Biological Heterogeneity of Chondrosarcoma: From (Epi) Genetics through Stemness and Deregulated Signaling to Immunophenotype

Zając, Agnieszka; Król, Sylwia; Rutkowski, Piotr; Czarnecka, Anna M.

doi:10.3390/cancers13061317

Cited by 13 publications

(10 citation statements)

References 164 publications

(283 reference statements)

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“…At least 460 distinct COL2A1 mutations, 663 distinct probands, and 21 illnesses have been identi ed so far 20 . One of the most often altered genes that contribute to the development of chondrosarcoma is COL2A1 21 . COL2A1 was a risk factor in our model as a result.…”

Section: Discussionmentioning

confidence: 99%

A novel defined basement membrane-related genes signature for predicting the prognosis of Hepatocellular carcinoma

Luo¹,

Zhang

Yang

2023

Preprint

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Background. Hepatocellular carcinoma (HCC) is a highly heterogeneous disease with poor prognosis, making the prediction of the prognosis much challenges. Basement membrane-related genes (BMRGs) play an important role in the progression of cancer. Thus, they are often used as targets to inhibit tumor progression. However, the value of BMRGs in predicting prognosis of HCC still remains to be further elucidated. This study aimed to find the relationship between BMRGs and HCC and the value of BMRGs in predicting the prognosis of HCC. Methods. We acquired transcriptome and clinical data of HCC from The Cancer Genome Atlas (TCGA) and randomly divided the data into training and test sets in order to develop a reliable prognostic signature of BMRGs for HCC. The BMRGs model was built using multivariate Cox regression, least absolute shrinkage and selection operator (LASSO), and univariate Cox regression. The risk signature was further validated and assessed using the principal component analysis (PCA), Kaplan-Meier analysis, and time-dependent receiver operating characteristics (ROC). To forecast the overall survival, a nomogram and calibration curves were created (OS). Functional enrichment analysis was used to evaluate the potential biological pathways. We also conducted immunological research and a pharmacological comparison between the high- and low-risk groups in this study. Results. We identified 16 differentially expressed genes and constructed a risk model of four BMRGs, including COL2A1, CTSA, LAMB1,P3H1. The PCA analysis showed that the signature could distinguish the high- and low-risk groups well. Patients in the low-risk group showed significantly better outcome compared with patients in the high-risk group. Receiver operating characteristic (ROC) curve analysis show predictive capacity. Moreover, the nomogram showed good predictability. Univariate and multivariate Cox regression analysis validated that the model results supported the hypothesis that BMRGs were independent risk factors for HCC. Furthermore, analysis of clinical characteristics and tumor microenvironment (TME) between risk groups showed significant difference. Functional analysis revealed different immune-related pathways were enriched, and immune status were different between two risk groups. Mediation analysis with IC50 revealed that the two risk group were significantly different, which could be a guidance of systemic treatment. Finally, we further verified in clinical samples that the mRNA and protein expression levels of the four genes in this model are significantly higher in liver cancer tissues than in adjacent tissues. Conclusion. A novel BMRGs signature can be used for prognostic prediction in HCC. This provide us with a potential progression trajectory as well as predictions of therapeutic response.

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Section: Discussionmentioning

confidence: 99%

A novel defined basement membrane-related genes signature for predicting the prognosis of Hepatocellular carcinoma

Luo¹,

Zhang

Yang

2023

Preprint

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“…M1‐type macrophages demonstrate a proclivity for secreting inflammatory cytokines, thereby exerting anti‐tumour effects. In contrast, M2‐type macrophages, characterized by their secretion of anti‐tumour cytokines, paradoxically contribute to tumour progression 59 . Notably, within the TME, TAMs often exhibit a propensity for polarization towards the M2 type 59 .…”

Section: Engineered Exosomes For Immunomodulation In Bcmentioning

confidence: 99%

Engineering exosomes to reshape the immune microenvironment in breast cancer: Molecular insights and therapeutic opportunities

Cao,

Lv,

Wei

2024

Clinical & Translational Med

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BackgroundBreast cancer remains a global health challenge, necessitating innovative therapeutic approaches. Immunomodulation and immunotherapy have emerged as promising strategies for breast cancer treatment. Engineered exosomes are the sort of exosomes modified with surface decoration and internal therapeutic molecules. Through suitable modifications, engineered exosomes exhibit the capability to overcome the limitations associated with traditional therapeutic approaches. This ability opens up novel avenues for the development of more effective, personalized, and minimally invasive interventions.Main bodyIn this comprehensive review, we explore the molecular insights and therapeutic potential of engineered exosomes in breast cancer. We discuss the strategies employed for exosome engineering and delve into their molecular mechanisms in reshaping the immune microenvironment of breast cancer.ConclusionsBy elucidating the contribution of engineered exosomes to breast cancer immunomodulation, this review underscores the transformative potential of this emerging field for improving breast cancer therapy.Highlights Surface modification of exosomes can improve the targeting specificity. The engineered exosome‐loaded immunomodulatory cargo regulates the tumour immune microenvironment. Engineered exosomes are involved in the immune regulation of breast cancer.

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“…Chondrosarcoma tumor tissue, like hyaline, is characterized by a dense ECM with poor blood and lymph vascularity, on which a low percentage of dividing cells is embedded. Thus, the ECM forms a physical semi-permeable barrier, inhibiting cytotoxic agents reaching their target, i.e., chondrosarcoma cells, while reduced blood circulation creates severe chronichypoxia [116]. Moreover, the Schwan chondrosarcoma ECM disturbance by modifying the synthesis of ECM components, mainly PGs, attenuates this tumor growth [117].…”

Section: The Non-cellular Tme Compartment In Sarcomasmentioning

confidence: 99%

The Role of IGF/IGF-IR-Signaling and Extracellular Matrix Effectors in Bone Sarcoma Pathogenesis

Tzanakakis

Giatagana

Berdiaki

et al. 2021

Cancers

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Bone sarcomas, mesenchymal origin tumors, represent a substantial group of varying neoplasms of a distinct entity. Bone sarcoma patients show a limited response or do not respond to chemotherapy. Notably, developing efficient chemotherapy approaches, dealing with chemoresistance, and preventing metastasis pose unmet challenges in sarcoma therapy. Insulin-like growth factors 1 and 2 (IGF-1 and -2) and their respective receptors are a multifactorial system that significantly contributes to bone sarcoma pathogenesis. Whereas failures have been registered in creating novel targeted therapeutics aiming at the IGF pathway, new agent development should continue, evaluating combinatorial strategies for enhancing antitumor responses and better classifying the patients that could best benefit from these therapies. A plausible approach for developing a combinatorial strategy is to focus on the tumor microenvironment (TME) and processes executed therein. Herewith, we will discuss how the interplay between IGF-signaling and the TME constituents affects sarcomas’ basal functions and their response to therapy. This review highlights key studies focusing on IGF signaling in bone sarcomas, specifically studies underscoring novel properties that make this system an attractive therapeutic target and identifies new relationships that may be exploited. Potential direct and adjunct therapeutical implications of the extracellular matrix (ECM) effectors will also be summarized.

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Biological Heterogeneity of Chondrosarcoma: From (Epi) Genetics through Stemness and Deregulated Signaling to Immunophenotype

Cited by 13 publications

References 164 publications

A novel defined basement membrane-related genes signature for predicting the prognosis of Hepatocellular carcinoma

A novel defined basement membrane-related genes signature for predicting the prognosis of Hepatocellular carcinoma

Engineering exosomes to reshape the immune microenvironment in breast cancer: Molecular insights and therapeutic opportunities

The Role of IGF/IGF-IR-Signaling and Extracellular Matrix Effectors in Bone Sarcoma Pathogenesis

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