Zhilin Sha, Qingxiang Gao, Lei Wang, Ni An, Yingjun Wu, Dong Wei, Tong Wang, Chen Liu, Yang Shen
{"title":"Investigating the Cell Origin and Liver Metastasis Factors of Colorectal Cancer by Single-Cell Transcriptome Analysis","authors":"Zhilin Sha, Qingxiang Gao, Lei Wang, Ni An, Yingjun Wu, Dong Wei, Tong Wang, Chen Liu, Yang Shen","doi":"10.2147/ott.s454295","DOIUrl":"https://doi.org/10.2147/ott.s454295","url":null,"abstract":"<strong>Background:</strong> Colorectal cancer (CRC) is one of the deadliest causes of death by cancer worldwide. Liver metastasis (LM) is the main cause of death in patients with CRC. Therefore, identification of patients with the greatest risk of liver metastasis is critical for early treatment and reduces the mortality of patients with colorectal cancer liver metastases.<br/><strong>Methods:</strong> Initially, we characterized cell composition through single-cell transcriptome analysis. Subsequently, we employed copy number variation (CNV) and pseudotime analysis to delineate the cellular origins of LM and identify LM-related epithelial cells (LMECs). The LM-index was constructed using machine learning algorithms to forecast the relative abundance of LMECs, reflecting the risk of LM. Furthermore, we analyzed drug sensitivity and drug targeted gene expression in LMECs and patients with a high risk of LM. Finally, functional experiments were conducted to determine the biological roles of metastasis-related gene in vitro.<br/><strong>Results:</strong> Single-cell RNA sequencing analysis revealed different immune landscapes between primary CRC and LM tumor. LM originated from chromosomal variants with copy number loss of chr1 and chr6p and copy number gain of chr7 and chr20q. We identified the LMECs cluster and found LM-associated pathways such as Wnt/beta-catenin signaling and KRAS signaling. Subsequently, we identified ten metastasis-associated genes, including SOX4, and established the LM-index, which correlates with poorer prognosis, higher stage, and advanced age. Furthermore, we screened two drugs as potential candidates for treating LM, including Linsitinib_1510, Lapatinib_1558. Immunohistochemistry results demonstrated significantly elevated SOX4 expression in tumor samples compared to normal samples. Finally, in vitro experiments verified that silencing SOX4 significantly inhibited tumor cell migration and invasion.<br/><strong>Conclusion:</strong> This study reveals the possible cellular origin and driving factors of LM in CRC at the single cell level, and provides a reference for early detection of CRC patients with a high risk of LM.<br/><br/>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140617218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fang Ren, Christina Shrestha, Huirong Shi, Fangfang Sun, Minghui Zhang, Yuan Cao, Gailing Li
{"title":"Targeting of KDM5A by miR-421 in Human Ovarian Cancer Suppresses the Progression of Ovarian Cancer Cells [Retraction]","authors":"Fang Ren, Christina Shrestha, Huirong Shi, Fangfang Sun, Minghui Zhang, Yuan Cao, Gailing Li","doi":"10.2147/ott.s474059","DOIUrl":"https://doi.org/10.2147/ott.s474059","url":null,"abstract":"Retraction for the article Targeting of KDM5A by miR-421 in Human Ovarian Cancer Suppresses the Progression of Ovarian Cancer Cells","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140617450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Suqing Liu, Fengling Li, Qinghua Cao, Ning Li, Qian Gao
{"title":"A Case Study of Gastric Adenocarcinoma and Squamous Cell Carcinoma of the Cervix","authors":"Suqing Liu, Fengling Li, Qinghua Cao, Ning Li, Qian Gao","doi":"10.2147/ott.s435811","DOIUrl":"https://doi.org/10.2147/ott.s435811","url":null,"abstract":"<strong>Abstract:</strong> Gastric adenocarcinoma (GAS) is a rare subtype of mucinous adenocarcinoma characterized by gastric differentiation and is unrelated to human papillomavirus (HPV) infection. This report discusses a 40-year-old female who presented with abdominal distension accompanied by increased abdominal circumference. CT of the abdomen and pelvis showed a large 21.0&ast12.7&ast26.0 cm mass later diagnosed as GAS combined with squamous cell carcinoma on surgical pathology. Immunohistological staining of GAS was positive for CK7, MUC6, PAX-8 CEA, and P53 (wild type) and negative for CDX2, CK20, ER, PR, P16, and WT1. The proliferative index (Ki-67) was 20%. Immunohistochemical staining of squamous cell carcinoma was positive for P16 and P53 (wild type), and the proliferative index (Ki-67) was 90%. However, the pathogenesis and molecular mechanisms of GAS have not been fully elucidated. As more cases are identified and reported, additional targeted therapies can be developed and tested in these patients.<br/><br/><strong>Keywords:</strong> cervical cancer, gastric type, adenocarcinoma<br/>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140566110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Primary Epithelioid Angiosarcoma of the Jejunal Mesentery Causing Abdominal Bleeding: Case Report and Literature Review","authors":"Peiyuan Yang, Qiong Wu, Yang Zhou, Yongchao Li","doi":"10.2147/ott.s453698","DOIUrl":"https://doi.org/10.2147/ott.s453698","url":null,"abstract":"<strong>Abstract:</strong> Gastrointestinal angiosarcoma is an extremely rare malignant tumor of the digestive tract, characterized by a very poor prognosis, with few patients surviving more than 1 year after diagnosis. This case report describes a 71-year-old female patient with a 3-year history of intermittent abdominal pain and significant exacerbation of abdominal pain and bloating 2 weeks prior to treatment. After surgical treatment, the pathological and immunohistochemical diagnosis was primary epithelioid angiosarcoma of the jejunal mesentery. The patient refused postoperative adjuvant chemotherapy and died 4 months after diagnosis due to widespread systemic metastasis. In addition, this article reviews 38 previously reported cases of primary gastrointestinal angiosarcoma, aiming to further understand angiosarcoma and thus guide clinical practitioners in providing more comprehensive treatment approaches.<br/><br/><strong>Keywords:</strong> gastrointestinal, angiosarcoma, hematochezia<br/>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140566218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ziwei Wang, Mengyao Li, Ling Bi, Xueqing Hu, Yan Wang
{"title":"Traditional Chinese Medicine in Regulating Tumor Microenvironment","authors":"Ziwei Wang, Mengyao Li, Ling Bi, Xueqing Hu, Yan Wang","doi":"10.2147/ott.s444214","DOIUrl":"https://doi.org/10.2147/ott.s444214","url":null,"abstract":"<strong>Abstract:</strong> Tumor microenvironment (TME) is a complex and integrated system containing a variety of tumor-infiltrating immune cells and stromal cells. They are closely connected with cancer cells and influence the development and progression of cancer. Traditional Chinese medicine (TCM) is an important complementary therapy for cancer treatment in China. It mainly eliminates cancer cells by regulating TME. The aim of this review is to systematically summarize the crosstalk between tumor cells and TME, and to summarize the research progress of TCM in regulating TME. The review is of great significance in revealing the therapeutic mechanism of action of TCM, and provides an opportunity for the combined application of TCM and immunotherapy in cancer treatment.<br/><br/><strong>Keywords:</strong> cancer, tumor microenvironment, traditional Chinese medicine, anti-tumor effects<br/>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140566108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MAP2K1 K57N Conferred an Acquired Resistance to Furmonertinib, Dabrafenib and Trametinib Combined Therapy in Advanced Lung Adenocarcinoma with EGFR Mutation and BRAF V600E","authors":"Xiang Tan, Zuotao Wu, Mingwu Chen","doi":"10.2147/ott.s454902","DOIUrl":"https://doi.org/10.2147/ott.s454902","url":null,"abstract":"<strong>Abstract:</strong> Previous case reports have demonstrated the effectiveness of combination therapy involving EGFR TKI, <em>BRAF</em> inhibitor dabrafenib, and <em>MEK</em> inhibitor trametinib in metastatic non-small-cell lung cancer (NSCLC) patients with acquired <em>BRAF</em> V600E and <em>EGFR</em> mutations. However, the current literature does not provide any reports on the presence of resistant mutations in response to the administration of three-drug combination therapy. Exploring the resistance mechanism of targeted therapy is helpful to optimize the subsequent treatment strategy of patients. Herein, we report a case of a patient with advanced <em>EGFR</em> positive lung adenocarcinoma harboring an acquired <em>BRAF</em> V600E mutation who responded to the combination of furmonertinib, dabrafenib, and trametinib therapy. Unexpectedly, a <em>MAP2K1</em> K57N acquired mutation was identified by NGS (Next-generation sequencing) analysis of re-biopsy tumor tissue after the patient was resistant to three-drug therapy. As far as we know, this is the first report demonstrating that the efficacy of using combination of furmonertinib and <em>BRAF</em>/<em>MEK</em> inhibitors and the <em>MAP2K1</em> K57N mutation serves as a resistant mechanism to the three-drug therapy. This novel finding not only revealed a new resistant mutation but also had important implications for the identification of effective patients to EGFR/BRAF/MEK combination therapy.<br/><br/><strong>Keywords:</strong> MAP2K1, furmonertinib, lung adenocarcinoma, EGFR, mutation<br/>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140566217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"miR-31 Modulates Liver Cancer HepG2 Cell Apoptosis and Invasion via ROCK1/F-Actin Pathways [Retraction]","authors":"Xin Zhang, Lan Xu, Ting Yang","doi":"10.2147/ott.s472230","DOIUrl":"https://doi.org/10.2147/ott.s472230","url":null,"abstract":"Retraction for the article miR-31 Modulates Liver Cancer HepG2 Cell Apoptosis and Invasion via ROCK1/F-Actin Pathways","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140566206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MicroRNA-155-3p Promotes Breast Cancer Progression Through Down-Regulating CADM1 [Retraction]","authors":"Guochao Zhang, Lele Zhong, Hao Luo, Shibing Wang","doi":"10.2147/ott.s472068","DOIUrl":"https://doi.org/10.2147/ott.s472068","url":null,"abstract":"Retraction for the article MicroRNA-155-3p promotes breast cancer progression through down-regulating CADM1","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140566203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of miR-330-3p on Invasion, Migration and EMT of Gastric Cancer Cells by Targeting PRRX1-Mediated Wnt/β-Catenin Signaling Pathway [Retraction]","authors":"Bingqiang Ma, Jianxun Ma, Yili Yang, Xueyuan He, Xinmin Pan, Zhan Wang, Yaowen Qian","doi":"10.2147/ott.s472066","DOIUrl":"https://doi.org/10.2147/ott.s472066","url":null,"abstract":"Retraction for the article Effects of miR-330-3p on Invasion, Migration and EMT of Gastric Cancer Cells by Targeting PRRX1-Mediated Wnt/β-Catenin Signaling Pathway","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140566210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Huang, Sun Wu, Yuan Zhang, Lihua Wang, Yan Guo
{"title":"Antitumor Effect of Triptolide in T-Cell Lymphoblastic Lymphoma by Inhibiting Cell Viability, Invasion, and Epithelial–Mesenchymal Transition via Regulating the PI3K/AKT/mTOR Pathway [Retraction]","authors":"Yan Huang, Sun Wu, Yuan Zhang, Lihua Wang, Yan Guo","doi":"10.2147/ott.s472070","DOIUrl":"https://doi.org/10.2147/ott.s472070","url":null,"abstract":"Retraction for the article Antitumor effect of triptolide in T-cell lymphoblastic lymphoma by inhibiting cell viability, invasion, and epithelial–mesenchymal transition via regulating the PI3K/AKT/mTOR pathway","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140566209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}