International Journal of Cancer最新文献

{"title":"Untangling heterogeneity: From complexity to prediction","authors":"Ian G. Mills","doi":"10.1002/ijc.34709","DOIUrl":"10.1002/ijc.34709","url":null,"abstract":"<p>Prostate cancer is a high-incidence male cancer that progresses to metastatic disease in a subset of diagnosed cases. Early detection of high-risk disease is a key translational challenge and if successful will reduce overtreatment while potentially improving the outcomes for those patients most in need of early interventions. There are many challenges that need to be surmounted to achieve this translational outcome, not least the fact that prostate cancer is a multi-focal disease. Multi-focality is observed in the often-diverse histopathology of the disease in a single patient, as well as in the mutational and transcriptional heterogeneity in sequencing data from selected multi-site cores.<span><sup>1</sup></span> In this study, Salachan et al. use spatial transcriptomics on samples from patients with castrate-resistant (CRPC) and neuroendocrine prostate cancer (NEPC), poor-prognosis treatment-resistant prostate cancers.<span><sup>2</sup></span> By deriving a signature associated with an immune-dysregulated malignant niches or ‘ecosystem’, they are able to prognosticate larger publicly available cohorts for which bulk sequencing data are available.</p><p>The chosen platform for this study was Visium (10x Genomics) and the work was undertaken on fresh-frozen tissue samples. The technology as applied here provides a spot-level resolution of 10 to 15 cells and coverage of a fraction of the cellular transcriptome per spot. The cellular and transcriptomic resolution of spatial platforms is improving all the time and this study represents an early window into these niches. Undoubtedly, our ability to discriminate between the contributions of distinct cells and cell types to spatial transcriptomic profiles will improve. New computational methods to de-convolute these data according to cell type and spatial location are also being rapidly developed. In this study, Spatial Cellular Estimator for Tumours (SpaCET) was used to infer cellular identities within the ST data.<span><sup>3</sup></span> As well as determining local cell densities and the fractions of cells of different types within the spot-level data, this method also uses ligand-receptor co-expression analysis to infer intercellular interactions between different cell types.<span><sup>3</sup></span> This represents one approach amongst many being developed to make spatial data biologically interpretable, and particularly in deciphering cross-talk/cellular co-dependencies that may permit niches to emerge and survive within tissue samples. In deriving signatures, the authors have focused on histo-pathologically malignant regions of tissue within the three samples selected. SpaCET distinguishes between malignant cells and other cell types by comparing spatial transcriptomic data initially to curated cancer-type specific dictionary gene patterns reflecting copy-number alteration or malignant gene expression signatures. The intent is to be able to identify malignant cell populations that have both","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"153 12","pages":"1940-1941"},"PeriodicalIF":6.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.34709","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10484326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial whole transcriptome profiling of primary tumor from patients with metastatic prostate cancer","authors":"Paul Vinu Salachan,&nbsp;Martin Rasmussen,&nbsp;Benedicte Parm Ulhøi,&nbsp;Jørgen Bjerggaard Jensen,&nbsp;Michael Borre,&nbsp;Karina Dalsgaard Sørensen","doi":"10.1002/ijc.34708","DOIUrl":"10.1002/ijc.34708","url":null,"abstract":"<p>Prostate cancer (PCa) is a highly heterogeneous disease in terms of its molecular makeup and clinical prognosis. The prostate tumor microenvironment (TME) is hypothesized to play an important role in driving disease aggressiveness, but precise mechanisms remain elusive. In our study, we used spatial transcriptomics to explore for the first time the spatial gene expression heterogeneity within primary prostate tumors from patients with metastatic disease. In total, we analyzed 5459 tissue spots from three PCa patients comprising castration-resistant (CRPC) and neuroendocrine (NEPC) disease stages. Within CRPC, we identified a T cell cluster whose activity might be impaired by nearby regulatory T cells, potentially mediating the aggressive disease phenotype. Moreover, we identified Hallmark signatures of epithelial-mesenchymal transition in a cancer-associated fibroblast (CAF) cluster, indicating the aggressive characteristic of the primary TME leading to metastatic dissemination. Within NEPC, we identified active immune-stroma cross-talk exemplified by significant ligand-receptor interactions between CAFs and M2 macrophages. Further, we identified a malignant cell population that was associated with the down-regulation of an immune-related gene signature. Lower expression of this signature was associated with higher levels of genomic instability in advanced PCa patients (SU2C cohort, n = 99) and poor recurrence free survival in early-stage PCa patients (TCGA cohort, n = 395), suggesting prognostic biomarker potential. Taken together, our study reveals the importance of whole transcriptome profiling at spatial resolution for biomarker discovery and for advancing our understanding of tumor biology.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"153 12","pages":"2055-2067"},"PeriodicalIF":6.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.34708","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10130470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Universal test and treat in Cameroon: a comparative retrospective analysis of mortality and loss to follow-up before and after a strategic change in approach to HIV care.","authors":"Cavin Epie Bekolo, Sylvester Atanga Ndeso, Linda Lucienne Moifo, Nkwele Mangala, Tatiana Danielle Yimdjo, Jerome Ateudjieu, Charles Kouanfack, Alain Djam, Earnest Njih Tabah, Solange Whegang, Clarisse Mapa-Tassou, Nicolas Tendongfor, Dickson Shey Nsagha, Siméon-Pierre Choukem","doi":"10.11604/pamj.2023.45.191.40448","DOIUrl":"10.11604/pamj.2023.45.191.40448","url":null,"abstract":"<p><strong>Introduction: </strong>an increasing number of persons living with HIV (PLHIV) are accessing antiretroviral therapy (ART) since the adoption of the universal test and treat (UTT) policy by Cameroon in 2016. We sought to evaluate the effectiveness of the UTT approach to keep this growing number of PLHIV on a lifelong treatment.</p><p><strong>Methods: </strong>a retrospective cohort analysis was conducted at the Nkongsamba Regional Hospital between 2002 and 2020, using routine data to compare the cumulative incidence of loss to follow-up (LTFU) and mortality between PLHIV initiated on ART under UTT guidelines and those initiated under the standard deferred approach. Chi-squared test was used to compare the risk of attrition between the guideline periods while multiple logistic regression modelling was used to adjust for confounders.</p><p><strong>Results: </strong>of 1627 PLHIV included for analysis, 756 (46.47%) were enrolled during the era of UTT with 545 (33.54%) initiated on ART on the same day of HIV diagnosis. The transition to the UTT era was associated with an overall reduction in the risk of LTFU by 73% (aOR = 0.27, 95%CI: 0.17 - 0.45). There was modest evidence that the odds of mortality had increased under the UTT policy by about 3-fold (aOR = 2.86, 95%CI: 0.91-8.94). Same-day initiation had no overall effect on LTFU or mortality. LTFU was lower among the same-day initiators in the first 24 months but increased thereafter above the rate among late initiators.</p><p><strong>Conclusion: </strong>overall ART programme implementation under the UTT has led to a significant decline in LTFU though mortality appeared to have increased. Ongoing efforts to keep patients on long-term treatment should be sustained while other innovative schemes are sought.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"98 1","pages":"191"},"PeriodicalIF":0.9,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10656581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73200109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide exploration of genetic interactions for bladder cancer risk","authors":"Evan Yi-Wen Yu,&nbsp;Qiu-Yi Tang,&nbsp;Ya-Ting Chen,&nbsp;Yan-Xi Zhang,&nbsp;Ya-Nan Dai,&nbsp;Yu-Xuan Wu,&nbsp;Wen-Chao Li,&nbsp;Siamak Mehrkanoon,&nbsp;Shi-Zhi Wang,&nbsp;Maurice P. Zeegers,&nbsp;Anke Wesselius","doi":"10.1002/ijc.34690","DOIUrl":"10.1002/ijc.34690","url":null,"abstract":"<p>Although GWASs have been conducted to investigate genetic variation of bladder tumorigenesis, little is known about genetic interactions that may influence bladder cancer (BC) risk. By leveraging large-scale participants from UK Biobank, we established a discovery database with 4000 Caucasian participants (2000 cases vs 2000 non-cases), a database with 1648 Caucasian participants (824 cases vs 824 non-cases) and 856 non-Caucasian participants (428 cases vs 428 non-cases) as validation. We then performed a genome-wide SNP-SNP interaction investigation related to BC risk based a machine learning approach (ie, GenEpi). Moreover, we used the selected interactions to build a BC screening model with an integrated interaction-empowered polygenic risk score (iPRS) based on Cox proportional hazard model. With Bonferroni correction, we identified 10 statistically significant pairs of SNPs, which located in 17 chromosomes. Of these, four SNP-SNP interactions were found to be positively associated with BC risk among Caucasian participants (ORs 1.57-2.03), while six SNP-SNP interactions showed negatively associated with BC risk (ORs 0.54-0.65). Only four of the SNP-SNP interactions were consistently identified in non-Caucasian participants located in <i>ST7L</i>-<i>ADSS2, FHIT</i>-<i>CHDH, LARP4B</i>-<i>LHPP</i> and <i>RBFOX3</i>-<i>MPRIP</i>. In addition, the iPRS showed a HR of 1.81 (95% CI: 1.46-2.09) compared the highest tertile to the lowest tertile, with an enhanced AUC (0.91; 95% CI:0.85-0.97) than PRS (AUC: 0.86; 95% CI:0.76-0.95; <i>P</i>-_{DeLong test} = 2.2 × 10⁻⁴). In summary, this study identified several important SNP-SNP interactions for BC risk, and developed an iPRS model for BC screening, which may help to identify the people at high-risk state of BC before early manifestation.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"154 1","pages":"81-93"},"PeriodicalIF":6.4,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.34690","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10084988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance of the HPV E6/E7 mRNA Aptima HPV assay combined with partial genotyping compared with the HPV DNA Cobas 4800 HPV test for use in primary screening: Results from the CERVIVA HPV primary screening study in Ireland","authors":"Christine White,&nbsp;Stephen Reynolds,&nbsp;Katherine Murphy,&nbsp;Helen Keegan,&nbsp;Padma Naik,&nbsp;Roisin O'Brien,&nbsp;Loretto Pilkington,&nbsp;Imogen Sharkey Ochoa,&nbsp;Grainne Glesson,&nbsp;Noirin Russell,&nbsp;David Nuttall,&nbsp;Prerna Tewari,&nbsp;Fiona Wright,&nbsp;Sharon O'Toole,&nbsp;Linda Sharp,&nbsp;Grainne Flannelly,&nbsp;John J. O'Leary,&nbsp;Cara M. Martin,&nbsp;CERVIVA the Irish Cervical Screening Research Consortium","doi":"10.1002/ijc.34685","DOIUrl":"10.1002/ijc.34685","url":null,"abstract":"<p>There are currently several validated HPV tests. However, longitudinal data which spans appropriate age ranges, as well as evaluation of potential screening algorithms are necessary for screening programmes choice of test. The objective of our study was to evaluate the performance of HPV mRNA and HPV DNA testing, including partial genotyping, in routine cervical screening. As part of the CERVIVA HPV Primary Screening Study, ThinPrep samples from 10 150 women were tested for HPV mRNA using the Aptima HPV assay and HPV DNA using the Cobas 4800 HPV test. HPV mRNA-positive women were further assessed with the Aptima genotyping assay for HPV 16/18/45. Baseline cytology and prospective follow-up data were collected. The performance of the two tests was examined over 42 months (to date). HPV mRNA demonstrated equivalent sensitivity to HPV DNA testing for detection of CIN2+ (93.2% [92.4-93.9] vs 92.8% [92.0-93.6], respectively) and CIN3+ (94.6% [93.8-95.3] vs 94.6% [93.8-95.3]). HPV mRNA testing had significantly higher specificity compared to HPV DNA for detection of CIN2+ (84.0% [83.5-84.5] vs 80.8% [80.2-81.4], respectively) and CIN3+ (88.44% [88.2-88.6] vs 85.62 [85.4-85.9]). The proportion of CIN2+ and CIN3+, over 3 years (42 months), in HPV-negative women was comparable for both RNA (0.20% and 0.10%) and DNA (0.22% and 0.11%). Genotyping data was comparable across both assay platforms. In the context of HPV primary screening HPV mRNA testing has potential to reduce triage tests and follow-up tests at 12 months compared to DNA testing, with no significant difference in detection of CIN2+ and CIN3+.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"154 1","pages":"53-64"},"PeriodicalIF":6.4,"publicationDate":"2023-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.34685","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10076871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Testicular germ cell tumour cells release microRNA-containing extracellular vesicles that induce phenotypic and genotypic changes in cells of the tumour microenvironment","authors":"Luz Alonso-Crisostomo,&nbsp;Jennifer Trendell,&nbsp;Marta Ferraresso,&nbsp;Shivani Bailey,&nbsp;Dawn Ward,&nbsp;Zachary G. L. Scurlock,&nbsp;Stephanie C. Wenlock,&nbsp;Carlos A. P. Bastos,&nbsp;Ravin Jugdaohsingh,&nbsp;Nuno J. Faria,&nbsp;Anton J. Enright,&nbsp;Cinzia G. Scarpini,&nbsp;Nicholas Coleman,&nbsp;Matthew J. Murray","doi":"10.1002/ijc.34697","DOIUrl":"10.1002/ijc.34697","url":null,"abstract":"<p>Malignant germ-cell-tumours (GCTs) are characterised by microRNA (miRNA/miR-) dysregulation, with universal over-expression of miR-371~373 and miR-302/367 clusters regardless of patient age, tumour site, or subtype (seminoma/yolk-sac-tumour/embryonal carcinoma). These miRNAs are released into the bloodstream, presumed within extracellular-vesicles (EVs) and represent promising biomarkers. Here, we comprehensively examined the role of EVs, and their miRNA cargo, on (fibroblast/endothelial/macrophage) cells representative of the testicular GCT (TGCT) tumour microenvironment (TME). Small RNA next-generation-sequencing was performed on 34 samples, comprising representative malignant GCT cell lines/EVs and controls (testis fibroblast [Hs1.Tes] cell-line/EVs and testis/ovary samples). TME cells received TGCT co-culture, TGCT-derived EVs, and a miRNA overexpression system (miR-371a-OE) to assess functional relevance. TGCT cells secreted EVs into culture media. MiR-371~373 and miR-302/367 cluster miRNAs were overexpressed in all TGCT cells/subtypes compared with control cells and were highly abundant in TGCT-derived EVs, with miR-371a-3p/miR-371a-5p the most abundant. TGCT co-culture resulted in increased levels of miRNAs from the miR-371~373 and miR-302/367 clusters in TME (fibroblast) cells. Next, fluorescent labelling demonstrated TGCT-derived EVs were internalised by all TME (fibroblast/endothelial/macrophage) cells. TME (fibroblast/endothelial) cell treatment with EVs derived from different TGCT subtypes resulted in increased miR-371~373 and miR-302/367 miRNA levels, and other generic (eg, miR-205-5p/miR-148-3p) and subtype-specific (seminoma, eg, miR-203a-3p; yolk-sac-tumour, eg, miR-375-3p) miRNAs. MiR-371a-OE in TME cells resulted in increased collagen contraction (fibroblasts) and angiogenesis (endothelial cells), via direct mRNA downregulation and alteration of relevant pathways. TGCT cells communicate with nontumour stromal TME cells through release of EVs enriched in oncogenic miRNAs, potentially contributing to tumour progression.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"154 2","pages":"372-388"},"PeriodicalIF":6.4,"publicationDate":"2023-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.34697","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10070350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microfluidic droplet encapsulation-guided organoid growth promotes parental tumor phenotype recapitulation","authors":"Weijie Zhang,&nbsp;He Jin,&nbsp;Shitong Lou,&nbsp;Haowei Yang,&nbsp;Xiaoyong Dai,&nbsp;Shaohua Ma","doi":"10.1002/ijc.34706","DOIUrl":"10.1002/ijc.34706","url":null,"abstract":"<p>Patient-derived organoids are gaining incremental popularity in both basic sciences and translational applications toward precision medicine and revolutionized drug discovery. However, for tumor organoids, challenges remain in low rates of organoid growth and tumor cell purity, that is, recapitulation of tumor phenotypes in constructed organoids. Here, we report a method of microfluidic droplet encapsulation that provides structural guidance for tumor cell growth and organization, where they develop into tumor organoids with high purity and high rates of modeling success, as compared to the classical organoid modeling method, that is, non-engineered organoids. The modeling efficacy and organoid quality are examined in patient-derived samples, covering esophagus, lung and colorectal cancer tissues, all proving significance in droplet-engineered organoids, as demonstrated by histological examinations.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"154 1","pages":"145-154"},"PeriodicalIF":6.4,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adding fasting-mimicking diet to first-line carboplatin-based chemotherapy is associated with better overall survival in advanced triple-negative breast cancer patients: A subanalysis of the NCT03340935 trial","authors":"Francesca Ligorio,&nbsp;Riccardo Lobefaro,&nbsp;Giovanni Fucà,&nbsp;Leonardo Provenzano,&nbsp;Lucrezia Zanenga,&nbsp;Vincenzo Nasca,&nbsp;Caterina Sposetti,&nbsp;Giulia Salvadori,&nbsp;Angela Ficchì,&nbsp;Andrea Franza,&nbsp;Antonia Martinetti,&nbsp;Elisa Sottotetti,&nbsp;Barbara Formisano,&nbsp;Catherine Depretto,&nbsp;Gianfranco Scaperrotta,&nbsp;Antonino Belfiore,&nbsp;Andrea Vingiani,&nbsp;Cristina Ferraris,&nbsp;Giancarlo Pruneri,&nbsp;Filippo de Braud,&nbsp;Claudio Vernieri","doi":"10.1002/ijc.34701","DOIUrl":"10.1002/ijc.34701","url":null,"abstract":"<p>Severe calorie restriction, in the form of cyclic fasting or fasting-mimicking diets (FMDs), boosts the antitumor activity of cytotoxic chemotherapy in mouse models of triple-negative breast cancer (TNBC). This effect is mostly mediated by fasting/FMD-induced reduction of plasma glucose concentration and by a boost in antitumor immunity. However, clinical evidence that cyclic FMD may impact on the outcomes of advanced TNBC (aTNBC) patients is lacking. We compared the overall survival (OS) of 14 aTNBC patients receiving first-line carboplatin-gemcitabine plus cyclic FMD in the context of the NCT03340935 trial with the OS of 76 consecutive aTNBC patients treated with carboplatin-based chemotherapy alone at Fondazione IRCCS Istituto Nazionale dei Tumori. Multivariable Cox regression models were used to adjust the prognostic impact of FMD for other prognostic variables. Patients undergoing cyclic FMD in combination with carboplatin-gemcitabine had better OS when compared to patients receiving chemotherapy alone (median OS 30.3 months, 95% CI 18-NR, vs 17.2 months, 95% CI 15.3-25.1, log-rank <i>P</i> value .041). Multivariable analysis confirmed an association between FMD use and better OS (HR: 0.40; 95% CI: 0.19-0.86; <i>P</i> = .019) also after propensity score-based matching according to patient ECOG PS and the presence of de novo metastatic disease (HR: 0.41; 95% CI: 0.21-0.83; <i>P</i> = .013). Cyclic FMD in combination with first-line chemotherapy may improve clinical outcomes in aTNBC patients. Our study paves the way for conducting phase II trials to investigate if cyclic FMD can increase the antitumor activity/efficacy of chemotherapy or chemoimmunotherapy in patients with early-stage TNBC or aTNBC.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"154 1","pages":"114-123"},"PeriodicalIF":6.4,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.34701","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10060987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remote modulation of WWOX by an intronic variant associated with survival of Chinese gastric cancer patients","authors":"Lei Cheng,&nbsp;Yuanyuan Chang,&nbsp;Zuguang Xia,&nbsp;Yizhen Liu,&nbsp;Xiao Liu,&nbsp;Liwen Xiong,&nbsp;Chenchen Liu,&nbsp;Xiaodong Zhu,&nbsp;Mengyun Wang,&nbsp;Lixin Qiu","doi":"10.1002/ijc.34703","DOIUrl":"10.1002/ijc.34703","url":null,"abstract":"<p>The protein WWOX was reported to be involved in cancer progression via interaction with mTOR and DNA repair pathway. We previously reported noteworthy association of some single nucleotide polymorphisms (SNPs) in mTOR and DNA repair pathways with gastric cancer (GCa) patients' survival. We hypothesized that genetic variants in <i>WWOX</i> gene could predict the survival of GCa patients. By extracting <i>WWOX</i> genetic variants from our ongoing genome-wide association study including 796 GCa patients from an Eastern Chinese population, we identified 51 out of 1913 SNPs to be significantly associated with survival of GCa patients, which passed the false positive probability tests. In particular, the intronic variant rs9922483, a G&gt;T change, was associated with 21% increased death risk for GCa patients (HR = 1.21, 95% CI = 1.04-1.42, <i>P</i> = .015). This locus was predicted to be involved in potential enhancer by bioinformatics analysis. Genotype-phenotype correlation analysis revealed decreased expression of <i>WWOX</i> by rs9922483 G&gt;T change. Mechanistically, rs9922483 locus may exhibits long-range interaction with <i>WWOX</i> promoter, and the G&gt;T change inhibited the transcriptional activity driven by <i>WWOX</i> promoter in luciferase reporter system. Especially, the G&gt;T change had an allele-specific negative effect on NR3C1 binding, and NR3C1 promoted the expression of <i>WWOX</i> in GCa cells. Further functional analysis indicated an increase in proliferation, migration and invasion of GCa cells by knockdown of <i>WWOX</i>. In conclusion, <i>WWOX</i> genetic variants may modulate survival of Chinese GCa patients by exerting remote regulatory effect on <i>WWOX</i> expression. Our results highlight the <i>cis</i>-regulatory effect of genetic variants on genes and survival modulation for GCa patients.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"154 2","pages":"307-319"},"PeriodicalIF":6.4,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10062623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age at diagnosis for lung, colon, breast and prostate cancers: An international comparative study","authors":"Hana Zahed,&nbsp;Xiaoshuang Feng,&nbsp;Mahdi Sheikh,&nbsp;Freddie Bray,&nbsp;Jacques Ferlay,&nbsp;Ophira Ginsburg,&nbsp;Meredith S. Shiels,&nbsp;Hilary A. Robbins","doi":"10.1002/ijc.34671","DOIUrl":"10.1002/ijc.34671","url":null,"abstract":"<p>Differences in the average age at cancer diagnosis are observed across countries. We therefore aimed to assess international variation in the median age at diagnosis of common cancers worldwide, after adjusting for differences in population age structure. We used IARC's Cancer Incidence in Five Continents (CI5) Volume XI database, comprising cancer diagnoses between 2008 and 2012 from population-based cancer registries in 65 countries. We calculated crude median ages at diagnosis for lung, colon, breast and prostate cancers in each country, then adjusted for population age differences using indirect standardization. We showed that median ages at diagnosis changed by up to 10 years after standardization, typically increasing in low- and middle-income countries (LMICs) and decreasing in high-income countries (HICs), given relatively younger and older populations, respectively. After standardization, the range of ages at diagnosis was 12 years for lung cancer (median age 61-Bulgaria vs 73-Bahrain), 12 years for colon cancer (60-the Islamic Republic of Iran vs 72-Peru), 10 years for female breast cancer (49-Algeria, the Islamic Republic of Iran, Republic of Korea vs 59-USA and others) and 10 years for prostate cancer (65-USA, Lithuania vs 75-Philippines). Compared to HICs, populations in LMICs were diagnosed with colon cancer at younger ages but with prostate cancer at older ages (both <i>p</i>_{LMICS-vs-HICs} &lt; 0.001). In countries with higher smoking prevalence, lung cancers were diagnosed at younger ages in both women and men (both <i>p</i>_corr &lt; 0.001). Female breast cancer tended to be diagnosed at younger ages in East Asia, the Middle East and Africa. Our findings suggest that the differences in median ages at cancer diagnosis worldwide likely reflect population-level variation in risk factors and cancer control measures, including screening.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"154 1","pages":"28-40"},"PeriodicalIF":6.4,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.34671","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10198726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}