was associated with the CT genotype (CT vs. CC; adjusted hazard ratio [HR] = 1.21, 95% CI: 1.03-1.43, <i>p</i> = 0.023) and dominant CT + TT genotype (CT + TT vs. CC; HR = 1.19, 95% CI: 1.02-1.39, <i>p</i> = 0.029) of <i>MBD4</i> polymorphism rs140693 for all lung cancer patients, compared with the CC genotype. Stratified analysis showed that polymorphism rs140693 CT and dominant CT + TT genotype conferred a significantly poorer prognosis in female and lung adenocarcinoma (ADC) cancer patients, compared with the CC genotype. Non-small cell lung cancer (NSCLC) patients with the CT genotype had a poorer prognosis than those with the CC genotype. Additionally, the allele T of small cell lung cancer (SCLC) patients compared with the allele C was associated with a poor prognosis, and the CT and recessive TT genotype of SCLC patients conferred a significantly poor prognosis. The <i>MBD4</i> polymorphism rs140693 is a significant prognostic genetic marker for predicting the prognosis of lung cancer patients.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-024-00171-z.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"4 5","pages":"453-464"},"PeriodicalIF":3.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901008","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":"Unveiling Metabolic Signatures in Osteoarthritis Progression through Non-Targeted Metabolomics Analysis: A Paradigm Shift in Diagnosis and Treatment Prospects.","authors":"Peng Wu","doi":"10.1007/s43657-024-00177-7","DOIUrl":"10.1007/s43657-024-00177-7","url":null,"abstract":"","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"4 5","pages":"525-526"},"PeriodicalIF":3.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901010","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":"Senescence-Related LncRNAs: Pioneering Indicators for Ovarian Cancer Outcomes.","authors":"Shao-Bei Fan, Xiao-Feng Xie, Wang Wei, Tian Hua","doi":"10.1007/s43657-024-00163-z","DOIUrl":"10.1007/s43657-024-00163-z","url":null,"abstract":"<p><p>In gynecological oncology, ovarian cancer (OC) remains the most lethal, highlighting its significance in public health. Our research focused on the role of long non-coding RNA (lncRNA) in OC, particularly senescence-related lncRNAs (SnRlncRNAs), crucial for OC prognosis. Utilizing data from the genotype-tissue expression (GTEx) and cancer genome Atlas (TCGA), SnRlncRNAs were discerned and subsequently, a risk signature was sculpted using co-expression and differential expression analyses, Cox regression, and least absolute shrinkage and selection operator (LASSO). This signature's robustness was validated through time-dependent receiver operating characteristics (ROC), and multivariate Cox regression, with further validation in the international cancer genome consortium (ICGC). Gene set enrichment analyses (GSEA) unveiled pathways intertwined with risk groups. The ROC, alongside the nomogram and calibration outcomes, attested to the model's robust predictive accuracy. Of particular significance, our model has demonstrated superiority over several commonly utilized clinical indicators, such as stage and grade. Patients in the low-risk group demonstrated greater immune infiltration and varied drug sensitivities compared to other groups. Moreover, consensus clustering classified OC patients into four distinct groups based on the expression of 17 SnRlncRNAs, showing diverse survival rates. In conclusion, these findings underscored the robustness and reliability of our model and highlighted its potential for facilitating improved decision-making in the context of risk assessment, and demonstrated that these markers potentially served as robust, efficacious biomarkers and prognostic tools, offering insights into predicting OC response to anticancer therapeutics.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-024-00163-z.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"4 4","pages":"379-393"},"PeriodicalIF":3.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712072","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":"No Association of Polycystic Ovary Syndrome with Pancreatic Cancer: A Mendelian Randomization Study.","authors":"Xueying Gao, Yuteng Wang, Yikun Wang, Ziyi Yang, Xueqi Yan, Shumin Li, Yonghui Jiang, Yimeng Li, Shigang Zhao, Han Zhao, Zi-Jiang Chen","doi":"10.1007/s43657-024-00156-y","DOIUrl":"10.1007/s43657-024-00156-y","url":null,"abstract":"<p><p>Recently, there has been a debate regarding the association between polycystic ovary syndrome (PCOS) and pancreatic cancer (PC). In order to examine the causal relationship between PCOS and PC, we conducted a Mendelian randomization study, which utilized 12 single nucleotide polymorphisms (SNPs) identified from a genome-wide association study (GWAS) meta-analysis that included 10,074 PCOS cases and 103,164 controls of European ancestry as instrumental variables (IVs). The outcome data were obtained from the FinnGen database (including 605 cases and 218,187 controls). We demonstrate that genetically predicted PCOS is not causally associated with PC risk in Europeans (odds ratio = 0.99, 95% confidence interval (CI) = 0.72-1.36, <i>p</i> > 0.05). Sensitivity analysis showed horizontal pleiotropy (intercept <i>p</i> > 0.05), heterogeneity (Cochran Q <i>p</i> > 0.05), and the leave-one-out sensitivity test showed that individual SNP effects had no influence on the results. In conclusion, our study did not provide evidence of a causal link between PCOS and PC.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-024-00156-y.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"4 5","pages":"522-524"},"PeriodicalIF":3.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900995","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":"Investigation on Phenomics of Traditional Chinese Medicine from the Diabetes.","authors":"Boxun Zhang, Lijuan Zhou, Keyu Chen, Xinyi Fang, Qingwei Li, Zezheng Gao, Fengmei Lian, Min Li, Jiaxing Tian, Linhua Zhao, Xiaolin Tong","doi":"10.1007/s43657-023-00146-6","DOIUrl":"https://doi.org/10.1007/s43657-023-00146-6","url":null,"abstract":"<p><p>With thousands of years of application history, traditional Chinese medicine (TCM) has unique advantages in the prevention of various chronic diseases, and in recent years, the development of TCM has presented a situation where opportunities and challenges coexist. Phenomics is an emerging area of life science research, which has numerous similarities to the cognitive perspective of TCM. Thus, how to carry out the interdisciplinary research between TCM and phenomics deserves in-depth discussion. Diabetes is one of the most common chronic non-communicable diseases around the world, and TCM plays an important role in all stages of diabetes treatment, but the molecular mechanisms are difficult to elucidate. Phenomics research can not only reveal the hidden scientific connotations of TCM, but also provide a bridge for the confluence and complementary between TCM and Western medicine. Facing the challenges of the TCM phenomics research, we suggest applying the State-target theory (STT) to overall plan relevant researches, namely, focusing on the disease development, change trends, and core targets of each stage, and to deepen the understanding of TCM disease phenotypes and the therapeutic mechanisms of herbal medicine.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-023-00146-6.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"4 3","pages":"257-268"},"PeriodicalIF":3.7,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482569","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}
Chengyan Wang, Shuo Wang, Sha Hua, Ruokun Li, Yan Li, Zhang Shi, Kai Feng, Lizhen Lan, Meng Liu, Xutong Kuang, Xueqin Xia, Shihai Zhao, Xiaodan Ye, Jianhua Jin, Jing Li, Bin Yang, Ming-Hua Zheng, Weibo Chen, Ying-Hua Chu, Juan Hu, Xiahai Zhuang, Xiaolong Qi, Wenjia Bai, He Wang, Jingchun Luo, Mei Tian
{"title":"A Protocol for Body MRI/CT and Extraction of Imaging-Derived Phenotypes (IDPs) from the China Phenobank Project.","authors":"Chengyan Wang, Shuo Wang, Sha Hua, Ruokun Li, Yan Li, Zhang Shi, Kai Feng, Lizhen Lan, Meng Liu, Xutong Kuang, Xueqin Xia, Shihai Zhao, Xiaodan Ye, Jianhua Jin, Jing Li, Bin Yang, Ming-Hua Zheng, Weibo Chen, Ying-Hua Chu, Juan Hu, Xiahai Zhuang, Xiaolong Qi, Wenjia Bai, He Wang, Jingchun Luo, Mei Tian","doi":"10.1007/s43657-023-00141-x","DOIUrl":"10.1007/s43657-023-00141-x","url":null,"abstract":"<p><p>Currently, standard protocols for body imaging and corresponding image processing pipelines in population-based cohort studies are unavailable, limiting the applications of body imaging. Based on the China Phenobank Project (CHPP), the present study described a body imaging protocol for multiple organs, including cardiac structures, liver, spleen, pancreas, kidneys, lung, prostate, and uterus, and the corresponding image processing pipelines promoted its development. Briefly, the body imaging protocol comprised a 40-min cardiac magnetic resonance imaging (MRI) scan, a 5-min computed tomography (CT) scan, a 20-min abdominal MRI scan, and a 10-min pelvic MRI scan. The recommended image processing pipeline utilized deep learning segmentation models to facilitate the analysis of large amount of data. This study aimed to provide a reference for planning studies based on the CHPP platform.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"4 6","pages":"594-616"},"PeriodicalIF":3.7,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588510","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}
Ying Sun, Haijing Ma, Xiaolan Zhou, Leihuan Huang, Peng Yu, Yun Qi, Gang Wei, Ting Ni
{"title":"Deficiency of Gut-Enriched Lipase H Promotes Gut Aging and Reduces Lifespan in <i>Drosophila</i>.","authors":"Ying Sun, Haijing Ma, Xiaolan Zhou, Leihuan Huang, Peng Yu, Yun Qi, Gang Wei, Ting Ni","doi":"10.1007/s43657-024-00187-5","DOIUrl":"10.1007/s43657-024-00187-5","url":null,"abstract":"<p><p><i>Liph</i>, a gut-enriched Lipase H encoding gene, shows decreased expression during gut aging in both fruit fly and mouse. However, whether such evolutionary conserved <i>Liph</i> plays a protective role in gut aging remains unknown. Here we report that knocking down <i>CG6295</i>, the <i>Drosophila</i> ortholog of the mammalian <i>Liph</i>, led to a shortened lifespan. Loss of <i>CG6295</i> in adult fly whole body caused impaired gut integrity and function, as well as reduced gut lipid storage in <i>Drosophila</i>. Activation of the Toll/ immune deficiency (Imd) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) immune pathways, and the release of pro-inflammatory cytokine Upd3 (IL-6) indicated immune responses in <i>CG6295</i> knockdown samples. What's more, knockdown of <i>Drosophila CG6295</i> specifically in enterocytes (ECs) led to enlarged and flattened ECs, suggesting a potential regulatory mechanism of <i>CG6295</i> in gut aging. In addition, down-regulation of <i>Liph</i> induced senescence-associated cellular and molecular phenotypes in a rat intestine cell model, suggesting the evolutionary conserved role of <i>Liph</i> in gut aging. Together, we discovered <i>Liph</i> as a novel regulator for gut aging.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-024-00187-5.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"4 6","pages":"531-547"},"PeriodicalIF":3.7,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588518","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}
Shuang Zhao, Zhongling Luo, Ying Wang, Xinghua Gao, Juan Tao, Yong Cui, Aijun Chen, Daxing Cai, Yan Ding, Heng Gu, Jianying Gu, Chao Ji, Xiaojing Kang, Qianjin Lu, Chengzhi Lv, Min Li, Wei Li, Wei Liu, Xia Li, Yuzhen Li, Xiaoyong Man, Jianjun Qiao, Liangdan Sun, Yuling Shi, Wenyu Wu, Jianxin Xia, Rong Xiao, Bin Yang, Yehong Kuang, Zeyu Chen, Jingyue Fang, Jian Kang, Minghui Yang, Mi Zhang, Juan Su, Xuejun Zhang, Xiang Chen
{"title":"Expert Consensus on Big Data Collection of Skin and Appendage Disease Phenotypes in Chinese.","authors":"Shuang Zhao, Zhongling Luo, Ying Wang, Xinghua Gao, Juan Tao, Yong Cui, Aijun Chen, Daxing Cai, Yan Ding, Heng Gu, Jianying Gu, Chao Ji, Xiaojing Kang, Qianjin Lu, Chengzhi Lv, Min Li, Wei Li, Wei Liu, Xia Li, Yuzhen Li, Xiaoyong Man, Jianjun Qiao, Liangdan Sun, Yuling Shi, Wenyu Wu, Jianxin Xia, Rong Xiao, Bin Yang, Yehong Kuang, Zeyu Chen, Jingyue Fang, Jian Kang, Minghui Yang, Mi Zhang, Juan Su, Xuejun Zhang, Xiang Chen","doi":"10.1007/s43657-023-00142-w","DOIUrl":"https://doi.org/10.1007/s43657-023-00142-w","url":null,"abstract":"<p><p>The collection of big data on skin and appendage phenotypes has revolutionized the field of personalized diagnosis and treatment by enabling the evaluation of individual characteristics and early detection of abnormalities. To establish a standardized system for collecting and measuring big data on phenotypes, a systematic categorization of measurement entries has been undertaken, accompanied by recommendations on measurement entries, environmental equipment requirements, and collection processes, tailored to the needs of different usage scenarios. Specific collection sites have also been recommended based on different index characteristics. A multi-center, multi-regional collaboration has been initiated to collect big date on phenotypes of healthy and diseased skin in the Chinese population. This data will be correlated with patient disease information, exploring the factors influencing skin phenotype, analyzing the phenotypic data features that can predict prognosis, and ultimately promoting the exploration of the pathophysiology and pathogenesis of skin diseases and therapeutic approaches. Non-invasive skin measurement robots are also in development. This consensus aims to provide a reference for the study of phenomics and the standardization of phenotypic measurements of skin and appendages in China.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"4 3","pages":"269-292"},"PeriodicalIF":3.7,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482568","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}
Huazhen Yang, Can Hou, Wenwen Chen, Yu Zeng, Yuanyuan Qu, Yajing Sun, Yao Hu, Xiangdong Tang, Huan Song
{"title":"Disease Modules Associated with Unfavorable Sleep Patterns and Their Genetic Determinants: A Prospective Cohort Study of the UK Biobank.","authors":"Huazhen Yang, Can Hou, Wenwen Chen, Yu Zeng, Yuanyuan Qu, Yajing Sun, Yao Hu, Xiangdong Tang, Huan Song","doi":"10.1007/s43657-023-00144-8","DOIUrl":"10.1007/s43657-023-00144-8","url":null,"abstract":"<p><p>Despite the established associations between sleep-related traits and major diseases, comprehensive assessment on affected disease modules and their genetic determinants is lacking. Using multiple correspondence analysis and the k-means clustering algorithm, 235,826 eligible participants were clustered into distinct unfavorable sleep patterns [short sleep duration (<i>n</i> = 10,073), snoring (22,419), insomnia (102,771), insomnia and snoring (62,909)] and favorable sleep pattern groups (37,654). The associations of unfavorable sleep patterns with 134 diseases were estimated using Cox regression models; and comorbidity network analyses were applied for disease module identification. Genetic determinants associated with each disease module were identified by genome-wide association studies (GWAS). During an average follow-up of 10.80 years, unfavorable sleep patterns featured by 'short sleep duration', 'snoring', 'insomnia', and 'insomnia and snoring' were associated with increased risk of 0, 9, 10, and 19 diseases, respectively. Furthermore, comorbidity network analyses categorized these affected diseases into three disease modules, characterized by predominant diseases related to digestive system, circulatory and endocrine systems (snoring-related patterns only), and musculoskeletal system (insomnia-related patterns only). Using the number of affected diseases, as an index of a person's susceptibility to each disease module [i.e., susceptible score (SS)], GWAS analyses identified five, one, and three significant loci associated with the residual SS of these aforementioned disease modules, respectively, which mapped to several potential biological pathways, including those related to hormone regulation and catecholamine uptake. In conclusion, individuals with unfavorable sleep patterns, particularly snoring and insomnia, had increased risk of multiple diseases. The identification of three major disease modules with their relevant genetic determinants may facilitate strategy development for precision prevention of future health decline.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-023-00144-8.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"4 5","pages":"415-429"},"PeriodicalIF":3.7,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900989","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}
Xin-Qiang Wu, Zhi Shang, Cui Xiong, Wen-Hao Xu, Bo Dai, Yu-Ling Chen, Yu-Yang Feng, Yue Wang, Jia-Qi Su, Jian-Yuan Zhao, Hai-Liang Zhang, Yan Shi, Yuan-Yuan Qu, Ding-Wei Ye
{"title":"Dissecting the Implications of Calumenin in Malignancy and Heterogeneity of the Microenvironment of Clear Cell Renal Cell Carcinoma Using Multi-Omics Data.","authors":"Xin-Qiang Wu, Zhi Shang, Cui Xiong, Wen-Hao Xu, Bo Dai, Yu-Ling Chen, Yu-Yang Feng, Yue Wang, Jia-Qi Su, Jian-Yuan Zhao, Hai-Liang Zhang, Yan Shi, Yuan-Yuan Qu, Ding-Wei Ye","doi":"10.1007/s43657-024-00169-7","DOIUrl":"10.1007/s43657-024-00169-7","url":null,"abstract":"<p><p>Increasing evidence indicates that Calumenin (CALU), which is localized in the endoplasmic reticulum, is significantly associated with tumor progression. However, the effect of CALU on patients with clear cell renal cell carcinoma (ccRCC) is unknown. By integrating multi-omics data and molecular biology experiments, we found that CALU expression was significantly increased in tumors compared with normal tissues, and the pathological grade and prognosis of patients were correlated with CALU expression. Next, knockdown or ectopic expression of CALU could affect the proliferative and invasive abilities of ccRCC cells. Moreover, immune landscape characterization revealed that CALU expression was positively associated with neutrophils and macrophages, whereas it was negatively associated with natural killer T cells and CD8<sup>+</sup> T cells. Single-cell sequencing showed that the localization and binding targets of CALU mainly involved monocytes/macrophages and CD4<sup>+</sup> and CD8<sup>+</sup> T-cells. Sensitivity analysis of common chemotherapeutic drugs showed that high expression of CALU could sensitize chemotherapeutic drugs such as 5Z-7-Oxozeaenol, AMG-706 and Cytarabine, but could lead to drug resistance to chemotherapeutic drugs such as Embelin, Salubrinal and Tipifarnib. We demonstrated a significant correlation between high CALU expression and poor patient survival. Further, we demonstrated a correlation between CALU expression, tumor microenvironment, and the sensitivity of patients to common chemo- and immuno-therapy drugs. Thus, our results indicate that CALU could be a biomarker and designing personalized treatment approaches for ccRCC patients.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-024-00169-7.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"4 4","pages":"365-378"},"PeriodicalIF":3.7,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712023","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}