HYAL1 (Hyaluronidase 1)

Future research must decipher HYAL1's context-specific roles within tumor heterogeneity, elucidate its epigenetic regulation, and develop targeted strategies. A deeper understanding of this HYAL1 paradox is essential to leverage its potential for precision cancer therapies targeting HA metabolism.

Our findings suggest that stromal cells may contribute to the radioresistant tumor microenvironment in PCa partly through alterations in high-molecular-weight HA. While targeting HA metabolism holds potential to improve the efficacy of RT by disrupting this protective niche, further studies are needed to clarify the underlying mechanisms and validate these effects in vivo.

Drug enrichment analysis predicted potential therapeutic compounds, especially sunitinib targeting LRRK2...The diagnostic model based on the six ExoNSCLC-DEGs has strong diagnostic performance and clinical applicability. In-depth research on ExoNSCLC-DEGs provides new insights into the pathogenesis of NSCLC and provides new directions for subsequent research.

This study unveils the expression characteristics and biological significance of exosome-associated genes in lung cancer. The differential expression of these genes not only offers potential biomarkers for early diagnosis of lung cancer but also lays a foundation for further research into their biological functions in this disease.

HAS1 and HYAL2 were identified as novel prognostic biomarkers. These findings provide new insights into HA metabolism in RCC and open potential avenues for better understanding and management of these tumors.

Our analysis demonstrates that succinylation-related molecular activities display distinct expression patterns across cancers, which are associated with metabolic regulation, immune modulation, and disease prognosis. The succinylation-based prognostic model provides a novel risk stratification tool for CRC, while PCED1A-dependent succinylation regulation may serve as a potential therapeutic target.

Eight genes were identified as associated with CRC, among which DBI exhibited a potential protective role, correlating with improved patient survival, enhanced immune activation, and increased responsiveness to immunotherapy. The remaining proteins demonstrated diverse and complex functions within the tumor immune microenvironment, providing novel insights for the development of precision diagnostics and immunotherapeutic strategies.

In addition, in vitro analyses revealed that lower molecular weight HA increased sphere forming ability and migration in MCF-7 and MDA-MB-231, whereas higher molecular weight HA inhibited them. It was concluded that HA needs to be degraded by HYAL2 to exert pro-tumorigenic effects and comprehensive HA/HYAL2 status serves as a potent prognostic factor in breast cancer.

WNT5B expression is high in osteosarcoma stem cells leading to increased stem cell proliferation and migration through SOX2. WNT5B expression in stem cells increases rates of osteosarcoma metastasis to the lungs and liver in vivo. The hyaluronic acid degradation enzyme HYAL1 is regulated by WNT5B in osteosarcoma contributing to metastasis. Inhibition of WNT5B with a ROR1 antibody decreases osteosarcoma stemness.

OVV-Hyal1 effectively degrades HA to reshape the TME, therefore overcoming some major hurdles in current cancer therapy, such as limited OVs spread, unfavored dissemination of chemo drugs, polypeptides, antibodies, and insufficient infiltration of effector immune cells. OVV-Hyal1 holds the promise to improve the antitumor outcomes of current cancer therapeutics.

MAC-related genes were able to classify CRC. A RiskScore signature based on the colorectal MAC-related molecular subtype was constructed, which had important clinical significance for guiding the accurate stratification of CRC patients.

We found that HYAL1 interacted with AURKB and further activated the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in macrophages. In conclusion, ESCC-derived exosomes containing HYAL1 facilitate M2 macrophage polarization by targeting AURKB to active the PI3K/AKT signaling pathway, which in turn promotes ESCC progression.