Treatment outcome of disseminated nodule resection for peritoneal metastasis from colorectal cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer
PROVIDER: 2650865 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:When disseminated into the peritoneal cavity at the very early stage, cancer cells must adapt to the glucose- and oxygen-limited environment in peritoneal fluid, yet the key molecular regulators remain undefined. Here, we reveal that early disseminated OC cells are ingeniously utilize hyaluronic acid as an energy source and a signal molecule to survive in the nutrient-limited peritoneal microenvironment. Through a genome-wide CRISPR/Cas9 knockout screening in an orthotopic ovarian cancer (OC) model, we identified a series of genes involved in hyaluronic acid (HA) catabolism and glucuronic acid (GlcA) metabolism, including the HA receptor LAYN, HA catabolism enzymes (including HYAL1 and HYAL3) and key GlcA metabolic enzymes (such as AKR1A1 and XYLB). By integrating transcriptomic and metabolic analyses in multiple experimental systems, we demonstrated that HA induced the expression of key HA catabolism and GlcA pathway enzymes, which further led to the release of free GlcA from HA degradation. This GlcA is subsequently metabolized through the GlcA pathway, the pentose phosphate pathway (PPP) and glycolysis to support the maintenance and growth of disseminated OC cells. In addition, we found an atypical Rho GTPase RHOU facilitated the LAYN endosomal recycling for efficient HA uptake. Intriguingly, the rewiring of HA catabolism through GlcA pathway was regulated by its classical receptor CD44 and occurred in other peritoneal disseminating cancers such as bladder cancer and pancreatic adenocarcinoma. This signaling-metabolic axis demonstrates the dual role of HA as both a signaling molecule and an energy source supporting cancer cells survival. Importantly, pharmacological inhibition of HYAL1 with garcinol potently suppressed peritoneal disseminated metastasis in xenograft mice and synergized with cisplatin. In this study, we collectively reported a novel HA-induced metabolic reprogramming feature of the early peritoneal disseminated cancer cells, which provides new diagnostic and therapeutic strategies for the cancers prone to the potential dissemination.
2026-07-10 | MTBLS15007 | MetaboLights
Project description:Peritoneal metastasis evolution
| PRJNA1139881 | ENA
Project description:Peritoneal metastasis evolution
| PRJNA1139882 | ENA
Project description:Pancreatic ductal adenocarcinoma (PDAC) frequently metastasizes into the peritoneum, which contributes to poor prognosis. Metastatic spreading is promoted by cancer cell plasticity, yet its regulation by the microenvironment is incompletely understood. Here, we show that the presence of hyaluronan and proteoglycan link protein-1 (HAPLN1) in the extracellular matrix enhances tumor cell plasticity and PDAC metastasis. Bioinformatic analysis showed that HAPLN1 expression is enriched in the basal PDAC subtype and associated with worse overall patient survival. In a mouse model for peritoneal carcinomatosis, HAPLN1-induced immunomodulation favored a more permissive microenvironment, which accelerated the peritoneal spread of tumor cells. Mechanistically, HAPLN1, via upregulation of tumor necrosis factor receptor 2 (TNFR2), promoted TNF-mediated upregulation of Hyaluronan (HA) production, facilitating EMT, stemness, invasion and immunomodulation. Extracellular HAPLN1 modified cancer cells and fibroblasts, rendering them more immunomodulatory. As such, we identified HAPLN1 as a prognostic marker and as a driver for peritoneal metastasis in PDAC.
2023-03-31 | GSE211126 | GEO
Project description:HAPLN1 potentiates peritoneal metastasis in pancreatic cancer
| PRJNA869049 | ENA
Project description:Triple-Negative Breast Cancer (TNBC) has a poor prognosis and adverse clinical outcomes among all breast cancer subtypes as there is no available targeted therapy. Overexpression of Enhancer of zeste homolog 2 (EZH2) has been shown to correlate with TNBC's poor prognosis, but the contribution of EZH2 catalytic (H3K27me3) versus non-catalytic EZH2 (NC-EZH2) function in TNBC progression remains elusive. We reveal that selective hyper-activation of functional EZH2 (H3K27me3) over NC-EZH2 alters TNBC metastatic landscape and fosters its peritoneal metastasis, particularly splenic. Instead of H3K27me3-mediated repression of gene expression; here, it promotes KRT14 transcription by attenuating binding of repressor Sp1 to its promoter. Further, KRT14 loss significantly reduces TNBC migration, invasion, and peritoneal metastasis. Consistently, human TNBC metastasis displays positive correlation between H3K27me3 and KRT14 levels. Finally, EZH2 knockdown or H3K27me3 inhibition by EPZ6438 reduces TNBC peritoneal metastasis. Altogether, our preclinical findings suggest a rationale for targeting TNBC with EZH2 inhibitors.
2022-11-10 | GSE217474 | GEO
Project description:10X Next GEM Single Cell 5’ Kit v2 scRNAseq of maximum 15 000 sorted CD127+ ILCs (CD45+, CD3-, CD19-, Lin- and CD127+), NK cells (CD45+, CD3-, CD19-, Lin-, CD94+/- and CD56+) and non-conventional (nc)ILCs (CD45+, CD3-, CD19-, Lin-, CD94+/-, CD56- and CD7+) per sample from 11 patients. Total of 4 paired healthy colon and colorectal cancer tumours, 2 paired healthy colon, colorectal cancer tumours and peritoneal metastasis and 5 unpaired peritoneal metastasis.
2026-02-11 | GSE302045 | GEO
Project description:EZH2-H3K27me3 mediated KRT14 upregulation promotes TNBC peritoneal metastasis
| PRJNA899075 | ENA
Project description:Gastric cancer (GC) remains one of the most prevalent tumor worldwide, and ranks third in cancer-related deaths globally. Long non-coding RNAs (lncRNAs) have been reported to play significant role in the progression and metastasis in gastric cancer (GC), however, the molecular mechanism are largely elusive. We aim to identify up-regulated lncRNA in gastric cancer peritoneal metastasis and study their function in promoting tumor progression and metastasis.
2025-04-01 | GSE200697 | GEO
Project description:In this study we aimed to analyze the biological mechanisms underlying apparently different modes of peritoneal tumor spread in serous ovarian cancer: miliary (widespread, millet-like lesions) versus non-miliary (bigger, exophytically growing implants). Tumor tissues and ascites from 23 chemotherapy naive patients were analyzed by RNA-sequencing and flow cytometry. On the basis of differential gene expression between miliary and non-miliary, gene signatures were developed. A calculated tumor spread factor revealed a significant independent negative impact of miliary spread on overall survival (HR 3.77; CI95 1.14–12.39; p = 0.029) in an independent cohort of 165 serous ovarian cancer patients. Comparing previously published epithelial-mesenchymal transition (EMT) gene signatures, non-miliary spread correlated significantly with a reduced epithelial status. We conclude that serous ovarian cancer is a heterogeneous disease with distinct modes of peritoneal tumor spread, differing not only in clinical appearance, but also in molecular characteristics and outcome. EMT, peritoneal inflammation status, and therapeutic options are discussed. Significance: More than half of serous epithelial ovarian cancer patients present with a newly described type of intraperitoneal tumor spread, associated with differences in the inflammation status, activated oncogenic pathways, lack of EMT, and thus reduced overall survival. Both, the diminished immune reaction and the enhanced epithelial and malignant characteristics of the tumor cells open new avenues for therapeutic options and strategies, like Catumaxomab, already in clinical use.
2025-04-03 | GSE293643 | GEO