ArticleCancers2021
Geospatial Cellular Distribution of Cancer-Associated Fibroblasts Significantly Impacts Clinical Outcomes in Metastatic Clear Cell Renal Cell Carcinoma.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Anti-FAP CAR-NK cells as a novel targeted therapy against cervical cancer and cancer-associated fibroblasts.Oncoimmunology · 2025Article
- The role of cancer-associated fibroblasts in the tumour microenvironment of urinary system.Clinical and translational medicine · 2025Review
- Recent progress on tyrosine kinase inhibitors resistance in renal cell carcinoma: another brick in the wall?Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Increased spatial coupling of integrin and collagen IV in the immunoresistant clear-cell renal-cell carcinoma tumor microenvironment.Genome biology · 2024Article
- Integration of bulk RNA-seq and single-cell RNA-seq constructs: a cancer-associated fibroblasts-related signature to predict prognosis and therapeutic response in clear cell renal cell carcinoma.American journal of translational research · 2024Article
- Distinguishing Keratoacanthoma from Well-Differentiated Cutaneous Squamous Cell Carcinoma Using Single-Cell Spatial Pathology.The Journal of investigative dermatology · 2023Article
- Increased spatial coupling of integrin and collagen IV in the immunoresistant clear cell renal cell carcinoma tumor microenvironment.bioRxiv : the preprint server for biology · 2023Article
- Stroma-Mediated Breast Cancer Cell Proliferation Indirectly Drives Chemoresistance by Accelerating Tumor Recovery between Chemotherapy Cycles.Cancer research · 2023Article
- Heterogeneity and function of cancer-associated fibroblasts in renal cell carcinoma.Journal of the National Cancer Center · 2023Article
- Effective dose window for containing tumor burden under tolerable level.NPJ systems biology and applications · 2023Article
- Impact of radiopharmaceutical therapy (EJNMMI physics · 2022Article
- Assessment of the prognostic value ofTranslational andrology and urology · 2022Article
- The impact of the spatial heterogeneity of resistant cells and fibroblasts on treatment response.PLoS computational biology · 2022Article
- Single-cell transcriptomics reveals a low CD8Journal for immunotherapy of cancer · 2022Article
- Review
- Association of Systemic Inflammation and Overall Survival in Elderly Patients with Cancer Cachexia - Results from a Multicenter Study.Journal of inflammation research · 2021Article
- Research Progress of Tumor Microenvironment Targeted Therapy for Clear Cell Renal Cell Carcinoma.Cancer control : journal of the Moffitt Cancer CenterReview
Corrections and comments
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Authors and funding
21 authors at 1 institution in 1 country.
Funding
Abstract
Cancer-associated fibroblasts (CAF) are highly prevalent cells in the tumor microenvironment in clear cell renal cell carcinoma (ccRCC). CAFs exhibit a pro-tumor effect in vitro and have been implicated in tumor cell proliferation, metastasis, and treatment resistance. Our objective is to analyze the geospatial distribution of CAFs with proliferating and apoptotic tumor cells in the ccRCC tumor microenvironment and determine associations with survival and systemic treatment. Pre-treatment primary tumor samples were collected from 96 patients with metastatic ccRCC. Three adjacent slices were obtained from 2 tumor-core regions of interest (ROI) per patient, and immunohistochemistry (IHC) staining was performed for αSMA, Ki-67, and caspase-3 to detect CAFs, proliferating cells, and apoptotic cells, respectively. H-scores and cellular density were generated for each marker. ROIs were aligned, and spatial point patterns were generated, which were then used to perform spatial analyses using a normalized Ripley's K function at a radius of 25 μm (nK(25)). The survival analyses used an optimal cut-point method, maximizing the log-rank statistic, to stratify the IHC-derived metrics into high and low groups. Multivariable Cox regression analyses were performed accounting for age and International Metastatic RCC Database Consortium (IMDC) risk category. Survival outcomes included overall survival (OS) from the date of diagnosis, OS from the date of immunotherapy initiation (OS-IT), and OS from the date of targeted therapy initiation (OS-TT). Therapy resistance was defined as progression-free survival (PFS) <6 months, and therapy response was defined as PFS >9 months. CAFs exhibited higher cellular clustering with Ki-67
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.