Cancer Genomics & Proteomics最新文献

{"title":"<i>CXCL10</i> Expression in Human Colorectal Cancer Tissue and its Correlation With Serum Levels of CXCL10.","authors":"Lianbo Li, Kosuke Kanemitsu, Koji Ohnishi, Rin Yamada, Hiromu Yano, Yukio Fujiwara, Yuji Miyamoto, Yoshiki Mikami, Taizo Hibi, Hideo Baba, Yoshihiro Komohara","doi":"10.21873/cgp.20429","DOIUrl":"10.21873/cgp.20429","url":null,"abstract":"<p><strong>Background/aim: </strong>CXCL10, a member of the CXC chemokine family, plays a crucial role in immune response by facilitating the chemotaxis of CXCR3-positive immune cells. We examined the expression of CXCL10 to unravel its functional significance in colorectal cancer.</p><p><strong>Materials and methods: </strong>Bioinformatics analysis was performed to investigate CXCL10 expression and its clinicopathological relevance. Subsequently, we examined the correlation between the serum levels of CXCL10 and its expression within cancer tissues.</p><p><strong>Results: </strong>Analysis of the TCGA database revealed that elevated CXCL10 expression in CRC tissues correlates with improved long-term survival and is inversely associated with lymph node infiltration and metastasis. Insights from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes further established a connection between increased CXCL10 and co-regulated gene expression with enhanced immune activation and regulation, mediated by the inhibition of the NOD-like receptor signaling pathway. Single-cell analysis pinpointed myeloid cells and macrophages as the primary sources of CXCL10. Immunohistochemical assessments revealed that a subset of cancer cells and macrophages are positive for CXCL10 expression. CXCL10-positive cells are predominantly located at the invasive front of the tumor. Intriguingly, our findings reveal an inverse correlation between serum CXCL10 levels and its expression in cancer tissues.</p><p><strong>Conclusion: </strong>The expression of CXCL10 may play a role in mediating the inflammatory responses at the invasive front in colorectal cancer and is observed to be inversely correlated with serum CXCL10 levels. It is pivotal to elucidate the distinct roles of CXCL10 in colorectal cancer, particularly different functions of cancer-tissue CXCL10 from serum CXCL10.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 1","pages":"54-64"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10756351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048367","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":"Clinical Significance of Multi-Cancer Genome Profiling: Data from a Single Hospital in Japan.","authors":"Rika Aoyama, Hinano Nishikubo, Kyoka Kawabata, Saki Kanei, Yurie Yamamoto, Sadaaki Nishimura, Masakazu Yashiro","doi":"10.21873/cgp.20431","DOIUrl":"10.21873/cgp.20431","url":null,"abstract":"<p><strong>Background/aim: </strong>Multi-cancer genome profiling (multi-CGP) testing intends to predict the therapeutic efficacy of anticancer medication treatments for eligible patients as part of \"precision cancer care.\" The number of cases in which a new treatment was applied based on multi-CGP testing has been reported to be between 10% and 20% for all patients in Japan. This study aimed to determine the significance of multi-CGP testing in Japan by analyzing clinical data from multi-CGP testing in various solid cancers at our Hospital.</p><p><strong>Patients and methods: </strong>A total of 230 patients examined by one of three tests for multi-CGP including NCC Oncopanel, FoundationOne CDx, and FoundationOne Liquid were retrospectively enrolled. Adequate treatment for each patient was discussed at the expert panel meeting according to the results from the genome profiling tests.</p><p><strong>Results: </strong>The most frequent cancer types enrolled in this study were pancreas cancer, bowel cancer, and biliary cancer. Of the 230 cases, 106 (46%) were druggable cases, and 21 (9.1%) were administered medication. Partial response (PR) effect was found in 7 (33.3%) of the 21 cases, of which 3 were biliary cancer and 3 had a BRCA2 mutation. Of all the 21 cases, 7 (33.3%) had the maximum treatment benefit of PR. Three cases of biliary tumors were found in the 7 PR cases within the 21 cases.</p><p><strong>Conclusion: </strong>Of 230 patients, 21 were administered medication following multi-CGP testing data, especially frequent in biliary tumor patients. Multi-CGP testing might be particularly beneficial to patients with biliary tumors in Japan.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 1","pages":"79-87"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10756342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048368","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":"Metastatic Lymph Node 64 (MLN64) Expression in Gastric Cancer: The Clinical and Molecular Implications in Drug Resistance.","authors":"Amber Xinyu Li, Jimmy Jianyuan Zeng, Elyas Khan, Q Ping Dou, Xinguo Zhuang, Edison Ke Ji, Fiona Ruge, Tracey A Martin, Shuqin Jia, Wen G Jiang","doi":"10.21873/cgp.20427","DOIUrl":"10.21873/cgp.20427","url":null,"abstract":"<p><strong>Background/aim: </strong>Metastatic lymph node 64 (MLN64) is often co-amplified with ERBB2 (HER2) and plays a role in the progression of breast and prostate cancer. The present study explored the expression of MLN64 in clinical gastric cancer in association with the ERBB family and its impact on drug resistance in patients.</p><p><strong>Materials and methods: </strong>Two independent gastric cancer cohorts (n=324; n=87) were used to explore the expression profile of MLN64 in conjunction with ERBB family members in clinical gastric cancer and its association with neoadjuvant chemotherapy responses. Gastric cancer AGS and HCG27 cells with MLN64 knockdown were generated to determine the function of MLN64 in cell behavioural changes.</p><p><strong>Results: </strong>Gastric tumor tissues expressed significantly higher levels of MLN64 compared with normal tissues (p<0.01); however, MLN64 alone was a weak prognostic indicator. An integrated co-expression of MLN64, ERBB4, and NRG4 was a significant factor in assessing overall survival in both cohorts. MLN64 was a profound indicator of patient response to neoadjuvant chemotherapy. In vitro studies indicated a significant contribution of MLN64 to the response of gastric cancer cells to chemodrugs and Her-2 inhibitors. MLN64 knockdown also contributed to the adhesion and migration and suggested a possible mechanism mediated by the interaction between MLN64 and ERBBs.</p><p><strong>Conclusion: </strong>MLN64 is an indicator of patient response to neoadjuvant chemotherapy in gastric cancer. Together with the expression pattern of ERBB4, MLN64 is a poor prognostic factor for patients with gastric cancer.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 1","pages":"30-40"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10756345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048383","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":"Irradiated Cell-derived Exosomes Enhance Cell Proliferation and Radioresistance <i>via</i> the MAPK/Erk Pathway.","authors":"Yue Dong, Keisuke Tamari, Maiko Kishigami, Shohei Katsuki, Kazumasa Minami, Shotaro Tatekawa, Shinichi Shimizu, Masahiko Koizumi, Kazuhiko Ogawa","doi":"10.21873/cgp.20425","DOIUrl":"10.21873/cgp.20425","url":null,"abstract":"<p><strong>Background/aim: </strong>Radiation therapy is pivotal in cancer treatment; however, its efficacy is limited by challenges such as tumor recurrence. This study delves into the role of exosomes, which are molecular cargo-bearing vesicles, in influencing cell proliferation, radioresistance, and consequent post-irradiation tumor recurrence. Given the significance of exosomes from irradiated malignancies in diagnostics and therapy, it is vital to delineate their functional dynamics, especially in breast and cervical cancer cell lines, where the impact of irradiation on exosome behavior remains enigmatic.</p><p><strong>Materials and methods: </strong>Using MDA-MB-231 and HeLa cell lines, exosomes were isolated from the culture supernatant via ultracentrifugation. The bicinchoninic acid assay was used to measure exosome quantities in irradiated and non-irradiated cells. Radiosensitivity was assessed using colony formation assays, while the role of the MAPK/Erk signaling pathway in recipient cell proliferation and radioresistance was probed using western blotting.</p><p><strong>Results: </strong>Irradiated cells, in both MDA-MB-231 and HeLa lines, produced significantly more exosomes than their non-irradiated counterparts. Co-culturing irradiated cells with exosomes led to increased cell survival post-irradiation and enhanced cell proliferation in both cell lines. Western blotting indicated elevated p-Erk expression in such cells, underscoring the influence of the MAPK/Erk pathway in radioresistance and proliferation.</p><p><strong>Conclusion: </strong>The study establishes a potential nexus between exosome secretion and tumor resurgence following radiotherapy. The spotlight falls on the MAPK/ERK signaling conduit as a key influencer. This new knowledge provides an innovative strategy for counteracting cancer recurrence after radiotherapy, emphasizing the importance of understanding the multifaceted roles of exosomes in this context.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 1","pages":"12-17"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10756343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048382","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":"Genetic Characterization of Pediatric Mixed Phenotype Acute Leukemia (MPAL).","authors":"Ioannis Panagopoulos, Kristin Andersen, Inga Maria Rinvoll Johannsdottir, Maren Randi Tandsæther, Francesca Micci, Sverre Heim","doi":"10.21873/cgp.20424","DOIUrl":"10.21873/cgp.20424","url":null,"abstract":"<p><strong>Background/aim: </strong>Mixed phenotype acute leukemia (MPAL) is a rare hematologic malignancy in which the leukemic cells cannot be assigned to any specific lineage. The lack of well-defined, pathogenetically relevant diagnostic criteria makes the clinical handling of MPAL patients challenging. We herein report the genetic findings in bone marrow cells from two pediatric MPAL patients.</p><p><strong>Patients and methods: </strong>Bone marrow cells were examined using G-banding, array comparative genomic hybridization, RNA sequencing, reverse transcription polymerase chain reaction, Sanger sequencing, and fluorescence in situ hybridization.</p><p><strong>Results: </strong>In the first patient, the genetic analyses revealed structural aberrations of chromosomal bands 8p11, 10p11, 11q21, and 17p11, the chimeras MLLT10::PICALM and PICALM::MLLT10, and imbalances (gains/losses) on chromosomes 2, 4, 8, 13, and 21. A submicroscopic deletion in 21q was also found including the RUNX1 locus. In the second patient, there were structural aberrations of chromosome bands 1p32, 8p11, 12p13, 20p13, and 20q11, the chimeras ETV6::LEXM and NCOA6::ETV6, and imbalances on chromosomes 2, 8, 11, 12, 16, 19, X, and Y.</p><p><strong>Conclusion: </strong>The leukemic cells from both MPAL patients carried chromosome aberrations resulting in fusion genes as well as genomic imbalances resulting in gain and losses of many gene loci. The detected fusion genes probably represent the main leukemogenic events, although the gains and losses are also likely to play a role in leukemogenesis.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 1","pages":"1-11"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10756350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048371","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":"Identification of <i>TTC21A</i> as a Potential Prognostic Marker in Head and Neck Squamous Cell Carcinoma: <i>In Silico</i> Analysis.","authors":"Lili Wang, Yanping Yin, Peng Liu, Hanxiang Chen, Miao Xu","doi":"10.21873/cgp.20428","DOIUrl":"10.21873/cgp.20428","url":null,"abstract":"<p><strong>Background/aim: </strong>Tetratricopeptide repeat domain 21A (TTC21A) plays a crucial role in ciliary function and has been associated with various pathogenic processes, including carcinogenesis. However, its role in head and neck squamous cell carcinoma (HNSCC) has not been elucidated.</p><p><strong>Materials and methods: </strong>Based on the sequencing and microarray data of HNSCC from publicly available databases, the expression of TTC21A was compared between different subgroups based on clinical and molecular parameters. The survival analysis and regression analysis were conducted using the Kaplan-Meier method and the Cox method, respectively. Functional analysis was performed by the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and gene set enrichment analysis (GSEA) tools. Immune infiltration analysis was performed based on the expression of TTC21A.</p><p><strong>Results: </strong>TTC21A decreased in tumor tissues and was associated with N stage, histologic grade, HPV infection, and TP53 mutation in HNSCC. TTC21A was an independent indicator of overall survival for patients with HNSCC. A high level of TTC21A expression indicated a favorable prognosis. The TTC21A expression level was involved with immune-related signaling regulation, immune-related gene expression, and immune cell infiltration. TTC21A expression was potent in predicting immunotherapeutic benefits.</p><p><strong>Conclusion: </strong>TTC21A, as a potential predictor of favorable outcomes and immunotherapy response for HNSCC, is related to immune-related signaling regulation, immune-related gene expression, and immune cell infiltration.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 1","pages":"41-53"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10756347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048380","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":"Single-cell Transcriptomic Analysis Reveals an Immunosuppressive Network Between POSTN CAFs and ACKR1 ECs in TKI-resistant Lung Cancer.","authors":"Zhiyi Wang, Ning Yan, Hailong Sheng, Yazhi Xiao, Jingyuan Sun, Chuanhui Cao","doi":"10.21873/cgp.20430","DOIUrl":"10.21873/cgp.20430","url":null,"abstract":"<p><strong>Background/aim: </strong>Tyrosine kinase inhibitor (TKI) therapy, a principal treatment for advanced non-small cell lung cancer (NSCLC), frequently encounters the development of drug resistance. The tumor microenvironment (TME) plays a critical role in the progression of NSCLC, yet the relationship between endothelial cells (ECs) and cancer-associated fibroblasts (CAFs) subpopulations in TKI treatment resistance remains largely unexplored.</p><p><strong>Materials and methods: </strong>The BioProject database PRJNA591860 project was used to analyze scRNA-seq data including 49 advanced-stage NSCLC samples across three different time points: pre-targeted therapy (naïve), post-partial response (PR) to targeted therapy, and post-progressive disease (PD) stage. The data involved clustering stromal cells into multiple CAFs and ECs subpopulations. The abundance changes and functions of each cluster during TKI treatment were investigated by KEGG and GO analysis. Additionally, we identified specific transcription factors and metabolic pathways via DoRothEA and scMetabolism. Moreover, cell-cell communications between PD and PR stages were compared by CellChat.</p><p><strong>Results: </strong>ECs and CAFs were clustered and annotated using 49 scRNA-seq samples. We identified seven ECs subpopulations, with OIT3 ECs showing enrichment in the PR phase with a drug-resistance phenotype, and ACKR1 ECs being prevalent in the PD phase with enhanced cell adhesion. Similarly, CAFs were clustered into 7 subpopulations. PLA2G2A CAFs were predominant in PR, whereas POSTN CAFs were prevalent in PD, characterized by an immunomodulatory phenotype and increased collagen secretion. CellChat analysis showed that ACKR1 ECs strongly interacted with macrophage through the CD39 pathway and POSTN CAFs secreted Tenascin-C (TNC) to promote the progression of epithelial cells, primarily malignant ones, in PD.</p><p><strong>Conclusion: </strong>This study reveals that POSTN CAFs and ACKR1 ECs are associated with resistance to TKI treatment, based on single-cell sequencing.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 1","pages":"65-78"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10756349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048384","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":"Development and Validation of Potential Molecular Subtypes and Signatures of Thyroid Carcinoma Based on Aging-related Gene Analysis.","authors":"Zhi Li, L I Jia, Huang-Ren Zhou, L U Zhang, Meng Zhang, Juan Lv, Zhi-Yong Deng, Chao Liu","doi":"10.21873/cgp.20433","DOIUrl":"10.21873/cgp.20433","url":null,"abstract":"<p><strong>Background/aim: </strong>Thyroid carcinoma (THCA) is a cancer of the endocrine system that most commonly affects women. Aging-associated genes play a critical role in various cancers. Therefore, we aimed to gain insight into the molecular subtypes of thyroid cancer and whether senescence-related genes can predict the overall prognosis of THCA patients.</p><p><strong>Materials and methods: </strong>Thyroid carcinoma (THCA) transcriptome-related expression profiles were obtained from The Cancer Genome Atlas (TCGA) database. These profiles were randomly divided into training and validation subsets at a ratio of 1:1. Unsupervised clustering algorithms were used to compare differences between the two subtypes; prognosis-related senescence genes were used to further construct our prognostic models by univariate and multivariate Cox analyses and construct a nomogram to predict the 1-, 3-, and 5-year overall survival probability of THCA patients. In addition, we performed gene set enrichment analysis (GSEA) to predict the immune microenvironment and somatic mutations between the different risk groups. Finally, real-time PCR was used to verify the expression levels of key model genes.</p><p><strong>Results: </strong>The 'ConsensusClusterPlus' R package was used to cluster thyroid cancer into two categories (Cluster1 and Cluster2) on the basis of 46 differentially expressed aging-related genes (DE-ARGs); patients in Cluster1 demonstrated a better prognosis than those in Cluster2. Cox analysis was used to screen six prognosis-related DE-ARGs. Finally, our real-time PCR results confirmed our hypothesis.</p><p><strong>Conclusion: </strong>Differences exist between the two subtypes of thyroid cancer that help guide treatment decisions. The six DE-ARG genes have a high predictive value for risk stratifying THCA patients.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 1","pages":"102-117"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10756346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048370","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":"Impact of Mutations in Subunit Genes of the Mammalian SWI/SNF Complex on Immunological Tumor Microenvironment.","authors":"Chikako Hozumi, Akira Iizuka, Tomoatsu Ikeya, Haruo Miyata, Chie Maeda, Tadashi Ashizawa, Takeshi Nagashima, Kenichi Urakami, Yuji Shimoda, Keiichi Ohshima, Koji Muramatsu, Takashi Sugino, Akio Shiomi, Yasuhisa Ohde, Etsuro Bando, Kenichiro Furukawa, Teiichi Sugiura, Takashi Mukaigawa, Seiichiro Nishimura, Yasuyuki Hirashima, Koichi Mitsuya, Shusuke Yoshikawa, Yasuhiro Tsubosa, Hirohisa Katagiri, Masashi Niwakawa, Ken Yamaguchi, Hirotsugu Kenmotsu, Yasuto Akiyama","doi":"10.21873/cgp.20432","DOIUrl":"10.21873/cgp.20432","url":null,"abstract":"<p><strong>Background/aim: </strong>Recently, inactivating somatic mutations of SWI/SNF chromatin-remodeling genes in cancers have been reported. However, few studies have been performed regarding the immunological analysis of the tumor microenvironment (TME) in chromatin remodeling complex gene-mutated tumors. In the present study, we identified cancer patients harboring various mammalian SWI/SNF complex mutations and investigated the immunological features in those mutated cancers.</p><p><strong>Patients and methods: </strong>Cancer patients harboring any type of chromatin remodeling complex gene mutation were selected and clinicopathological features were compared between chromatin remodeling complex gene expression-low and expression-high groups. Specifically, expression levels of immune response-associated genes and cancer-associated genes were compared between the SMARCA4 expression-low and expression-high groups using volcano plot analysis.</p><p><strong>Results: </strong>Among cancers harboring PBRM1, SAMRACA4 and ARID2 gene mutations, T-cell marker and mature B-cell marker genes were up-regulated in the tumor. Specifically, T-cell effector genes (CD8B, CD40LG), central memory marker genes (CD27, CCR7) and mature B-cell marker genes (CD20, CD38, CD79 and IRF4) were up-regulated, and cancer-associated genes including MYB, MYC and AURKB genes were down-regulated in the SMARCA4 expression-low group. Remarkably, heatmap of gene expression and immunohistochemistry (IHC) data demonstrated that the tertiary lymphoid structure (TLS) gene signature of mature B cells was up-regulated in SMACA4 gene-mutated stomach cancers.</p><p><strong>Conclusion: </strong>These results suggest that immune tumor microenvironment status, such as mature B cell recruitment featuring the TLS gene signature and immune activation mediated by cancer signal down-regulation, might contribute to the classification of SMARCA4 gene-mutated tumors as immune checkpoint blockade therapy-sensitive target tumors.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 1","pages":"88-101"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10756348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048381","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":"Depletion of <i>DNTTIP2</i> Induces Cell Cycle Arrest in Pancreatic Cancer Cells.","authors":"Masato Yoshizawa, Atsushi Shiozaki, Eishi Ashihara","doi":"10.21873/cgp.20426","DOIUrl":"10.21873/cgp.20426","url":null,"abstract":"<p><strong>Background/aim: </strong>Pancreatic cancer is one of the most lethal malignant cancers worldwide and the seventh most common cause of cancer-related death in both sexes. Herein, we analyzed open access data and discovered that expression of a gene called deoxynucleotidyltransferase terminal-interacting protein 2 (DNTTIP2) is linked to prognosis of pancreatic ductal adenocarcinoma (PDAC). We then elucidated the role of DNTTIP2 in the proliferation of pancreatic cancer cells in vitro.</p><p><strong>Materials and methods: </strong>A WST-8 assay, cell cycle analysis, Annexin-V staining, quantitative reverse transcription-PCR, and western blot analysis were conducted to assess cell proliferation, cell cycle, apoptosis, and expression of DNTTIP2 mRNA and protein, respectively, in DNTTIP2-depleteted MIA-PaCa-2 and PK-1 cells.</p><p><strong>Results: </strong>Depletion of DNTTIP2 induced G₁ arrest in MIA-PaCa-2 cells by decreasing expression of special AT-rich sequence binding protein 1 (SATB1) and cyclin-dependent kinase 6 (CDK6). In addition, depletion of DNTTIP2 induced G₂ arrest in PK-1 cells by decreasing expression of CDK1. Depletion of DNTTIP2 did not induce apoptosis in MIA-PaCa-2 or PK-1 cells.</p><p><strong>Conclusion: </strong>DNTTIP2 is involved in proliferation of pancreatic cancer cells. Thus, DNTTIP2 is a potential target for inhibiting progression of pancreatic cancers.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 1","pages":"18-29"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10756344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048369","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}