Carcinogenesis最新文献

{"title":"Retraction of: Genetic and clinical characteristics of BRCA-associated hereditary breast cancer in the West region of Kazakhstan.","authors":"","doi":"10.1093/carcin/bgad083","DOIUrl":"10.1093/carcin/bgad083","url":null,"abstract":"","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"181"},"PeriodicalIF":4.7,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138797658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of biomarkers for the early detection of non-small cell lung cancer: a systematic review and meta-analysis.","authors":"Eithar Mohamed, Daniel J García Martínez, Mohammad-Salar Hosseini, Si Qi Yoong, Daniel Fletcher, Simon Hart, Barbara-Ann Guinn","doi":"10.1093/carcin/bgad091","DOIUrl":"10.1093/carcin/bgad091","url":null,"abstract":"<p><p>Lung cancer (LC) causes few symptoms in the earliest stages, leading to one of the highest mortality rates among cancers. Low-dose computerised tomography (LDCT) is used to screen high-risk individuals, reducing the mortality rate by 20%. However, LDCT results in a high number of false positives and is associated with unnecessary follow-up and cost. Biomarkers with high sensitivities and specificities could assist in the early detection of LC, especially in patients with high-risk features. Carcinoembryonic antigen (CEA), cytokeratin 19 fragments and cancer antigen 125 have been found to be highly expressed during the later stages of LC but have low sensitivity in the earliest stages. We determined the best biomarkers for the early diagnosis of LC, using a systematic review of eight databases. We identified 98 articles that focussed on the identification and assessment of diagnostic biomarkers and achieved a pooled area under curve of 0.85 (95% CI 0.82-0.088), indicating that the diagnostic performance of these biomarkers when combined was excellent. Of the studies, 30 focussed on single/antigen panels, 22 on autoantibodies, 31 on miRNA and RNA panels, and 15 suggested the use of circulating DNA combined with CEA or neuron-specific enolase (NSE) for early LC detection. Verification of blood biomarkers with high sensitivities (Ciz1, exoGCC2, ITGA2B), high specificities (CYFR21-1, antiHE4, OPNV) or both (HSP90α, CEA) along with miR-15b and miR-27b/miR-21 from sputum may improve early LC detection. Further assessment is needed using appropriate sample sizes, control groups that include patients with non-malignant conditions, and standardised cut-off levels for each biomarker.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"1-22"},"PeriodicalIF":4.7,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138797643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long non-coding RNA NRAV in the 12q24.31 risk locus drives gastric cancer development through glucose metabolism reprogramming.","authors":"Yan Zhang, Yun Gao, Fengyuan Li, Qi Qi, Qian Li, Yuanliang Gu, Zhonghua Zheng, Beiping Hu, Tianpei Wang, Erbao Zhang, Hao Xu, Li Liu, Tian Tian, Guangfu Jin, Caiwang Yan","doi":"10.1093/carcin/bgad080","DOIUrl":"10.1093/carcin/bgad080","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) serve as vital candidates to mediate cancer risk. Here, we aimed to identify the risk single-nucleotide polymorphisms (SNPs)-induced lncRNAs and to investigate their roles in gastric cancer (GC) development. Through integrating the differential expression analysis of lncRNAs in GC tissues and expression quantitative trait loci analysis in normal stomach tissues and GC tissues, as well as genetic association analysis based on GC genome-wide association studies and an independent validation study, we identified four lncRNA-related SNPs consistently associated with GC risk, including SNHG7 [odds ratio (OR) = 1.16, 95% confidence interval (CI): 1.09-1.23], NRAV (OR = 1.11, 95% CI: 1.05-1.17), LINC01082 (OR = 1.16, 95% CI: 1.08-1.22) and FENDRR (OR = 1.16, 95% CI: 1.07-1.25). We further found that a functional SNP rs6489786 at 12q24.31 increases binding of MEOX1 or MEOX2 at a distal enhancer and results in up-regulation of NRAV. The functional assays revealed that NRAV accelerates GC cell proliferation while inhibits GC cell apoptosis. Mechanistically, NRAV decreases the expression of key subunit genes through the electron transport chain, thereby driving the glucose metabolism reprogramming from aerobic respiration to glycolysis. These findings suggest that regulating lncRNA expression is a crucial mechanism for risk-associated variants in promoting GC development.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"23-34"},"PeriodicalIF":4.7,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72208458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALDH2 dysfunction and alcohol cooperate in cancer stem cell enrichment.","authors":"Samuel Flashner, Masataka Shimonosono, Yasuto Tomita, Norihiro Matsuura, Shinya Ohashi, Manabu Muto, Andres J Klein-Szanto, J Alan Diehl, Che-Hong Chen, Daria Mochly-Rosen, Kenneth I Weinberg, Hiroshi Nakagawa","doi":"10.1093/carcin/bgad085","DOIUrl":"10.1093/carcin/bgad085","url":null,"abstract":"<p><p>The alcohol metabolite acetaldehyde is a potent human carcinogen linked to esophageal squamous cell carcinoma (ESCC) initiation and development. Aldehyde dehydrogenase 2 (ALDH2) is the primary enzyme that detoxifies acetaldehyde in the mitochondria. Acetaldehyde accumulation causes genotoxic stress in cells expressing the dysfunctional ALDH2E487K dominant negative mutant protein linked to ALDH2*2, the single nucleotide polymorphism highly prevalent among East Asians. Heterozygous ALDH2*2 increases the risk for the development of ESCC and other alcohol-related cancers. Despite its prevalence and link to malignant transformation, how ALDH2 dysfunction influences ESCC pathobiology is incompletely understood. Herein, we characterize how ESCC and preneoplastic cells respond to alcohol exposure using cell lines, three-dimensional organoids and xenograft models. We find that alcohol exposure and ALDH2*2 cooperate to increase putative ESCC cancer stem cells with high CD44 expression (CD44H cells) linked to tumor initiation, repopulation and therapy resistance. Concurrently, ALHD2*2 augmented alcohol-induced reactive oxygen species and DNA damage to promote apoptosis in the non-CD44H cell population. Pharmacological activation of ALDH2 by Alda-1 inhibits this phenotype, suggesting that acetaldehyde is the primary driver of these changes. Additionally, we find that Aldh2 dysfunction affects the response to cisplatin, a chemotherapeutic commonly used for the treatment of ESCC. Aldh2 dysfunction facilitated enrichment of CD44H cells following cisplatin-induced oxidative stress and cell death in murine organoids, highlighting a potential mechanism driving cisplatin resistance. Together, these data provide evidence that ALDH2 dysfunction accelerates ESCC pathogenesis through enrichment of CD44H cells in response to genotoxic stressors such as environmental carcinogens and chemotherapeutic agents.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"95-106"},"PeriodicalIF":3.3,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10859731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-1304 targets KLK11 to regulate gastric cancer cell proliferation through the mTOR signaling pathway.","authors":"Yi Ding, Zehua Wang, Chen Chen, Dongyu Li, Wenjia Wang, Yongxu Jia, Yanru Qin","doi":"10.1093/carcin/bgad077","DOIUrl":"10.1093/carcin/bgad077","url":null,"abstract":"<p><strong>Objective: </strong>Gastric cancer (GC) is prevalent worldwide but has a dismal prognosis, and its molecular and pathogenic pathways remain unknown. Kallikrein 11 (KLK11) has a reduced expression in GC and may be a promising biomarker.</p><p><strong>Method: </strong>Herein, the function of KLK11 in GC and its regulatory mechanism was studied. Gene sequencing and quantitative reverse transcription-polymerase chain reaction were used to determine the expression of KLK11 in GC and precancerous lesions. Cell function tests and flow cytometry were conducted to determine the proliferative capacity and cell cycle of GC cells, respectively. A luciferase reporter test confirmed the interaction between RNA molecules. The mTOR/4E-BP1 signaling pathway was analyzed using western blotting.</p><p><strong>Result: </strong>KLK11 has a suppressed expression in GC samples. KLK11 decreased the proliferative capacity of GC cells, by inhibiting the degree of mTOR/4E-BP1 phosphorylation. In contrast, miR-1304 increased GC cell proliferation by inhibiting KLK11. Moreover, KLK11 was able to limit in vivo GC cell proliferation.</p><p><strong>Conclusion: </strong>These findings reveal a promising strategy to prevent and treat GC by targeting the KLK11-mediated mTOR/4E-BP1 cascade.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"45-56"},"PeriodicalIF":4.7,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SLCO1B3 and SLCO2B1 genotypes, androgen deprivation therapy, and prostate cancer outcomes: a prospective cohort study and meta-analysis.","authors":"Sai Harisha Rajanala, Anna Plym, Jane B Vaselkiv, Ericka M Ebot, Konstantina Matsoukas, Zhike Lin, Goutam Chakraborty, Sarah C Markt, Kathryn L Penney, Gwo-Shu M Lee, Lorelei A Mucci, Philip W Kantoff, Konrad H Stopsack","doi":"10.1093/carcin/bgad075","DOIUrl":"10.1093/carcin/bgad075","url":null,"abstract":"<p><p>Solute carrier organic anion (SLCO) transporters (OATP transporters) are involved in cellular uptake of drugs and hormones. Germline variants in SLCO1B3 and SLCO2B1 have been implicated in prostate cancer progression and therapy response, including to androgen deprivation and statin medications, but results have appeared heterogeneous. We conducted a cohort study of five single-nucleotide polymorphisms (SNPs) in SLCO1B3 and SLCO2B1 with prior evidence among 3208 men with prostate cancer who participated in the Health Professionals Follow-up Study or the Physicians' Health Study, following participants prospectively after diagnosis over 32 years (median, 14 years) for development of metastases and cancer-specific death (lethal disease, 382 events). Results were suggestive of, but not conclusive for, associations between some SNPs and lethal disease and differences by androgen deprivation and statin use. All candidate SNPs were associated with SLCO mRNA expression in tumor-adjacent prostate tissue. We also conducted a systematic review and harmonized estimates for a dose-response meta-analysis of all available data, including 9 further studies, for a total of 5598 patients and 1473 clinical events. The A allele of the exonic SNP rs12422149 (14% prevalence), which leads to lower cellular testosterone precursor uptake via SLCO2B1, was associated with lower rates of prostate cancer progression (hazard ratio per A allele, 0.80; 95% confidence interval, 0.69-0.93), with little heterogeneity between studies (I2, 0.27). Collectively, the totality of evidence suggests a strong association between inherited genetic variation in SLCO2B1 and prostate cancer prognosis, with potential clinical use in risk stratification related to androgen deprivation therapy.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"35-44"},"PeriodicalIF":3.3,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10859730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49674597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD48 suppresses proliferation and migration as an immune-related prognostic signature in the cervical cancer immune microenvironment.","authors":"Yue Ma, Zhuo Yang, Jing Liu, Danbo Wang","doi":"10.1093/carcin/bgad039","DOIUrl":"10.1093/carcin/bgad039","url":null,"abstract":"<p><p>Cervical cancer (CC) is one of the most common malignant tumors in gynecology. Immunotherapy and targeted therapy are two particularly effective treatments. In this study, weighted gene co-expression network analysis and CIBERSORT algorithm that quantifies the composition of immune cells were used to analyze CC expression data based on the GEO database and identify modules related to T cells. Five candidate hub genes were identified by tumor-infiltrating immune cells estimation and Kaplan-Meier survival analysis according to CC data from The Cancer Genome Atlas (TCGA). Chemotherapeutic response, methylation, and gene mutation analyses were implemented so that the five candidate hub genes identified may be the potential biomarkers and therapeutic targets which were related to T cell infiltration. Moreover, the results of RT-qPCR revealed that CD48 was a tumor suppressor gene, which was negatively correlated with CC stages, lymph node metastasis, and differentiation. Furthermore, the functional study verified that the interference of CD48 was able to boost the proliferation and migration ability in vitro and the growth of transplanted tumors in vivo. Overall, we identified molecular targets related to immune infiltration and prognosis, regarded CD48 as a key molecule involved in the progression of CC, thus providing new insights into the development of molecular therapy and immunotherapeutics against CC.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"57-68"},"PeriodicalIF":4.7,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9585950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircCDK17 promotes the proliferation and metastasis of ovarian cancer cells by sponging miR-22-3p to regulate CD147 expression.","authors":"Bin Qu, Lisha Sun, Ping Xiao, Haoming Shen, Yuxi Ren, Jing Zhang","doi":"10.1093/carcin/bgad079","DOIUrl":"10.1093/carcin/bgad079","url":null,"abstract":"<p><p>Ovarian cancer (OC) is a common malignancy in women of reproductive age. Circular RNAs (circRNAs) are emerging players in OC progression. We investigated the function and mechanism of circular RNA hsa_circ_0027803 (circCDK17) in OC pathogenesis. Real‑time PCR (RT-qPCR) and western blot were utilized for gene and protein expression analysis, respectively. Cell counting kit‑8 (CCK-8), EdU and Transwell assays investigated OC cell proliferation, migration and invasion. The associations between circCDK17, miR-22-3p and CD147 were examined by dual-luciferase reporter and RNA-protein immunoprecipitation (RIP) assays. The in vivo model of OC nude mice was constructed to explore the role of circCDK17. CircCDK17 was increased in OC tissue and cells, and patients with higher expression of circCDK17 had a shorter survival. CircCDK17 downregulation inhibited OC cell proliferation, migration and invasion, and reduced epithelial-mesenchymal transition (EMT)-related markers. In vivo experiments showed that circCDK17 silencing inhibited OC tumor growth and metastasis. CircCDK17 depletion reduced CD147 level via sponging miR-22-3p. MiR-22-3p knockdown overturned effect of circCDK17 depletion on OC cell proliferation, migration and invasion. Meanwhile, overexpressed CD147 restored functions of circCDK17 downregulation on OC development. CircCDK17 is an important molecule that regulates OC pathogenic process through miR-22-3p/CD147.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"83-94"},"PeriodicalIF":4.7,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89716952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA CCAT1 participates in pancreatic ductal adenocarcinoma progression by forming a positive feedback loop with c-Myc.","authors":"Chundong Cheng, Zonglin Liu, Danxi Liu, Hua Chen, Yongwei Wang, Bei Sun","doi":"10.1093/carcin/bgad076","DOIUrl":"10.1093/carcin/bgad076","url":null,"abstract":"<p><p>Long noncoding RNAs (lncRNAs) play fundamental roles in cancer development; however, the underlying mechanisms for a large proportion of lncRNAs in pancreatic ductal adenocarcinoma (PDAC) have not been elucidated. The expression of colon cancer-associated transcript-1 (CCAT1) in PDAC specimens and cell lines was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The function of CCAT1 was examined in vitro and in vivo. The interactions among CCAT1, miR-24-3p and c-Myc were determined by bioinformatics analysis, RNA immunoprecipitation (RIP), dual-luciferase reporter assay, and rescue experiments. CCAT1 was significantly increased in PDAC, positively correlated with PDAC progression and predicted a worse prognosis. Furthermore, CCAT1 enhanced Adenosine triphosphate (ATP) production to facilitate PDAC cell proliferation, colony formation and motility in vitro and tumor growth in vivo. CCAT1 may serve as an miR-24-3p sponge, thereby counteracting its repression by c-Myc expression. Reciprocally, c-Myc may act as a transcription factor to alter CCAT1 expression by directly targeting its promoter region, thus forming a positive feedback loop with CCAT1. Collectively, these results demonstrate that a positive feedback loop of CCAT1/miR-24-3p/c-Myc is involved in PDAC development, which may serve as a biomarker and therapeutic target for PDAC.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"69-82"},"PeriodicalIF":4.7,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71478314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S. Perwez Hussain, 1960-2023.","authors":"Stefan Ambs","doi":"10.1093/carcin/bgad092","DOIUrl":"https://doi.org/10.1093/carcin/bgad092","url":null,"abstract":"","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139080496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}