Six Gasdermins (GSDM) family members participate in various biological processes especially pyroptosis, as well as in the initiation and development of many types of cancer. However, the systematic analysis of the GSDM family in hepatocellular carcinoma (HCC) is lacking. In this study, several bioinformatics databases were recruited to analyze the roles of the GSDMs in differential expression, prognostic correlation, functional enrichment exploration, immune modulation, genetic alterations, and methylated modification in patients with HCC. Consequently, the mRNA expression of all the six GSDMs was accordantly increased in HCC, while only the protein expressions of GSDMB, GSDMD, and GSDME were apparently increased in HCC tissue. The expression of all the GSDMs (except GSDMA) was significantly higher in tumor stage 1-3 subgroups, compared with that in normal subgroups. Higher GSDME expression was significantly associated with shorter overall survival (OS) and disease specific survival (DSS) in patients with HCC. GSDMD had the highest genetic alteration rate among the GSDMs. The three signal pathways which were most likely related to GSDMs-associated molecules were the cell adhesion, growth regulation, and hormone metabolic process. The majority of GSDMs members were positively correlated with the infiltration of B cells, neutrophils, and dendritic cells, however negatively correlated with macrophage. All of the six GSDM members showed remarkably decreased methylation levels in HCC tissues. In conclusion, the GSDM family (especially GSDME) had the potential to become essential biomarkers to better improve the diagnosis and prognosis of HCC, as well as provided insight for the development of therapeutic targets.

Ultrasound-responsive nanomaterials represent a cutting-edge approach to cancer immunotherapy. Their emergence has unlocked novel capabilities in targeted drug delivery and immune modulation, offering unparalleled advantages for optimizing treatment outcomes. This review primarily discusses the application potential of ultrasound-responsive nanosystems in antitumor immunity, highlighting their ability to accelerate immunogenic cell death (ICD) and modulate the tumor microenvironment (TME). These nanocarriers exhibit remarkable efficacy in transporting therapeutic agents directly to tumor sites under ultrasound guidance, thereby increasing the specificity and efficacy of treatment. Additionally, this review explores the unique biological stability and drug delivery capabilities of ultrasound-responsive nanomaterials, which are essential for their clinical application. In the context of immune imaging, these nanomaterials can potentially monitor therapeutic responses in real time, offering a visual understanding of treatment effectiveness and patient prognosis. Ultimately, fully realizing the translational potential of ultrasound-responsive nanomaterials in anticancer immunity will help pave the way for personalized and effective cancer management.

Background:Ovarian cancer (OV) is one of the common malignant tumors and has a poor prognosis. Chromobox (CBX) family proteins are critical components of epigenetic regulation complexes that repress target genes transcriptionallyviachromatin modification. Some studies have investigated the function specifications among several CBXs members in multiple cancer types, however, little is known about the functions and prognostic roles of distinct CBXs family proteins in ovarian cancer.Methods:In this study, several bioinformatics databases andin vitroexperiments were used to analyze the expression profiles, prognostic values, and therapeutic potential of the CBXs family (CBX1-8) in ovarian cancer.Results:It was found that higher expression of CBX3/8 and lower expression of CBX1/6/7 were detected in OV tissues. CBX2/4/5/8 were significantly correlated with individual cancer stages of OV. The expression of CBX1/2/3 were all significantly associated with worse overall survival (OS) and progression-free survival (PFS) for OV patients, whereas the expression of other five CBXs members showed either irrelevant (CBX5 and CBX8) or inconsistent (CBX4, CBX6, and CBX7) results for both OS and PFS in OV. These results showed that only CBX3 had consistent results in expression and prognosis. Further cell experiments also showed that CBX3 promoted the proliferation of ovarian cancer cells. CBX3 was highly expressed in chemoresistant OV tissues. These results indicated that CBX3 was the most likely prognostic indicator and new therapeutic target in OV. Furthermore, gene enrichment analysis suggests that the CBXs family was primarily involved in mast cell activation and mast cell mediated immunity. Individual CBXs members were associated with varying degrees of the infiltration of immune cells, especially B cells. Finally, a high genetic alteration rate of CBXs family (39%) was observed in OV. The low methylation status of CBX3/8 in OV may be associated with their high expression levels.Conclusions:Taken together, these findings exhibited the pivotal value of CBXs family members (especially CBX3) in the prognosis and chemoresistance of ovarian cancer. Our results may provide new insight to explore new prognostic biomarkers and therapeutic targets for ovarian cancer.

Background. Ovarian cancer (OC) seriously threatens womens life. Ferroptosis plays an essential role in the initiation and development of OC. However, more molecular targets and mechanisms for ferroptosis in OC remain to be further elucidated. Methods. Several OC datasets were integrated in this study and three candidate genes including PRNP were further screened out as the ferroptosis-related gene which was differentially expressed in OC. Then, comprehensive evaluations concerning gene expression, clinical implication, in vitro validation of expression and functional experiments, prediction of downstream molecules and related signal pathways, and immune-modulating function were performed. Results. PRNP was the only downregulated ferroptosis-related gene with prognostic value for OC patients. The decreased mRNA and protein expression was verified in OC tissues and cell lines. PRNP was significantly correlated with cancer stages, primary therapy outcomes, and age in OC patients. Moreover, we found that overexpression of PRNP inhibited the proliferation, migration, and invasion ability of OC cells through in vitro experiments. PRNP was enriched to the Ras signaling pathway. PRNP expression was positively correlated with the infiltration of immune cells, such as mast cells, T effector memory cells, plasmacytoid DC cells, NK cells, and eosinophils. In addition, the association of PRNP with other immune signatures was also found. Conclusion. This study demonstrated for the first time showed that ferroptosis-related gene PRNP exerted a tumor suppressive role in OC and the aberrant expression and function of PRNP making it a potential novel biomarker for OC diagnosis, prognosis, and response to immunotherapies.

CCN gene family members have recently been identified as multifunctional regulators involved in diverse biological functions, especially in vascular and skeletal development. In the present study, a comparative genomic and phylogenetic analysis was performed to show the similarities and differences in structure and function of CCNs from different organisms and to reveal their potential evolutionary relationship. First, CCN homologs of metazoans from different species were identified. Then we made multiple sequence alignments, MEME analysis, and functional sites prediction, which show the highly conserved structural features among CCN metazoans. The phylogenetic tree was further established, and thus CCNs were found undergoing extensive lineage-specific duplication events and lineage-specific expansion during the evolutionary process. Besides, comparative analysis about the genomic organization and chromosomal CCN gene surrounding indicated a clear orthologous relationship among these species counterparts. At last, based on these research results above, a potential evolutionary scenario was generated to overview the origin and evolution of the CCN gene family.

Background. All YTH domain family members are m⁶A reader proteins accounting for the methylation modulation involved in the process of tumorgenesis and tumor progression. However, the expression profiles and roles of the YTH domain family in lung adenocarcinoma (LUAD) remain to be further illustrated. Methods. GEPIA2 and TNMplot databases were used to generate the expression profiles of the YTH family. Kaplan-Meier plotter database was employed to analysis the prognostic value of the YTH family. Coexpression profiles and genetic alterations analysis of the YTH family were undertaken using the cBioPortal database. YTH family protein-associated protein-protein interaction (PPI) network was identified by using STRING. Functional enrichment analysis was performed with the help of the WebGestalt database. The correlation analysis between the YTH family and immune cell infiltration in LUAD was administrated by using the TIMER2.0 database. Results. mRNA expression of YTHDC1 and YTHDC2 was significantly lower in LUAD, whereas YTHDF1, YTHDF2, and YTHDF3 with apparently higher expression. YTHDF2 expression was observed to be the highest in the nonsmoker subgroup, and its expression gradually decreased with the increased severity of smoking habit. LUAD patients with low expression of YTHDC2, YTHDF1, and YTHDF2 were correlated with a better overall survival (OS) time. The YTHDF1 genetic alteration rate was 26, which was the highest in the YTH family. The major cancer-associated functions of YTH family pointed in the direction of immunomodulation, especially antigen processing and presentation. Most of the YTH family members were significantly correlated with the infiltration of CD4+ T cells, CD8+ T cells, macrophages, and neutrophils, indicating the deep involvement of the YTH domain family in the immune cell infiltration in LUAD. Conclusion. The molecular and expression profiles of the YTH family were dysregulated in LUAD. YTH family members (especially YTHDC2) were promising biomarkers and potential therapeutic targets that may bring benefit for the patients with LUAD.