Non-small cell lung cancer (NSCLC), a leading cause of cancer-related deaths worldwide, remains a significant clinical challenge despite advances in immune checkpoint inhibitors therapy, with drug resistance persisting as a major obstacle. Palmitoylation, a critical post-translational modification (PTM) primarily catalyzed by palmitoyltransferases of the zinc finger DHHC-type (ZDHHC), has recently demonstrated important implications in NSCLC. This review aims to elucidate the mechanisms and clinical potential of ZDHHC-mediated protein palmitoylation in NSCLC progression and immune escape.
.
Humans ; Lipoylation ; Lung Neoplasms/pathology* ; Acyltransferases/genetics* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Animals

Objective To explore the expression level of zinc finger CCCH-type containing 13 (ZC3H13)in gastric cancer based on bioinformatics techniques,along with clinicopathological stag-ing,prognostic survival,immune infiltration,correlation analysis,protein-protein interactions,and enrichment analysis.Methods Using the UALCAN database and the Gene Expression Profiling Inter-active Analysis(GEPIA)databases,the expression differences of ZC3H13 between normal gastric tis-sues and gastric cancer tissues,as well as the significance of clinical pathological data were compared.The correlation between ZC3H13 expression levels in gastric cancer tissues and patient survival progno-sis was assessed using univariate survival analysis through the Kaplan-Meier Plotter website and the GEPIA database.The relationship between ZC3H13 expression and immune infiltration levels in gastric cancer was explored using the Tumor Immune Estimation Resource(TIMER)database.Co-expression genes significantly correlated with ZC3H13 expression in gastric cancer were identified through the Linkedomics database.The protein-protein interaction network of ZC3H13 and its common target genes in gastric cancer was constructed using the STRING website,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.Results Compared to normal gastric tissues,ZC3H13 was significantly upregulated in gastric cancer,and its high ex-pression was closely associated with patient age,ethnicity,tissue subtype,and other factors.Pa-tients with high ZC3H13 expression showed no statistically significant difference in overall survival(OS)or progression-free survival(PFS)time compared to patients with low expression(P＞0.05).Immune analysis revealed a significant negative correlation between ZC3H13 expression and the infiltration density of CD8+T cells,macrophages,neutrophils,and dendritic immune cells in gastric cancer(P＜0.05).Correlation analysis showed that ZC3H13 expression in gastric cancer was significantly positively correlated with the gene expression of DAK,DDK1,and BCL7C,and negatively correlated with the expression of FAM10A4,SLC6A7,and TAC1(P＜0.05).The pro-tein interaction network indicated that proteins interacting with ZC3H13 in gastric cancer included VIRMA,WTAP,METTL3,METTL14,RBM15,and others.Enrichment analysis revealed that dif-ferentially expressed genes in gastric cancer were mainly enriched in RNA polymerase,nucleotide excision repair,thyroid hormone signaling pathway,and other pathways.Conclusion ZC3H13 is overexpressed in gastric cancer,and its elevated expression is linked to the clinicopathological stage,patient survival time,and immune cell infiltration levels.Additionally,ZC3H13 may partici-pate in the initiation and progression of gastric cancer through interactions with key molecules such as VIRMA and METTL3.These findings suggest that ZC3H13 could serve as a potential biomarker and therapeutic target for gastric cancer prognosis.

Objective:To discuss the associations of mismatch repair(MMR)in gastric cancer with preoperative inflammatory indicators and clinicopathological features in the gastric cancer patients,and to construct a gastric cancer MMR predictive model based on preoperative inflammatory indicators and clinicopathological features of the gastric cancer patients,and to provide new ideas for evaluation of MMR status in gastric cancer.Methods:The data of 254 gastric cancer patients who underwent surgical treatment from September 2020 to October 2023 were included.According to the expression of MMR protein,the patients were divided into MMR normal(proficiout MMR,pMMR)group and MMR deficient(dMMR)group.The preoperative inflammatory indicators and clinicopathological features data of the gastric cancer patients in two groups were collected.The associations between inflammatory indicators,clinicopathological features,and MMR in dMMR group and pMMR group were analyzed using Chi-square test.The independent predictive factors for dMMR were selected to construct the nomogram.Receiver operating characteristic(ROC)curve and calibration curve were used to evaluate the predictive efficacy,and decision curve was used to evaluate the practicality of the predication model.Results:A total of 254 gastric cancer patients were included in the study,with 221 patients(87％)in pMMR group and 33 patients(13％)in dMMR group.There were statistically significant differences(P＜0.05)in age,tumor location,tumor differentiation degree,maximum tumor diameter,platelet-to-lymphocyte ratio(PLR),alkaline phosphatase(AKP),alkaline phosphatase-to-albumin ratio(AAR),fibrinogen(FB)-to-lymphocyte(FLR),FB-to-albumin(AL)(FAR),D-dimer(D-D),and FB of the gastric cancer patients between dMMR group and pMMR group.Univariate and multivariate Logistic regression analysis revealed maximum tumor diameter[odd ratio(OR)=2.958,95％confidence interval(CI):1.196-7.314,P=0.019],tumor location(OR=4.013,95％CI:1.596-10.089,P=0.003),tumor differentiation(OR=3.006,95％CI:1.250-7.230,P=0.014),FAR(OR=2.793,95％CI:1.179-6.616,P=0.020),and carbohydrate antigen 199(CA199)(OR=0.279,95％CI:0.084-0.929,P-0.038)were the independent predictors of dMMR.The area under the ROC curve(AUC)value of the gastric cancer MMR prediction model constructed based on inflammatory indicators and clinical pathological characteristics was 0.800 with the sensitivity of 0.851 and the specificity of 0.606.The calibration curve of the nomogram was found to fit the ideal curve well,and in Hosmer-Lemeshow test P=0.412,the clinical decision curve showed a better net benefit.Conclusion:The preoperative inflammatory indicators and clinicopathological features are associated with MMR in gastric cancer;maximum tumor diameter,tumor location,tumor differentiation,CA199,and FAR are the independent predictors of dMMR.The prediction model based on the above predictors could predict the MMR status of the dMMR gastric cancer patients.

Drug delivery system (DDS) holds promise in reducing off-target effects of antitumor drugs. The carriers of antitumor drug DDS mainly include nanoparticles, small molecules, nucleic acids, peptides, antibodies and cells, which carry antitumor drugs through linker to deliver the drugs to specific tumor tissues and cells. DDS will propel progress in the field of cancer precision medicine.

Tumor-related death is often associated with tumor metastasis. Metastasis process includes the acquisition of dissemination traits of tumor cells, dormancy awakening, and distant growth. Changing dissemination traits of cancer cells, maintaining and killing dormant tumor cells, editing pre-metastatic microenvironment, and reprogramming hallmarks of cancer will be key to block tumor metastasis. Bevacizumab, denosumab and cilengitide have been approved for clinical therapies. Tumor screening based on blood tests combined with artificial intelligence will provide new targeted metastasis strategies for clinical treatment.

Optical tweezers are a means to manipulate objects with light. Optical tweezers can obtain a nanometer space, piconewton force, and a millisecond resolution; thus, they are excellently suited for studying biological processes from the single-cell to the single-molecule level. Optical tweezers can screen and manipulate tumor cells, study single molecule, and monitor cancer treatments. Thus, optical tweezers will promote the progress of cancer research and treatments.

Cancer phenotypic plasticity includes dedifferentiation, blocked differentiation and trans- differentiation, and differentiation therapy targeting tumor cell plasticity is becoming a new therapeutic model for human cancers. The application of inducing differentiation, initiating differentiation and regulating differentiation in tumor differentiation therapy will promote the directed differentiation of tumor cells into mature cells and the remodeling of phenotypes, thus to achieve the purpose of cancer treatment.

Cytotoxic agents, molecular targeted agents and immune checkpoint inhibitors consist of the fundamental model of cancer systematic treatments. Anti-tumor drugs with new mechanisms of action, including kinase inhibitors, therapeutic antibodies, nucleic acid blocks, therapeutic vaccines, gene-edited immune cells, living microrobots and digital drugs, will change this existing model. Drugs targrting nerves, polysaccharides, lipids and microflora may gradually enter clinical applications.

As one of the typical bioorthogonal chemistry reactions, click chemistry joins molecules similar to “Lego”. Bioorthogonal click chemistry is used to modify cancer cells, design antitumor drugs, delivery drugs, manipulate immune cells, and help preclinical evaluation. Click chemistry provides a promising approach for discovering molecules and targeting cancer in cancer research.

Autophagy is a cellular self-degradation process essential for maintaining metabolic functions in cells and organisms.Dysfunc-tional autophagy has been linked to various diseases,including cancer.The m6A modification,a major RNA modification in eukaryotes,plays a crucial role in regulating autophagy in tumor cells by regulating the expression of autophagy-associated genes(ATGs)or interfering with autophagy-related signaling pathways.Aberrant m6A modification can lead to dysregulated autophagy and impact tumor progression.However,the specific role of m6A in regulating tumor autophagy remains to be explored.Therefore,in this review,we discuss the role of m6A modification in tumor cell autophagy and examine its relationship with tumor progression and drug resistance,aiming to provide a the-oretical foundation for developing new therapeutic strategies.