Experimental Hematology and Oncology, Год журнала: 2023, Номер 12(1)
Опубликована: Ноя. 27, 2023
Язык: Английский
Journal of Medical Virology, Год журнала: 2023, Номер 95(6)
Опубликована: Июнь 1, 2023
Abstract Cervical squamous cell carcinoma (SCC) and adenocarcinoma (AD) are the main histological types of human papillomavirus‐related cervical cancer. However, there few reports on type‐specific molecular differences between SCC AD. Here, we used unbiased droplet‐based single‐cell RNA sequencing to elucidate cellular AD in tumor heterogeneity, microenvironment (TME). A total 61 723 cells from three patients, were collected divided into nine types. Epithelial exhibited high intra‐ interpatient heterogeneity functional diversity. Signaling pathways, such as epithelial‐to‐mesenchymal‐transition (EMT), hypoxia inflammatory response upregulated SCC, while cycle‐related signaling pathways highly enriched was associated with infiltration cytotoxicity CD8 T, effector memory proliferative natural killer (NK), CD160+ NK well tumor‐associated macrophages (TAMs) major histocompatibility complex‐II genes. a proportion naive CD4 Treg CD4, central CD8, TAMs immunomodulatory functions. Additionally, also observed that majority cancer‐associated fibroblasts (CAFs) AD, participated inflammation regulation, SCC‐derived CAFs similar functions cells, EMT hypoxia. This study revealed widespread reprogramming multiple populations dissected characteristics TME, proposed potential therapeutic strategies for CC, targeted therapy immunotherapy.
Язык: Английский
Процитировано
18
Nature reviews. Cancer, Год журнала: 2024, Номер 24(12), С. 850 - 866
Опубликована: Окт. 21, 2024
Язык: Английский
Процитировано
9
Cancer Cell International, Год журнала: 2024, Номер 24(1)
Опубликована: Апрель 22, 2024
Abstract The relationship between the immune cell and tumor occurrence progression remains unclear. Profiling alterations in microenvironment (TIME) at high resolution is crucial to identify factors influencing cancer enhance effectiveness of immunotherapy. However, traditional sequencing methods, including bulk RNA sequencing, exhibit varying degrees masking cellular heterogeneity immunophenotypic changes observed early late-stage tumors. Single-cell (scRNA-seq) has provided significant precise TIME landscapes. Consequently, this review highlighted molecular tumorigenesis elucidated through recent scRNA-seq studies. Specifically, we have summarized different stages, early, late, metastatic stages. Moreover, outlined related variations that may promote metastasis single-cell era. widespread applications will comprehensively redefine understanding biology furnish more effective immunotherapy strategies.
Язык: Английский
Процитировано
7
Environmental Toxicology, Год журнала: 2025, Номер unknown
Опубликована: Янв. 31, 2025
Abstract Background Cervical squamous cell carcinoma (CSCC) threatens the body health of women worldwide. This study aimed to foster a new concept prognostic indicator named death index (CDI). Methods RNA‐seq and scRNA‐seq datasets were downloaded from GEO TCGA database as training validation cohorts. Programmed (PCD)‐related gene signatures obtained published research. The construction model was performed based on CDI value. Patients with CSCC divided into high‐ low‐CDI groups. We explored differences in overall survival time, immune infiltration, mutation status, drug sensitivity between high low groups by R software. Results constructed calculate value 23 genes. have shorter time than those CDI. considered risk factor compared other characteristics. nomogram estimated (OS) at 1, 3, 6 years, age, Stage, CDI, indicating accuracy predicting 1‐, 3‐, 6‐year rates. values negatively correlated most checkpoint measured significant Mitoxantrone, Sabutoclax, Sepantronium bromide, Topotecan, BI‐2536, BMS‐754807 correlation. Conclusion investigation novel effective patients identified potential genes associated that could be targeted for prognosis treatment CSCC.
Язык: Английский
Процитировано
1
EBioMedicine, Год журнала: 2023, Номер 97, С. 104846 - 104846
Опубликована: Окт. 24, 2023
Cervical squamous cell carcinoma (CSCC) and adenocarcinoma (CAde) are two major pathological types of cervical cancer (CC), but their high-resolution heterogeneity tumor immune microenvironment remains elusive. Here, we performed single-nucleus RNA sequencing (snRNA-seq) from five CSCC three CAde samples, systematically outlined specific transcriptome atlas. We found CD8+ T cells in were more cytotoxic lower exhausted compared to those CAde, phagocytic MRC1+ macrophages specifically enriched CSCC. Interestingly, discovered that pro-tumoral cancer-associated myofibroblasts (myoCAFs) vascular-fibroblasts (vCAFs) abundant CSCC, further verified pro-metastatic roles vitro. Furthermore, also identified some chemotherapy drugs for (Dasatinib Doramapimod) (Pyrimethamine Lapatinib) by revealing transcriptomic profiles malignant epithelial cells, sensitivity lines constructed CC-derived organoids. Cell-cell communication networks revealed the pathways NRG1-ERBB2, FN1-ITAG3 respectively, which may partly explain specificities drugs. Our study described cellular interactions between could provide insights uncovering pathogenesis designing personalized treatment. National Key R&D Program China (2021YFC2701201), Natural Science Foundation (82072895, 82141106, 82103134, 81903114).
Язык: Английский
Процитировано
14
Experimental Cell Research, Год журнала: 2024, Номер 435(2), С. 113933 - 113933
Опубликована: Фев. 1, 2024
Язык: Английский
Процитировано
6
Nature Communications, Год журнала: 2024, Номер 15(1)
Опубликована: Ноя. 22, 2024
Although the incidence of cervical cancer (CC) has been reduced in high-income countries due to human papillomavirus (HPV) vaccination and screening strategies, it remains a significant public health issue that poses threat women's low-income countries. Here, we perform comprehensive proteogenomic profiling CC tumors obtained from 139 Chinese women. Integrated analysis links genetic aberrations downstream pathogenesis-related pathways reveals landscape HPV-associated multi-omic changes. EP300 is found enhance acetylation FOSL2-K222, consequently accelerating malignant proliferation cells. Proteomic stratification identifies three patient subgroups with distinct features prognosis, alterations, immune infiltration, post-translational modification regulations. PRKCB further identified as potential radioresponse-related biomarker patients. This study provides valuable resource for researchers clinicians delve into molecular basis CC, identify treatments ultimately advance clinical practice. Cervical problem many regions. authors patients; they reveal proteomic associated biological features, response radiotherapy.
Язык: Английский
Процитировано
6
Cancer Letters, Год журнала: 2023, Номер 576, С. 216408 - 216408
Опубликована: Сен. 26, 2023
Cervical cancer is now the fourth most prevalent malignancy in women worldwide, representing a tremendous burden of cancer. The heterogeneity complex tumor ecosystem impacts tumorigenesis, malignant progression, and response to treatment; thus, thorough understanding vital for enhancing prognosis patients with cervical rapid development widespread use single-cell sequencing have generated new paradigm research, providing comprehensive in-depth cancers. In this review, we give an overview recent advances made by leveraging studies dissection heterogeneity. We highlight evolution during initiation, treatment. High-resolution at level has potential drive targeted therapies enable realization personalized medicine.
Язык: Английский
Процитировано
13
BMC Cancer, Год журнала: 2023, Номер 23(1)
Опубликована: Окт. 18, 2023
Immunosuppression is a significant factor contributing to the poor prognosis of cancer. S100P, member S100 protein family, has been implicated in various cancers. However, its role tumor microenvironment (TME) pancreatic cancer remains unclear. This study aimed investigate potential impact S100P on TME characteristics patients with cancer.Multiple data (including microarray, RNA-Seq, and scRNA-Seq) were obtained from public databases. The expression pattern was comprehensively evaluated RNA-Seq validated four different microarray datasets. Prognostic value assessed through Kaplan-Meier plotter Cox regression analyses. Immune infiltration levels determined using ESTIMATE ssGSEA algorithms at single-cell level. Spearman correlation test used examine between immune checkpoint genes, mutation burden (TMB). DNA methylation analysis performed change mRNA expression. Reverse transcription PCR (RT-PCR) immunohistochemical (IHC) utilized validate five cell lines 60 tissues.This found that differentially expressed associated (P < 0.05). Notably, exhibited negative-correlation infiltration, particularly CD8 + T cells. Furthermore, close association immunotherapy observed, as it strongly correlated TMB TIGIT, HAVCR2, CTLA4, BTLA Intriguingly, higher demonstrated negative (cg14323984, cg27027375, cg14900031, cg14140379, cg25083732, cg07210669, cg26233331, cg22266967), which In vitro RT-PCR upregulated across all lines, IHC confirmed high tissues 0.05).These findings suggest could serve promising biomarker for immunosuppressive microenvironment, may provide novel therapeutic way
Язык: Английский
Процитировано
12
Frontiers in Immunology, Год журнала: 2024, Номер 15
Опубликована: Фев. 8, 2024
Objective Many patients treated with immune checkpoint inhibitors (ICIs) developed primary or secondary drug resistance for unknown reasons. This study investigates whether mismatch repair (MMR) genes are responsible this therapeutic restriction. Methods We obtained the transcriptional, clinical and single nucleotide polymorphism data endometrial cancer (EC) from The Cancer Genome Atlas immunophenoscore of EC Immunome Atlas, then analyzed in R to evaluate relationship between MMR clinicopathological features, prognosis, infiltration, expression responsiveness ICIs EC. used differentially expressed MSH6 high low groups conduct GO KEGG analyses explore impact on biological functions Finally, we verified bioinformatics results vitro experiments. Results Our showed that compared group, group had better survival outcomes less aggressive features. In multivariate Cox analysis, was only independent risk factor could predict prognosis Besides, also a higher score, more active infiltration expression, resulting treatment, consistent enrichment terms pathways related response group. Meanwhile, were associated cell cycle, DNA damage tumorigenesis. To exclude influence mutations, performed previous wild-type tumor samples results. experiments confirmed after knocking down cells, their proliferation, migration invasion abilities weakened, while levels PD-L1 PD-L2 elevated. comparison, overexpression an opposite trend. Conclusion Reduced serve as potential biomarker predicting status, level treatment may become target treating solid tumors.
Язык: Английский
Процитировано
5