Mesothelin (MSLN) is a glycoprotein with various expression degrees in different tumors including mesothelioma, ovarian cancer, pancreatic cancer, etc. MSLN is considered to play an important role in cell survival, proliferation, and tumor progression. Although the expression of MSLN in tumors makes it a potential therapeutic target, its mechanism of action is still unclear, especially its correlation with immune cells infiltration in the tumor microenvironment has not been investigated. In this study, we detected the overexpression of MSLN in ovarian cancer using database analysis and tissue-array staining. We further evaluated the diagnostic value of MSLN and found it was associated with poor overall survival in ovarian cancer. In addition, the high expression of MSLN was significantly related to the immune-related genes and chemoresistant genes. We confirmed the overexpression of MSLN in the chemoresistant ovarian cancer cell lines. Our research suggests that MSLN participates in a variety of pathways related to the suppression of immune activation and promotion of chemoresistance, leading to a poor prognosis in ovarian cancer.

Aldolase A (ALDOA) is an enzyme that plays an important role in glycolysis and gluconeogenesis, which is closely related to tumor metabolism. In this study, the overall roles of ALDOA in pan-cancer have been investigated from several aspects using databases and online analysis tools. Using the ONCOMINE database, the expression of ALDOA in various cancers was analyzed. The prognostic role of ALDOA was explored by PrognoScan, GEPIA, and Kaplan–Meier Plotter. The immune-related role of ALDOA and its downstream substrates was decided by TIMER, cBioPortal and String. Our data indicate that ALDOA expression level in lung adenocarcinoma, liver hepatocellular carcinoma, head and neck squamous cell carcinoma is higher than that in normal tissues. Increased expression of ALDOA often indicates a poor prognosis for patients. The correlation between ALDOA and immune infiltration among different tumors is very different. We also investigate the relationship between ALDOA and its upstream/downstream proteins. Our results showed that ALDOA could be used as a biomarker for the tumor prognosis, and could be correlated with the infiltrating levels of macrophages, CD4+ T cells and CD8+ T cells.

Lipid nanoparticles (LNPs)‐based mRNA vaccines have witnessed their great advantages in the fight against infectious diseases. However, the pro‐inflammatory properties of mRNA‐LNPs vaccines may hinder the induction of antigen‐specific tolerogenic immune responses. Here, it is demonstrated that stearic acid‐doped LNPs co‐loaded with nucleoside‐modified mRNA and celastrol selectively target spleen, convert their adjuvanticity and promote a tolerogenic rather than immunogenic DCs phenotype. Furthermore, the tolerogenic mRNA vaccine also invokes the generation of antigen‐specific regulatory T cells (Tregs) in the spleen and migration of the induced Tregs to the lung. In a mouse model of allergic asthma, immunization with the tolerogenic mRNA vaccine significantly alleviated symptom induction, reducing eosinophilic granulocyte accumulation and mucus secretion. In conclusion, this spleen‐targeted mRNA‐LNPs vaccine platform induces tolerogenic immune responses, offering promise for the development of therapeutics against allergic asthma and other conditions requiring immune tolerance modulation.

The polysaccharides MPSSS was extracted from Lentinus edodes and has been reported to effectively inhibit tumor growth and eliminate the function of myeloid-derived immune suppressor cell-mediated T cell inhibition, thus improving the efficacy of cancer therapy. The exploration of how MPSSS affects the functions of cancer-associated fibroblasts (CAFs) will provide a new perspective for understanding the antitumor effects of MPSSS. In the present study, prostate CAFs were selected as target cells to study whether MPSSS affected cell proliferation and function. The results showed that MPSSS did not directly inhibit the growth of prostate CAFs but interfered with CAF-mediated T cell inhibition and affected the immunosuppressive function of prostate CAFs. Mechanistic studies were further performed and showed that MPSSS activated key node proteins in the NF-κB pathway that were dependent on MyD88, and a TLR4 inhibitor blocked the changes in these proteins and the effect of MPSSS. We hypothesize that MPSSS can activate the MyD88-dependent TLR4-NF-κB signaling pathway to change the function of CAFs. In conclusion, these results demonstrate that MPSSS can not only effectively inhibit the growth of prostate cancer as we previously reported but also alter the function of prostate CAFs by activating the TLR4-NF-κB pathway, providing a new strategy for the comprehensive treatment of tumors.

Background: Radiotherapy is widely used in treating cervical cancer patients, however, radioresistance unavoidably occurs and seriously affects the treatment effect. It is well known that hypoxia plays an important role in promoting radioresistance in tumor microenvironment, yet our understanding of the effect of small extracellular vesicles miRNA on cervical cancer radiosensitivity in hypoxic environment is still limited. Methods: Small extracellular vesicles extracted from hypoxic and normoxic cultured cervical cancer cells were evaluated for their effects on radioresistance. miR-152-3p was found to be a potential effector in hypoxia-derived extracellular vesicles by searching the GEO database. Its downstream substrate was confirmed by double luciferase report, which was KLF15. The role of miR-152-3p and KLF15 in regulating cervical cancer radioresistance was detected by cell activity assays. The findings were confirmed in vivo by animal models. The expression of miR-152-3p was quantified by qRT-PCR and its prognostic significance was evaluated. Results: Hypoxic environment promoted the secretion of small extracellular vesicles, and reduced the apoptosis and DNA damage caused by radiation, accompanied by increased expression of small extracellular vesicles miR-152-3p from hypoxic cervical cancer cells. Furthermore, small extracellular vesicles miR-152-3p promoted Hela xenograft growth and reduced the radiosensitivity vivo. Mechanism studies revealed that KLF15 protein was the downstream target of miR-152-3p in regulating radioresistance. Conclusion: Our findings suggest that small extracellular vesicles miR-152-3p affects the therapeutic effect of radiotherapy and holds potential as a biomarker or therapeutic target for cervical cancer prognosis and improving radiotherapy.

Colorectal cancer (CRC) is a malignant tumor marked by high prevalence and a challenging early detection landscape. While tools such as colonoscopy and serum biomarkers enhance screening efficacy, their invasive nature and inadequate sensitivity and specificity hamper their broad adoption. There is a pressing need for non-invasive, precise biomarkers for early diagnosis. The B9D2 gene, which is essential for ciliary function, has been rarely explored in CRC. This study is the first to investigate the diagnostic potential of B9D2 in CRC, using bioinformatics and machine learning to uncover its novel role in early detection, with implications for clinical translation. Gene expression data from whole blood samples obtained from the GEO database were analyzed to identify differentially expressed genes (DEGs) associated with CRC, using a adjusted p-value threshold of < 0.05 and an absolute logFC > 0.5. The biological functions of these genes were investigated through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), the Human Protein Atlas (HPA), and Gene Set Enrichment Analysis (GSEA). Additionally, three machine learning methods—Random Forest (RF), LASSO regression, and Support Vector Machine Recursive Feature Elimination (SVM-RFE)—were employed for feature selection and to evaluate the robustness and predictive power of the selected features, with diagnostic efficacy evaluated through Receiver Operating Characteristic (ROC) curves. Through this analysis, we identified five key genes—B9D2, CR2, DNMT3B, FOS, and PTGS2—from the GSE203024 dataset. Four of these genes have been previously linked to CRC, typically in tissue samples. Our study strengthens their significance as biomarkers by showing their expression in peripheral blood, a non-invasive source, and using multiple analytical methods. Notably, no previous studies have connected B9D2 to CRC, making this discovery a novel contribution. B9D2 expression was significantly upregulated in CRC patients, with an AUC of 0.797 in ROC analysis. This finding was further validated in the GSE47756 dataset, with an AUC of 0.756, confirming its potential as a reliable diagnostic biomarker for CRC. Further IHC staining showed significant different expression of B9D2 between normal and CRC tissue. This study highlights the diagnostic potential of the B9D2 gene in CRC, marking the first time it has been proposed as a biomarker for early detection in CRC. This provides a foundation for its potential application in non-invasive diagnostic methods, such as liquid biopsy. Further experimental and clinical studies are needed to validate B9D2 as a reliable biomarker for early CRC detection and screening. The online version contains supplementary material available at 10.1007/s12672-025-03415-0.