Cancer Genomics & Proteomics最新文献

{"title":"OPLAH Protein Expression Stratifies the Prognosis of Patients With Squamous Cell Carcinoma of the Esophagus.","authors":"Dai Shimizu,&nbsp;Mitsuro Kanda,&nbsp;Takayoshi Kishida,&nbsp;Shunsuke Nakamura,&nbsp;Masahiro Sasahara,&nbsp;Sei Ueda,&nbsp;Yusuke Sato,&nbsp;Yoshikuni Inokawa,&nbsp;Norifumi Hattori,&nbsp;Masamichi Hayashi,&nbsp;Chie Tanaka,&nbsp;Satoru Motoyama,&nbsp;Yasuhiro Kodera","doi":"10.21873/cgp.20386","DOIUrl":"https://doi.org/10.21873/cgp.20386","url":null,"abstract":"<p><strong>Background/aim: </strong>Squamous cell carcinoma is one of the major subtypes of esophageal carcinoma, and the 5-year overall survival rate of esophageal squamous cell carcinoma patients who underwent curative treatment remains below 40%. We aimed to detect and validate the prognosticators of esophageal squamous cell carcinoma in patients who underwent radical esophagectomy.</p><p><strong>Materials and methods: </strong>Comprehensive analysis of transcriptome and clinical data from The Cancer Genome Atlas revealed OPLAH as one of the differentially expressed genes between esophageal squamous cell carcinoma tissues and normal esophageal mucosa. OPLAH expression changes were significantly associated with a patient prognosis. OPLAH protein levels were further evaluated by immunohisto-chemistry in esophageal squamous cell carcinoma tissues (n=177) as well as in serum samples (n=54) using ELISA.</p><p><strong>Results: </strong>OPLAH mRNA was significantly overexpressed in esophageal squamous cell carcinoma tissues compared to normal esophageal mucosa, and patients with high OPLAH mRNA expression have a significantly poorer prognosis, according to The Cancer Genome Atlas data. The high staining intensity of OPLAH protein in esophageal squamous cell carcinoma tissue clearly stratified patient prognosis. According to multivariable analysis, high OPLAH protein expression was an independent prognostic factor for survival after surgery. Pre-neoadjuvant chemotherapy serum OPLAH protein concentrations were significantly associated with clinical tumor depth and node positivity and, consequently, with advanced clinical stage. The serum OPLAH protein concentration was significantly decreased by neoadjuvant chemotherapy.</p><p><strong>Conclusion: </strong>OPLAH protein expression in cancerous tissue and serum may have clinical utility towards stratifying prognosis of patients with esophageal squamous cell carcinoma.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320559/pdf/cgp-20-343.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9758152","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":"Localization of <i>EGFR</i> Mutations in Non-small-cell Lung Cancer Tissues Using Mutation-specific PNA-DNA Probes.","authors":"Hajime Shigeto,&nbsp;Haruo Miyata,&nbsp;Tadashi Ashizawa,&nbsp;Akira Iizuka,&nbsp;Yasufumi Kikuchi,&nbsp;Chikako Hozumi,&nbsp;Chie Maeda,&nbsp;Ken Yamaguchi,&nbsp;Shohei Yamamura,&nbsp;Yasuto Akiyama","doi":"10.21873/cgp.20389","DOIUrl":"10.21873/cgp.20389","url":null,"abstract":"<p><strong>Background/aim: </strong>Epidermal growth factor receptor (EGFR) signaling inhibitors are potent therapeutic agents for EGFR-mutant non-small-cell lung cancer, but the effects of such inhibitors on the localization of EGFR mutations in tumor tissues remain to be elucidated. Thus, a simple and efficient technology for the detection of mutations in tumor tissue specimens needs to be developed.</p><p><strong>Materials and methods: </strong>Using an EGFR mutation-specific peptide nucleic acid (PNA)-DNA probe, the EGFR mutation-positive part of whole NSCLC tissues was visualized by immunofluorescence. Formalin-fixed paraffin-embedded sections obtained from A549, NCI-H1975, HCC827 and PC-9 tumors transplanted into nude mice were subjected to staining using PNA-DNA probes specific for the mRNA sequences producing the L858R, del E746-A750 and T790M mutations.</p><p><strong>Results: </strong>The probes for the L858R mutation showed intense positive staining in H1975 cells, and the probe for the del E746-A750 mutation exhibited positive staining specifically in HCC827 and PC-9 tumors. On the other hand, A549 tumors without EGFR mutation did not show any significant staining for any PNA-DNA probe. In combination staining, the addition of cytokeratin stain increased the positive staining rate of each PNA-DNA probe. In addition, the positive staining rate of the probes for the L858R mutation was comparable to that of the antibody to EGFR L858R mutated protein.</p><p><strong>Conclusion: </strong>PNA-DNA probes specific for EGFR mutations might be useful tools to detect heterogeneous mutant EGFR expression in cancer tissues and efficiently evaluate the effect of EGFR signaling inhibitors on tissues of EGFR-mutant cancer.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320556/pdf/cgp-20-375.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9758155","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":"Involvement of AKT/PI3K Pathway in Sanguinarine's Induced Apoptosis and Cell Cycle Arrest in Triple-negative Breast Cancer Cells.","authors":"Samia S Messeha, Sophie Noel, Najla O Zarmouh, Tracy Womble, Lekan M Latinwo, Karam F A Soliman","doi":"10.21873/cgp.20385","DOIUrl":"10.21873/cgp.20385","url":null,"abstract":"Abstract Background/Aim: Chemotherapy resistance in triple-negative breast cancer (TNBC) cells is well documented. Therefore, it is necessary to develop safer and more effective therapeutic agents to enhance the outcomes of chemotherapeutic agents. The natural alkaloid sanguinarine (SANG) has demonstrated therapeutic synergy when coupled with chemotherapeutic agents. SANG can also induce cell cycle arrest and trigger apoptosis in various cancer cells. Materials and Methods: In this study, we investigated the molecular mechanism underlying SANG activity in MDA-MB-231 and MDA-MB-468 cells as two genetically different models of TNBC. We employed various assays including Alamar Blue to measure the effect of SANG on cell viability and proliferation rate, Flow cytometry analysis to study the potential of the compound to induce apoptosis and cell cycle arrest, quantitative qRT PCR apoptosis array to measure the expression of different genes mediating apoptosis, and the western system was used to analyze the impact of the compound on AKT protein expression. Results: SANG lowered cell viability and disrupted cell cycle progression in both cell lines. Furthermore, S-phase cell cycle arrest-mediated apoptosis was found to be the primary contributor to cell growth inhibition in MDA-MB-231 cells. SANG-treated TNBC cells showed significantly up-regulated mRNA expression of 18 genes associated with apoptosis, including eight TNF receptor superfamily (TNFRSF), three members of the BCL2 family, and two members of the caspase (CASP) family in MDA-MB-468 cells. In MDA-MB-231 cells, two members of the TNF superfamily and four members of the BCL2 family were affected. The western study data showed the inhibition of AKT protein expression in both cell lines concurrent with up-regulated BCL2L11 gene. Our results point to the AKT/PI3K signaling pathway as one of the key mechanisms behind SANG-induced cell cycle arrest and death. Conclusion: SANG shows anticancer properties and apoptosis-related gene expression changes in the two TNBC cell lines and suggests AKT/PI3K pathway implication in apoptosis induction and cell cycle arrest. Thus, we propose SANG’s potential as a solitary or supplementary treatment agent against TNBC.","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320563/pdf/cgp-20-323.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9767018","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":"Targeting Autophagy With the Synergistic Combination of Chloroquine and Rapamycin as a Novel Effective Treatment for Well-differentiated Liposarcoma.","authors":"Noriyuki Masaki,&nbsp;Yusuke Aoki,&nbsp;Koya Obara,&nbsp;Yutaro Kubota,&nbsp;Michael Bouvet,&nbsp;Jun Miyazaki,&nbsp;Robert M Hoffman","doi":"10.21873/cgp.20384","DOIUrl":"https://doi.org/10.21873/cgp.20384","url":null,"abstract":"<p><strong>Background/aim: </strong>Liposarcoma is a type of soft-tissue sarcoma arising from fat tissue. It is relatively common among soft-tissue sarcomas. Chloroquine (CQ), an antimalarial drug, can inhibit autophagy and induce apoptosis in cancer cells. Rapamycin (RAPA) is an inhibitor of mTOR. The combination of RAPA and CQ is a strong inhibitor of autophagy. Previously, we showed that the combination of RAPA and CQ was effective against a de-differentiated liposarcoma patient-derived orthotopic xenograft (PDOX) mouse model. In the present study, we investigated the mechanism of efficacy of the combination of RAPA and CQ to target autophagy in a well-differentiated liposarcoma (WDLS) cell line in vitro.</p><p><strong>Materials and methods: </strong>The human WDLS cell line 93T449 was used. The WST-8 assay was used to test the cytotoxicity of RAPA and CQ. Western blotting was used to detect microtubule-associated protein light chain 3-II (LC3-II) which is a component of autophagosomes. Immunostaining of LC3-II was also performed for autophagosome analysis. Τhe TUNEL assay was used to detect apoptotic cells, and apoptosis-positive cells were counted in three randomly selected microscopic fields for statistical validation.</p><p><strong>Results: </strong>RAPA alone and CQ alone inhibited the viability of 93T449 cells. The combination of RAPA and CQ inhibited 93T449 cell viability significantly more than either drug alone and increased the number of autophagosomes which led to extensive apoptosis.</p><p><strong>Conclusion: </strong>The combination of RAPA and CQ increased the number of autophagosomes which led to apoptosis in 93T449 WDLS cells, suggesting novel effective treatment for this recalcitrant cancer by targeting autophagy.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320558/pdf/cgp-20-317.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9748961","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":"Next Generation Sequencing Analysis and its Benefit for Targeted Therapy of Lung Adenocarcinoma.","authors":"Vlastimil Kulda,&nbsp;Jiri Polivka,&nbsp;Martin Svaton,&nbsp;Tomas Vanecek,&nbsp;Marcela Buresova,&nbsp;Katerina Houfkova,&nbsp;Mahyar Sharif Bagheri,&nbsp;Tereza Knizkova,&nbsp;Bohuslava Vankova,&nbsp;Jindra Windrichova,&nbsp;Petr Macan,&nbsp;Vaclav Babuska,&nbsp;Martin Pesta","doi":"10.21873/cgp.20392","DOIUrl":"https://doi.org/10.21873/cgp.20392","url":null,"abstract":"<p><strong>Background/aim: </strong>Targeted therapy has become increasingly important in treating lung adenocarcinoma, the most common subtype of lung cancer. Next-generation sequencing (NGS) enables precise identification of specific genetic alterations in individual tumor tissues, thereby guiding targeted therapy selection. This study aimed to analyze mutations present in adenocarcinoma tissues using NGS, assess the benefit of targeted therapy and evaluate the progress in availability of targeted therapies over last five years.</p><p><strong>Patients and methods: </strong>The study included 237 lung adenocarcinoma patients treated between 2018-2020. The Archer FusionPlex CTL panel was used for NGS analysis.</p><p><strong>Results: </strong>Gene variants covered by the panel were detected in 57% patients and fusion genes in 5.9% patients. At the time of the study, 34 patients (14.3% of patients) were identified with a targetable variant. Twenty-five patients with EGFR variants, 8 patients with EML4-ALK fusion and one patient with CD74-ROS1 fusion received targeted therapy. Prognosis of patients at advanced stages with EGFR variants treated by tyrosine kinase inhibitors and patients with EML4-ALK fusion treated by alectinib was significantly favorable compared to patients without any targetable variant treated by chemotherapy (p=0.0172, p=0.0096, respectively). Based on treatment guidelines applicable in May 2023, the number of patients who could profit from targeted therapy would be 64 (27.0% of patients), this is an increase by 88% in comparison to recommendations valid in 2018-2020.</p><p><strong>Conclusion: </strong>As lung adenocarcinoma patients significantly benefit from targeted therapy, the assessment of mutational profiles using NGS could become a crucial approach in the routine management of oncological patients.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320561/pdf/cgp-20-404.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9748962","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":"Targeted Therapy for BRAF V600E Positive Pancreatic Adenocarcinoma: Two Case Reports.","authors":"Shivani Shah, Tabeer Rana, Pragnan Kancharla, Dulabh Monga","doi":"10.21873/cgp.20391","DOIUrl":"10.21873/cgp.20391","url":null,"abstract":"<p><strong>Background/aim: </strong>Pancreatic ductal adenocarcinoma (PDAC) is a malignancy that typically portends a poor prognosis, with a median overall survival ranging from eight to twelve months in patients with metastatic disease. Novel modalities of therapy, primarily targeted therapy, are now considered for patients with targetable mutations, such as BRAF mutations based on next generation sequencing. BRAF mutations specifically within pancreatic adenocarcinoma remain rare with an incidence of approximately 3%. Previous research on BRAF mutated pancreatic adenocarcinoma is extremely scarce, limited primarily to case reports; therefore, little is known regarding this entity.</p><p><strong>Case report: </strong>We seek to contribute to prior literature with the presentation of two cases of patients with BRAF V600E + pancreatic adenocarcinoma, who did not have a favorable response to initial systemic chemotherapy and were both subsequently treated with targeted therapy (dabrafenib and trametinib). Each of the patients has sustained a favorable response and there is no evidence of progression thus far on dabrafenib and trametinib, highlighting the potential benefit of targeted therapy in these patients.</p><p><strong>Conclusion: </strong>These cases emphasize the importance of early next generation sequencing and the consideration of BRAF targeted treatment in this patient population, especially if a response to initial chemotherapy is not sustained.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320564/pdf/cgp-20-398.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9748964","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":"Bioinformatics Analysis of Novel Targets for Treating Cervical Cancer by Immunotherapy Based on Immune Escape.","authors":"Ying-Hao Han,&nbsp;DA-Yu Ma,&nbsp;Seung-Jae Lee,&nbsp;Ying-Ying Mao,&nbsp;Shuai-Yang Sun,&nbsp;Mei-Hua Jin,&nbsp;Hu-Nan Sun,&nbsp;Taeho Kwon","doi":"10.21873/cgp.20390","DOIUrl":"https://doi.org/10.21873/cgp.20390","url":null,"abstract":"<p><strong>Background/aim: </strong>Cervical cancer (CC) is a high-risk disease in women, and advanced CC can be difficult to treat even with surgery, radiotherapy, and chemotherapy. Hence, developing more effective treatment methods is imperative. Cancer cells undergo a renewal process to escape immune surveillance and then attack the immune system. However, the underlying mechanisms remain unclear. Currently, only one immunotherapy drug has been approved by the Food and Drug Administration for CC, thus indicating the need for and importance of identifying key targets related to immunotherapy.</p><p><strong>Materials and methods: </strong>Data on CC and normal cervical tissue samples were downloaded from the National Center for Biotechnology Information database. Transcriptome Analysis Console software was used to analyze differentially expressed genes (DEGs) in two sample groups. These DEGs were uploaded to the DAVID online analysis platform to analyze biological processes for which they were enriched. Finally, Cytoscape was used to map protein interaction and hub gene analyses.</p><p><strong>Results: </strong>A total of 165 up-regulated and 362 down-regulated genes were identified. Among them, 13 hub genes were analyzed in a protein-protein interaction network using the Cytoscape software. The genes were screened out based on the betweenness centrality value and average degree of all nodes. The hub genes were as follows: ANXA1, APOE, AR, C1QC, CALML5, CD47, CTSZ, HSP90AA1, HSP90B1, NOD2, THY1, TLR4, and VIM. We identified the following 12 microRNAs (miRNAs) that target the hub genes: hsa-miR-2110, hsa-miR-92a-2-5p, hsa-miR-520d-5p, hsa-miR-4514, hsa-miR-4692, hsa-miR-499b-5p, hsa-miR-5011-5p, hsa-miR-6847-5p, hsa-miR-8054, hsa-miR-642a-5p, hsa-miR-940, and hsa-miR-6893-5p.</p><p><strong>Conclusion: </strong>Using bioinformatics, we identified potential miRNAs that regulated the cancer-related genes and long noncoding RNAs (lncRNAs) that regulated these miRNAs. We further elucidated the mutual regulation of mRNAs, miRNAs, and lncRNAs involved in CC occurrence and development. These findings may have major applications in the treatment of CC by immunotherapy and the development of drugs against CC.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320560/pdf/cgp-20-383.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9748968","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":"Combination of Urinary MiR-501 and MiR-335 With Current Clinical Diagnostic Parameters as Potential Predictive Factors of Prostate Biopsy Outcome.","authors":"Jaroslav Juracek,&nbsp;Marie Madrzyk,&nbsp;Karolina Trachtova,&nbsp;Michaela Ruckova,&nbsp;Julia Bohosova,&nbsp;Dominik A Barth,&nbsp;Martin Pichler,&nbsp;Michal Stanik,&nbsp;Ondrej Slaby","doi":"10.21873/cgp.20383","DOIUrl":"https://doi.org/10.21873/cgp.20383","url":null,"abstract":"<p><strong>Background: </strong>The detection of prostate cancer (PCa) is currently based on prostate-specific antigen (PSA) quantification as an initial screening followed by ultrasound-guided transrectal biopsy. However, the high rate of false-negative biopsies often leads to inappropriate treatment. Therefore, new molecular biomarkers, such as urine microRNAs (miRNAs), are a possible way to redefine PCa diagnostics.</p><p><strong>Patients and methods: </strong>Urine samples of 356 patients undergoing prostate biopsy (256 cases with confirmed prostate cancer, 100 cases with negative prostate biopsy) at the Masaryk Memorial Cancer Institute (Czech Republic) and additional 36 control subjects (healthy controls, benign prostatic hyperplasia - BPH) were divided into the discovery and validation cohorts and analyzed. In the discovery phase, small RNA sequencing was performed using the QIAseq miRNA Library Kit and the NextSeq 500 platform. Identified miRNA candidates were validated by the RT-qPCR method in the independent validation phase.</p><p><strong>Results: </strong>Using the small RNA sequencing method, we identified 12 urine miRNAs significantly dysregulated between PCa patients and controls. Furthermore, independent validation showed the ability of miR-501-3p and the quantitative miR-335:miR-501 ratio to distinguish between PCa patients and patients with negative prostate biopsy. The subsequent combination of the miR-335:miR-501 ratio with PSA and total prostate volume (TPV) using logistic regression exceeded the analytical accuracy of standalone parameters [area under curve (AUC)=0.75, positive predictive value (PPV)=0.85, negative predictive value (NPV)=0.51)] and discriminated patients according to biopsy outcome.</p><p><strong>Conclusion: </strong>Combination of miR-335:miR-501 ratio with PSA and total prostate volume was able to identify patients with negative prostate biopsy and could potentially streamline decision making for biopsy indication.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148065/pdf/cgp-20-308.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9404715","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":"The Role of Apoptotic Genes and Protein-Protein Interactions in Triple-negative Breast Cancer.","authors":"Getinet M Adinew, Samia Messeha, Equar Taka, Shade A Ahmed, Karam F A Soliman","doi":"10.21873/cgp.20379","DOIUrl":"10.21873/cgp.20379","url":null,"abstract":"<p><strong>Background/aim: </strong>Compared to other breast cancer types, triple-negative breast cancer (TNBC) has historically had few treatment alternatives. Therefore, exploring and pinpointing potentially implicated genes could be used for treating and managing TNBC. By doing this, we will provide essential data to comprehend how the genes are involved in the apoptotic pathways of the cancer cells to identify potential therapeutic targets. Analysis of a single genetic alteration may not reveal the pathogenicity driving TNBC due to the high genomic complexity and heterogeneity of TNBC. Therefore, searching through a large variety of gene interactions enabled the identification of molecular therapeutic genes.</p><p><strong>Materials and methods: </strong>This study used integrated bioinformatics methods such as UALCAN, TNM plotter, PANTHER, GO-KEEG and PPIs to assess the gene expression, protein-protein interaction (PPI), and transcription factor interaction of apoptosis-regulated genes.</p><p><strong>Results: </strong>Compared to normal breast tissue, gene expressions of BNIP3, TNFRSF10B, MCL1, and CASP4 were downregulated in UALCAN. At the same time, BIK, AKT1, BAD, FADD, DIABLO, and CASP9 was down-regulated in bc-GeneExMiner v4.5 mRNA expression (BCGM) databases. Based on GO term enrichment analysis, the cellular process (GO:0009987), which has about 21 apoptosis-regulated genes, is the top category in the biological processes (BP), followed by biological regulation (GO:0065007). We identified 29 differentially regulated pathways, including the p53 pathway, angiogenesis, apoptosis signaling pathway, and the Alzheimer's disease presenilin pathway. We examined the PPIs between the genes that regulate apoptosis; CASP3 and CASP9 interact with FADD, MCL1, TNF, TNFRSRF10A, and TNFRSF10; additionally, CASP3 significantly forms PPIs with CASP9, DFFA, and TP53, and CASP9 with DIABLO. In the top 10 transcription factors, the androgen receptor (AR) interacts with five apoptosis-regulated genes (p<0.0001; q<0.01), followed by retinoic acid receptor alpha (RARA) (p<0.0001; q<0.01) and ring finger protein (RNF2) (p<0.0001; q<0.01). Overall, the gene expression profile, PPIs, and the apoptosis-TF interaction findings suggest that the 27 apoptosis-regulated genes might be used as promising targets in treating and managing TNBC. Furthermore, from a total of 27 key genes, CASP2, CASP3, DAPK1, TNF, TRAF2, and TRAF3 were significantly correlated with poor overall survival in TNBC (p-value <0.05); they could play important roles in the progression of TNBC and provide attractive therapeutic targets that may offer new candidate molecules for targeted therapy.</p><p><strong>Conclusion: </strong>Our findings demonstrate that CASP2, CASP3, DAPK1, TNF, TRAF2, and TRAF3 were substantially associated with the overall survival rate (OS) difference of TNBC patients out of a total of 27 specific genes used in this study, which may play crucial roles in the development of ","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148064/pdf/cgp-20-247.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9404710","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":"Breast Cancer: Circular RNAs Mediating Efficacy in Preclinical <i>In Vivo</i> Models.","authors":"Ulrich H Weidle,&nbsp;Hung-En Hsia,&nbsp;Ulrich Brinkmann","doi":"10.21873/cgp.20377","DOIUrl":"https://doi.org/10.21873/cgp.20377","url":null,"abstract":"<p><p>In order to identify new targets and treatment modalities for breast cancer, we searched the literature for circular RNAs (circRNAs) with efficacy in preclinical breast cancer-related in vivo models. From our search, we identified 26 up-regulated and six down-regulated circRNAs which mediate efficacy in breast cancer-related preclinical in vivo models. We discuss reconstitution and inhibition of the identified circRNAs, as well as druggability and validation of the targets identified in the context of chemoresistance, inhibition of proliferation and metastasis. Pathways driven by suppressors of cytokines and high-mobility group proteins, nuclear factor B and Hippo signaling emerged as important drivers of tumor growth and metastasis. The role of trefoil factor-1 with respect to metastasis of estrogen receptor-positive breast cancer also merits further investigation. In addition, mucin 19 has emerged as an unexplored target for treatment of breast cancer.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148070/pdf/cgp-20-222.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9404713","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}