Cancer Genomics & Proteomics最新文献

{"title":"Evaluation of HMGB1 Expression as a Clinical Biomarker for Cholangiocarcinoma.","authors":"Supakan Amontailak, Attapol Titapun, Apinya Jusakul, Raynoo Thanan, Phongsaran Kimawaha, Wassana Jamnongkan, Malinee Thanee, Papitchaya Sirithawat, Songpol Haohan, Anchalee Techasen","doi":"10.21873/cgp.20489","DOIUrl":"10.21873/cgp.20489","url":null,"abstract":"<p><strong>Background/aim: </strong>Cholangiocarcinoma (CCA) is an epithelial malignancy that is most prevalent in Southeast Asia, particularly in the northeast of Thailand. Identifying and establishing specific biomarkers of CCA is crucial for ensuring accurate prognosis and enabling effective treatment. High-mobility group box 1 (HMGB1) is a damage-associated molecular pattern (DAMP) molecule that can be released by dead or injured cells and is associated with tumor progression. This study aimed to investigate the expression levels of HMGB1 in CCA.</p><p><strong>Materials and methods: </strong>The clinical significance of HMGB1 levels was assessed by examining their correlation with patients' clinicopathological data. A bioinformatics analysis was conducted to examine HMGB1 mRNA expression and perform survival analysis. The expression levels of 137 tissue cases were evaluated using the immunohistochemical technique, whereas the serum levels of 31 cases were evaluated using indirect ELISA.</p><p><strong>Results: </strong>The GEPIA analysis demonstrated that HMGB1 exhibited elevated mRNA expression in CCA compared to the normal group. Immunohistochemical staining revealed that HMGB1 expression was primarily localized in the nucleus. High HMGB1 expression was observed in 57.6% of tissue samples, while low expression was detected in 42.4%. There was a significant positive correlation between high HMGB1 expression and the extrahepatic type of CCA as well as lymph node metastasis. The measurement of HMGB1 levels were assessed using indirect ELISA in 31 CCA serum samples, where 51.6% exhibited elevated concentrations of HMGB1. Elevated serum HMGB1 levels were significantly associated with advanced tumor stages and high levels of bilirubin levels.</p><p><strong>Conclusion: </strong>HMGB1 in both tissue biopsies and blood serum shows potential as a predictive biomarker in CCA patients. These biomarkers could form the basis for facilitating more effective treatment planning.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 1","pages":"81-89"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation and Function of CCL2 and N-Myc in Retinoic Acid-treated Neuroblastoma Cells.","authors":"Nanke Murra, Nina Sophie Pommert, Berit Schmidt, Reema Sami Issa, Meike Kaehler, Henrike Bruckmueller, Vera Tim, Ingolf Cascorbi, Vicki Waetzig","doi":"10.21873/cgp.20490","DOIUrl":"10.21873/cgp.20490","url":null,"abstract":"<p><strong>Background/aim: </strong>Treatment with retinoic acid (RA) often promotes neuroblastoma differentiation and growth inhibition, including the suppression of the expression of the MYCN oncogene. However, RA also targets protumoral chemokines, such as CCL2, which may contribute to the development of resistance. The present study aimed to investigate the regulation and function of CCL2 and N-Myc in RA-treated neuroblastoma cells.</p><p><strong>Materials and methods: </strong>In Kelly or SH-SY5Y cells, viability was quantified by cell fitness assays. Expression was analyzed using quantitative PCR and the regulation of proteins using enzyme-linked immunoabsorbent assays (ELISA) or western blots.</p><p><strong>Results: </strong>In MYCN-amplified Kelly cells, endogenous CCL2 levels were significantly lower compared to MYCN non-amplified SH-SY5Y cells. Treatment with 5 μM RA increased CCL2 release in both cell lines, but reduced N-Myc levels and cell numbers in Kelly cells. Over-expression of MYCN enhanced viability in SH-SY5Y cells, but did not affect RA-induced CCL2 release, while supplementation of CCL2 in Kelly cells did not prevent RA-mediated growth reduction. Impaired N-Myc or CCL2 signaling reduced the survival of all RA-treated cells and inhibition of N-Myc also decreased CCL2 levels. However, attenuated survival signaling was not generally associated with reduced levels of N-Myc or CCL2. Co-application of RA and the growth factor receptor inhibitors cediranib or crizotinib decreased N-Myc levels only in Kelly cells, while CCL2 release was dependent on the cell type and stimulus.</p><p><strong>Conclusion: </strong>CCL2 and N-Myc promote the viability of RA-treated cells, although the levels of these mediators were not consistently correlated with cellular outcomes, especially during apoptotic signaling.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 1","pages":"90-102"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RFC3 Knockdown Decreases Cervical Cancer Cell Proliferation, Migration and Invasion.","authors":"Jae Woong Koh, Seon-Joo Park","doi":"10.21873/cgp.20493","DOIUrl":"10.21873/cgp.20493","url":null,"abstract":"<p><strong>Background/aim: </strong>Replication factor C subunit 3 (RFC3) is a critical component of the replication factor C complex, which is essential for DNA replication and repair. Recent studies have highlighted the RFC3's significance in various cancer types. Herein, we aimed to elucidate its biological role in cervical cancer.</p><p><strong>Materials and methods: </strong>Cervical cancer cells were transfected with RFC3 or control siRNA. Cell viability was assessed using the MTT assay over a 4-day period and its clonogenic potential was determined using colony formation assays. Flow cytometry analysis was performed to evaluate cell cycle distribution. Transwell migration and invasion assays were performed to assess the migration and invasion abilities of cervical cancer cells.</p><p><strong>Results: </strong>RFC3 knockdown significantly inhibited cell proliferation, induced cell-cycle arrest, and decreased migration and invasion in HeLa and ME-180 cells compared to control siRNA-transfected cells.</p><p><strong>Conclusion: </strong>The crucial role of RFC3 in cervical cancer progression is highlighted. RFC3 knockdown resulted in decreased cervical cancer cell proliferation, migration and invasion, suggesting its potential as a therapeutic target in cervical cancer.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 1","pages":"127-135"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FN1 and VEGFA Are Potential Therapeutic Targets in Glioblastoma as Determined by Bioinformatics Analysis.","authors":"Mijung Im, Jungwook Roh, Wonyi Jang, Wanyeon Kim","doi":"10.21873/cgp.20488","DOIUrl":"10.21873/cgp.20488","url":null,"abstract":"<p><strong>Background/aim: </strong>Glioblastoma is the most malignant brain tumor, and despite advances in treatment, survival rates are still dismal. Therefore, a comprehensive understanding of the underlying molecular mechanisms of glioblastoma is needed. This study suggests potential therapeutic targets in glioblastoma that may provide new therapeutic insights.</p><p><strong>Materials and methods: </strong>To identify hub genes in glioblastoma, three datasets were selected from the GEO database. After screening DEGs using GEO2R, GO and KEGG analyses were performed using DAVID. The PPI network was visualized using Cytoscape and 7 hub genes were extracted. The prognostic potential of 7 hub genes was investigated using the Gliovis and GEPIA2 databases.</p><p><strong>Results: </strong>In total, 176 up-regulated and 263 down-regulated genes were identified. From the PPI network, 7 hub genes were identified including CAMK2A, DLG4, SNAP25, SYT1, MYC, FN1, and VEGFA. Out of the 7 hub genes identified, FN1 and VEGFA have been associated with a poor prognosis in glioblastoma based on the survival analysis.</p><p><strong>Conclusion: </strong>This study suggests that high levels of FN1 and VEGFA expression are associated with a poor prognosis in glioblastoma and that both genes are promising targets for glioblastoma therapy. Bioinformatics analysis of DEGs revealed putative targets that might reveal the molecular mechanisms underlying glioblastoma.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 1","pages":"70-80"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>FAM32A</i> Suppression Decreases 5-Fluorouracil-induced Apoptosis and Is Associated With Poor Prognosis in Gastric Cancer.","authors":"Yuya Agatsuma, Dai Shimizu, Shinichi Umeda, Haruyoshi Tanaka, Norifumi Hattori, Masamichi Hayashi, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Michitaka Fujiwara, Yasuhiro Kodera","doi":"10.21873/cgp.20487","DOIUrl":"10.21873/cgp.20487","url":null,"abstract":"<p><strong>Background/aim: </strong>The development of new biomarkers to predict cancer patient prognosis is expected to aid in treatment selection, contributing to improved outcomes. In this study, we extracted a candidate gene associated with patient prognosis from a public database and investigated the molecular and biological functions and clinical significance of the gene in gastric cancer.</p><p><strong>Materials and methods: </strong>We analyzed The Cancer Genome Atlas database and identified the family with sequence similarity 32 member a (FAM32A) as a candidate gene. We investigated the clinicopathological significance of FAM32A mRNA and protein expression in 300 and 176 gastric cancer patients respectively. We evaluated the molecular and biological functions by suppressing FAM32A expression in gastric cancer cell lines using small interfering RNA.</p><p><strong>Results: </strong>In the polymerase chain reaction (PCR) cohort, low FAM32A expression group showed significantly shorter disease-specific survival (DSS) [hazard ratio (HR)=1.586; 95% confidence interval (95% CI)=1.056-2.382, p=0.026]. In the immunohistochemistry cohort, the FAM32A(-) group had significantly shorter overall survival (HR=1.703; 95% CI=1.050-2.764, p=0.031) and DSS (HR=2.123; 95% CI=1.185-3.804, p=0.011). Multivariate Cox hazard analysis revealed that FAM32A(-) was an independent adverse prognostic factor for DSS (p<0.001). AGS cell lines with FAM32A knockdown exhibited significant resistance to 5-fluorouracil (5-FU) and reduced apoptosis upon 5-FU administration. Gene set enrichment analysis indicated decreased gene expression related to the p53 signaling pathway in AGS cells with FAM32A knockdown that were treated with 5-FU.</p><p><strong>Conclusion: </strong>FAM32A suppression decreases 5-FU-induced apoptosis. Low FAM32A expression is associated with a poor prognosis in gastric cancer, suggesting its potential as a biomarker.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 1","pages":"55-69"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two Different <i>NF1</i> Pathogenic Variants in a Family With Neurofibromatosis Type 1.","authors":"Tabea I Hartung, Lan Kluwe, Reinhard E Friedrich, Said C Farschtschi","doi":"10.21873/cgp.20485","DOIUrl":"10.21873/cgp.20485","url":null,"abstract":"<p><strong>Background/aim: </strong>Neurofibromatosis type 1 (NF1) is a genetic disorder with an incidence of approximately one in 3,000. More than half of the patients have new de novo pathogenic variants of the NF1 gene. In most family cases, all family members share an identical NF1-variant. The aim of the study was to investigate the very rare phenomenon of de novo variants in cases of familial neurofibromatosis type 1 and highlight its implications for genetic testing and counseling.</p><p><strong>Patients and methods: </strong>Patients underwent clinical examination in our NF outpatient clinic and genetic testing for the NF1-gene was performed by targeted sequencing. All family members were profiled by short-tandem repeat marker analysis. Additionally, a probability calculation was performed for this extremely rare event.</p><p><strong>Results: </strong>In one NF1 family consisting of mother, father, and two sons, two different pathogenic variants of the NF1 gene were found. The father and one son share one NF1-variant and the other son carries a different de novo NF1-variant. Neither of these two NF1-variants was found in the unaffected mother. Short-tandem repeat analysis confirmed the paternity and revealed that the two sons inherited two different NF1-alleles from their father. The probability of two different NF1-variants occurring in one family is calculated as 1:9,000,000.</p><p><strong>Conclusion: </strong>Two different NF1-variants in one family is an extremely rare phenomenon: yet its occurrence is not impossible and therefore should be considered in genetic diagnosis and counselling. For an offspring with the indication for neurofibromatosis type 1, but lacking the familial pathogenic variant, a screening of the whole NF1-gene is necessary to detect potential new pathogenic variants and for exact diagnosis.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 1","pages":"41-45"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunohistochemical Analysis of a1-Acid Glycoprotein and Tumor Associated Macrophages in Clear Cell Renal Cell Carcinoma.","authors":"Ayano Ezaki, Hiromu Yano, Cheng Pan, Yukio Fujiwara, Toshiki Anami, Yuki Ibe, Youjiro Ozaki, Hidekazu Nishizawa, Takanobu Motoshima, Junji Yatsuda, Hiroshi Watanabe, Toru Maruyama, Toru Takeo, Tomomi Kamba, Yoshihiro Komohara","doi":"10.21873/cgp.20491","DOIUrl":"10.21873/cgp.20491","url":null,"abstract":"<p><strong>Background/aim: </strong>α1-Acid glycoprotein (AGP), also known as orosomucoid, is an acute-phase protein that has been found increased in plasma of cancer patients. This study investigates the role of AGP expression in clear cell renal cell carcinoma (ccRCC) and its association with clinical outcomes.</p><p><strong>Materials and methods: </strong>We investigated the correlation between AGP levels and the prognosis of ccRCC through an analysis of The Cancer Genome Atlas (TCGA) database. To examine AGP expression and its clinicopathological associations, immunostaining was performed on paraffin-embedded tissue samples of 92 ccRCC cases.</p><p><strong>Results: </strong>AGP expression was found to be higher in RCC cell lines compared to normal renal epithelial cells. Analysis of the TCGA dataset showed that patients with AGP gene expression had significantly worse overall survival. However, AGP expression was not correlated with age, sex, or cancer stage. A mouse monoclonal antibody against AGP was generated. This antibody reacted with human and mouse hepatocytes, but not in AGP-deficient mice. From 92 examined ccRCC cases, AGP protein expression was detected in 89 cases, with only 3 being negative. AGP expression levels did not correlate with clinicopathological factors, such as age, tumor size, or nuclear grade. CD14, a receptor of AGP, was found to be expressed in Iba1-positive monocytes and tumor-associated macrophages (TAMs) but not in other cell types like lymphocytes or cancer cells. No significant correlation was found between AGP expression and the number of Iba1-positive cells in ccRCC tissues. Iba1-positive cells were correlated with Fuhrman grade, and patients with ≥30% Iba1-positive cells were, on average, significantly younger and had more aggressive tumor.</p><p><strong>Conclusion: </strong>AGP expression is linked to poorer survival in ccRCC, but its association with immune cell infiltration (via Iba1-positive cells) is unclear.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 1","pages":"103-111"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complex Genetic Evolution and Treatment Challenges in Myeloid Neoplasms: A Case of Persistent t(2;3)(p15~23;q26)/<i>MECOM</i> Rearrangement, <i>SF3B1</i> Mutation, and Transient <i>TNIP1::PDGFRB</i> Chimera.","authors":"Kristin Andersen, Geir E Tjønnfjord, Malu Lian Hestdalen, Signe Spetalen, Ioannis Panagopoulos","doi":"10.21873/cgp.20483","DOIUrl":"10.21873/cgp.20483","url":null,"abstract":"<p><strong>Background/aim: </strong>Myelodysplastic syndromes (MDSs) are clonal bone marrow disorders characterized by ineffective hematopoiesis. They are classified based on morphology and genetic alterations, with SF3B1 variants linked to favorable prognosis and MECOM rearrangements associated with poor outcomes. The combined effects of these alterations remain unclear. We report an MDS patient carrying both SF3B1 and MECOM alterations who developed transient eosinophilia accompanied by a TNIP1::PDGFRB chimera in a subset of MECOM-affected cells.</p><p><strong>Case report: </strong>A 73-year-old woman was diagnosed with myeloid neoplasia with excess blasts and multilineage dysplasia (MDS-EB1). Six months later, SF3B1 mutations were identified, leading to a diagnosis of MDS-SF3B1. Despite azacitidine treatment, her condition worsened, showing hypercellular bone marrow and eosinophilia. Genetic analysis revealed a t(2;3)(p15~23;q26)/MECOM rearrangement and TNIP1::PDGFRB chimera. Imatinib eradicated eosinophilia and reduced TNIP1::PDGFRB-positive cells, but the MECOM-clone persisted. Subsequent treatments, including hydroxyurea, mercaptopurine, and low-dose cytarabine, were ineffective. FLT3 mutations and high EVI1 transcript levels were later detected. The patient succumbed to progressive disease.</p><p><strong>Conclusion: </strong>This case highlights the complexity of MDS and the importance of genetic abnormalities in treatment planning. Persistent MECOM rearrangement and the TNIP1::PDGFRB chimera emphasize the need for further research into resistance mechanisms.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 1","pages":"24-33"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of Cyclin Dependent Kinase Inhibitor 1A Genotypes to Childhood Acute Lymphocytic Leukemia Risk in Taiwan.","authors":"Chao-Chun Chen, Chung-Lin Tsai, Jen-Sheng Pei, Huey-En Tzeng, Pei-Chen Hsu, DA-Chuan Cheng, Jiunn-Cherng Lin, Chia-Wen Tsai, DA-Tian Bau, Wen-Shin Chang","doi":"10.21873/cgp.20486","DOIUrl":"10.21873/cgp.20486","url":null,"abstract":"<p><strong>Background/aim: </strong>The disruption of cell-cycle control can lead to an imbalance in cell proliferation, often accompanied by genomic instability, which in turn can facilitate carcinogenesis. This study aimed to examine the impact of CDKN1A rs1801270 and rs1059234 polymorphisms on the risk of childhood acute lymphocytic leukemia (ALL) in Taiwan.</p><p><strong>Materials and methods: </strong>The genotypes of CDKN1A rs1801270 and rs1059234 in 266 childhood ALL cases and 266 controls were determined using PCR-RFLP techniques.</p><p><strong>Results: </strong>The genotypic and allelic frequencies for CDKN1A rs1801270 and rs1059234 did not significantly differ between childhood ALL cases and controls (all p>0.05). However, stratified analysis revealed that the CDKN1A rs1801270 AA variant was associated with a reduced risk of childhood ALL in males (OR=0.40, 95%CI=0.20-0.82, p=0.0178). Additionally, the AC and AA genotypes of rs1801270 were linked to a lower risk classification for childhood ALL and longer survival times (OR=0.57 and 0.31, 95%CI=0.33-0.97 and 0.18-0.56, p=0.0538 and 0.0001, respectively). No significant associations were found for rs1059234 in the stratified analyses (p>0.05 for all).</p><p><strong>Conclusion: </strong>Although CDKN rs1801270 and rs1059234 genotypes were not associated with an overall risk of childhood ALL, CDKN1A rs1801270 polymorphism may serve as a protective predictor in males and as a potential marker for better prognosis of childhood ALL. Validation in larger and more diverse populations is necessary to confirm the feasibility of this predictor.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 1","pages":"46-54"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>KRAS</i> Mutations in Cholangiocarcinoma: Prevalence, Prognostic Value, and <i>KRAS</i> G12/G13 Detection in Cell-Free DNA.","authors":"Pitchasak Thongyoo, Jarin Chindaprasirt, Chaiwat Aphivatanasiri, Piyapharom Intarawichian, Waritta Kunprom, Sarinya Kongpetch, Anchalee Techasen, Watcharin Loilome, Nisana Namwat, Attapol Titapun, Apinya Jusakul","doi":"10.21873/cgp.20492","DOIUrl":"10.21873/cgp.20492","url":null,"abstract":"<p><strong>Background/aim: </strong>Cholangiocarcinoma (CCA) is an aggressive hepatobiliary malignancy characterized by genomic heterogeneity. KRAS mutations play a significant role in influencing patient prognosis and guiding therapeutic decision-making. This study aimed to determine the prevalence and prognostic significance of KRAS mutations in CCA, asses the detection of KRAS G12/G13 mutations in plasma cell-free DNA (cfDNA), and evaluate the prognostic value of KRAS G12/G13 mutant allele frequency (MAF) in cfDNA in relation to clinicopathological data and patient survival.</p><p><strong>Materials and methods: </strong>A retrospective analysis of 937 CCA patients was performed using data from cBioPortal to examine KRAS mutation profiles and their association with survival. Plasma from 101 CCA patients was analyzed for KRAS G12/G13 mutations in the cfDNA using droplet digital PCR, and the results were compared with tissue-based sequencing from 78 matched samples.</p><p><strong>Results: </strong>KRAS driver mutations were found in 15.6% of patients, with common variants being G12D (37.0%), G12V (24.0%) and Q61H (8.2%). Patients harboring KRAS mutations exhibited decreased overall and recurrence-free survival. KRAS G12/G13 mutations were detected in 14.9% of cfDNA samples, showing moderate concordance with tissue sequencing, and achieving 80% sensitivity and 93% specificity. Elevated KRAS G12/G13 MAF in cfDNA, combined with high CA19-9 levels, correlated with poorer survival outcomes.</p><p><strong>Conclusion: </strong>The presence of KRAS mutations was associated with poor survival in CCA, underscoring the importance of KRAS mutations as prognostic markers. The detection of KRAS mutations in cfDNA demonstrated potential as a promising non-invasive alternative for mutation detection and, when combined with CA19-9 levels, may improve prognostic efficacy in CCA.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 1","pages":"112-126"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}