Betulinic acid (BA) is a pentacyclic triterpene compound that can be obtained by separation, chemical synthesis and biotransformation from birch. BA has antitumour activity, and its mechanisms of action mainly include the induction of mitochondrial oxidative stress; the regulation of specificity protein transcription factors, and the inhibition of signal transducer and activator of transcription 3 and nuclear factor-κB signalling pathways. In addition, BA can increase the sensitivity of cancer cells to other chemotherapy drugs. Recent studies have shown that BA plays an anticancer role in several kinds of tumour diseases. In this article, the anticancer mechanism of BA and its application in the treatment of tumour diseases are reviewed.

As a typical pathological feature of pancreatic ductal adenocarcinoma, reprogramming of glucose metabolism synergistically drives the tumorigenesis and development process through molecular mechanisms such as regulating the expression of driver genes, modifying key functional proteins, triggering mitochondrial metabolism abnormality, and remodeling the tumor microenvironment. It is worth noting that this metabolic remodeling phenomenon is significantly associated with the formation of chemoresistance. Based on the latest research progress, this paper systematically describes the molecular basis of glucose metabolic reprogramming in pancreatic cancer, drug resistance characteristics and its targeted intervention strategies, and provides a theoretical framework for the research and development of innovative drugs.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by marked molecular and epithelial heterogeneity, but the cross-cohort and cellular context of candidate genes remains incompletely resolved. We integrated bulk transcriptomic and proteomic data with patient-grouped machine-learning assessment, independent-cohort expression replication, cross-cohort functional modelling, single-cell RNA sequencing, spatial transcriptomics, CNV-assisted analysis and cell-line qRT-PCR. Transcriptomic and proteomic screening identified 4,701 differentially expressed genes, 531 differentially expressed proteins and 238 genes with concordant directions. Four-algorithm integration prioritized a 21-gene candidate space. Repeated patient-grouped cross-validation yielded mean outer-fold AUCs of 0.990 for XGBoost and 0.993 for random forest. These values represent exploratory internal stability within a prespecified candidate space, rather than unbiased external predictive performance, because feature selection preceded the resampling procedure. In GSE62452, HK2, S100A2 and GALNT5 showed single-gene AUCs of 0.845, 0.745 and 0.891, respectively, while an equal-weight, within-cohort Z-score produced an AUC of 0.895 but did not outperform GALNT5. Across five RNA cohorts, HK2 was associated with glycolysis and hypoxia, S100A2 with a PDAC basal-like/squamous-aligned program, and GALNT5 with mucin O-glycosylation and O-glycan biosynthesis. Single-cell and spatial analyses supported heterogeneous epithelial localization and descriptive CNV-anchored concordance. CopyKAT classified 1,587 of 3,244 epithelial candidate cells as aneuploid, while 1,009 cells remained undefined. qRT-PCR showed higher relative HK2, S100A2 and GALNT5 mRNA levels in PDAC cell lines than in HPNE cells. These findings associate the three genes with complementary epithelial/ductal-like programs in PDAC, but do not establish causal regulation, tumor specificity, independent prognostic value or direct therapeutic targetability.