Cancer Genomics & Proteomics最新文献

{"title":"Association of Androgen Receptor and PD-L1 Expression in Upper Urinary Tract Urothelial Carcinoma.","authors":"Yohei Okuda, Taigo Kato, Kazutoshi Fujita, Hiroaki Fushimi, Hiroshi Miyamoto, George J Netto, Norio Nonomura","doi":"10.21873/cgp.20435","DOIUrl":"10.21873/cgp.20435","url":null,"abstract":"<p><strong>Background/aim: </strong>The response to immune checkpoint inhibitors (ICIs) or enfortumab vedotin is limited in patients with upper urinary tract urothelial carcinoma (UTUC), and the development of new targeted therapy for UTUC is eagerly needed. Several biomarkers, including programmed cell death-ligand 1 (PD-L1), have already been reported as predictors of response to ICIs therapy for UTUC. Recently, several studies have shown that steroid hormone receptors, including the androgen receptor (AR), are associated with progression of urothelial carcinoma.</p><p><strong>Materials and methods: </strong>We prepared tissue microarrays (TMA) from paraffin blocks of UTUC specimens in 99 non-metastatic UTUC patients who underwent radical nephroureterectomy. With these TMA sections, we performed immunohistochemical staining for PD-L1 and AR and examined PD-L1 and AR expression levels in tumor cells. In addition, we analyzed the correlation between these markers and clinical prognosis in UTUC cases.</p><p><strong>Results: </strong>PD-L1 was positive in 24 (24%) of the 99 samples, whereas AR was positive in 20 (20%) patients. AR-negative samples had significantly higher PD-L1 expression level than that the AR-positive samples (mean value 4.70% versus 2.55%, p=0.0324). Among AR-positive cases, patients with absence of PD-L1 expression had significantly lower cancer-specific survival (CSS) than that in PD-L1 expression-positive cases (p=0.049), although PD-L1 expression had no significant impact on CSS in AR-negative cases (p=0.920).</p><p><strong>Conclusion: </strong>Our findings suggest that AR is the promising target for UTUC treatment, especially in PD-L1-negative cases.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 2","pages":"137-143"},"PeriodicalIF":2.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10905274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995696","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":"POLD1 Is Required for Cell Cycle Progression by Overcoming DNA Damage in Malignant Pleural Mesothelioma.","authors":"Daiki Shimizu, Miku Ishibashi, Tadaaki Yamada, Yuki Toda, Shigekuni Hosogi, Eishi Ashihara","doi":"10.21873/cgp.20437","DOIUrl":"10.21873/cgp.20437","url":null,"abstract":"<p><strong>Background/aim: </strong>The prognosis of patients with malignant pleural mesothelioma (MPM) remains poor due to lack of effective therapeutic targets. DNA damage caused by long-time exposure to asbestos fibers has been associated with the development of MPM, with mutations at genes encoding DNA damage repair (DDR)-related molecules frequently expressed in patients with MPM. The present study was designed to identify novel therapeutic targets in MPM using large public databases, such as The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression project (GTEx) focused on DDR pathways.</p><p><strong>Materials and methods: </strong>The correlations between mRNA expression levels of DDR-related genes and overall survival (OS) were analyzed in mesothelioma patients in TCGA mesothelioma (TCGA-MESO) datasets. The anti-tumor effects of small interfering RNAs (siRNA) against DDR-related genes associated with OS were subsequently tested in MPM cell lines.</p><p><strong>Results: </strong>High levels of mRNA encoding DNA polymerase delta 1, catalytic subunit (POLD1) were significantly associated with reduced OS in patients with MPM (p<0.001, Log-rank test). In addition, siRNA targeting POLD1 (siPOLD1) caused cell cycle arrest at the G₁/S checkpoint and induced apoptosis involving accumulation of DNA damage in MPM cell lines.</p><p><strong>Conclusion: </strong>POLD1 plays essential roles in overcoming DNA damage and cell cycle progression at the G₁/S checkpoint in MPM cells. These findings suggest that POLD1 may be a novel therapeutic target in MPM.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 2","pages":"158-165"},"PeriodicalIF":2.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10905272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995701","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":"Thioredoxin Reductase Inhibitor Suppresses the Local Progression of Rhabdomyosarcoma With PDX Models.","authors":"Hideyuki Kinoshita, Seiko Kinoshita, Hiroto Kamoda, Yoko Hagiwara, Seiji Ohtori, Tsukasa Yonemoto","doi":"10.21873/cgp.20439","DOIUrl":"10.21873/cgp.20439","url":null,"abstract":"<p><strong>Background/aim: </strong>Chemoresistance in rhabdomyosarcoma (RMS) is associated with poor survival, necessitating the development of novel anticancer drugs. Auranofin (AUR), an anti-rheumatic drug, is a thioredoxin reductase (TXNRD) inhibitor with anticancer properties. Although patient-derived xenograft (PDX) models are essential for studying cancer biology, reports on sarcomas using the PDX model are scarce because of their rarity. This study aimed to investigate the effectiveness of AUR treatment in RMS using a PDX model to evaluate its impact on local progression.</p><p><strong>Materials and methods: </strong>A 20-year-old woman who was diagnosed with alveolar RMS was used to generate the PDX model. RMS PDX tumors were implanted in nude mice and divided into non-treated (vehicle) and treated (AUR) groups. Tumor volume and weight were evaluated, and immunohistochemical staining was performed to evaluate local progression of the sarcoma. The relationship between the TXNRD-1 expression and survival probability of patients with RMS was evaluated using publicly available expression cohorts.</p><p><strong>Results: </strong>AUR significantly suppressed RMS tumor progression over time. It also significantly suppressed the tumor size and weight at the time of excision. Histological evaluation showed that AUR induced oxidative stress in the PDX mouse models and inhibited the local progression of RMS by inducing apoptosis. High TXNRD-1 expression was found to be a negative prognostic factor for overall survival in patients with RMS.</p><p><strong>Conclusion: </strong>AUR-induced inhibition of TXNRDs can significantly impede the local progression of RMS through the oxidative stress-apoptosis pathway as demonstrated in PDX models. Thus, targeting TXNRD inhibition may be a promising therapeutic strategy for the treatment of RMS.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 2","pages":"178-185"},"PeriodicalIF":2.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10905273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995725","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>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}