Background and Aims: Liver HCC is the second leading cause of cancer-related deaths worldwide. The heterogeneity of this malignancy is driven by a wide range of genetic alterations, leading to a lack of effective therapeutic options. In this study, we conducted a systematic multi-omics characterization of HCC to uncover its metabolic reprogramming signature. Approach and Results: Through a comprehensive analysis incorporating transcriptomic, metabolomic, and lipidomic investigations, we identified significant changes in metabolic pathways related to glucose flux, lipid oxidation and degradation, and de novo lipogenesis in HCC. The lipidomic analysis revealed abnormal alterations in glycerol-lipids, phosphatidylcholine, and sphingolipid derivatives. Machine-learning techniques identified a panel of genes associated with lipid metabolism as common biomarkers for HCC across different etiologies. Our findings suggest that targeting phosphatidylcholine with saturated fatty acids and long-chain sphingolipid biosynthesis pathways, particularly by inhibiting lysophosphatidylcholine acyltransferase 1 (LPCAT1) and ceramide synthase 5 (CERS5) as potential therapeutic strategies for HCC in vivo and in vitro. Notably, our data revealed an oncogenic role of CERS5 in promoting tumor progression through lipophagy. Conclusions: In conclusion, our study elucidates the metabolic reprogramming nature of lipid metabolism in HCC, identifies prognostic markers and therapeutic targets, and highlights potential metabolism-related targets for therapeutic intervention in HCC.

Prostate cancer (PCa) is an extremely common malignant tumor of the male genitourinary system, originating from the prostate gland epithelium. Male patients are prone to relapse after treatment, which seriously threatens their health. Phosphoinositide 3‐kinase (PI3K)/protein kinase B (PKB, also known as Akt) plays an important role in the growth, invasion, and metastasis of PCa. This review aimed to present an overview of the mechanism of action of the PI3K/AKT signaling pathway in PCa and discuss the application prospects of inhibitors of this pathway in treating PCa, providing a theoretical basis and reference for its clinical treatment targets.

G-rich sequences in DNA and RNA tend to fold into stable secondary structures called G-quadruplexes. Except for the telomere region, G-quadruplex-forming sequences are widely present in gene promoters and have been implicated in transcriptional regulation. Single nucleotide polymorphisms (SNPs) can disrupt the G-quadruplex structure of a gene promoter. In this study, we confirmed the promoter of HSPB2, a cancer-related gene, tends to form an unusual DNA secondary structure. The dual luciferase assay revealed that the SNP rs2234704 in the HSPB2 promoter with a single G > A mutation increased the transcriptional activity of the HSPB2 promoter. Circular dichroism and native PAGE revealed that the G-rich strand of the DNA in this promoter preferred to form a parallel G-quadruplex, which could be destabilized by the SNP rs2234704 (G > A) mutation. Furthermore, we found that the SNP rs2234704 (G > A) greatly increased and influenced the overexpression of HSPB2 in breast cancer samples. These results suggest SNP rs2234704 (G > A) may play a role in the occurrence of breast cancer by destroying the G-quadruplex structure and promoting the expression of HSPB2.

Tumor cells undergo metabolic reprogramming to enable proliferation, survival, and metastasis, making tumor metabolism a key target in cancer research. This study examines current breakthroughs in metabolic reprogramming, including the metabolism of glucose, glutamine, fatty acids, and other nutrients. It describes how these metabolic changes affect anti-tumor immunity and the tumor microenvironment. The molecular processes of metabolic control are investigated. Furthermore, the review discusses practical applications resulting from this study, such as metabolism-based therapy techniques and diagnostic tools. Finally, it discusses future research objectives and difficulties, emphasizing the possibility of targeting tumor metabolism to improve precision cancer therapy.

Endometrial cancer (EC) is a common malignant tumor in women, originating from the endometrial epithelium. Molecular classification of EC aids in guiding treatment, assessing prognosis, and screening for Lynch syndrome. Detection of mismatch repair (MMR) deficiency and microsatellite instability (MSI) status is crucial for guiding immunotherapy and Lynch syndrome screening. This study presents a case of poorly differentiated endometrioid carcinoma, which exhibited MMR deficiency but was microsatellite stable (MSS). Despite the MSS status, the tumor showed signs of genomic instability. Further MLH1 methylation testing suggested that MLH1 promoter methylation may have partially suppressed its expression. These results indicate that the immunohistochemistry (IHC) analysis yielded a negative result, whereas the MSI testing suggested that, although methylation of the MLH1 promoter allows MLH1 expression to largely maintain general genomic stability, it still exhibits signs of underlying instability. In conclusion, for endometrial cancer patients exhibiting dMMR by IHC but MSS by MSI testing, MLH1 promoter methylation testing becomes even more critical. This not only aids in screening for Lynch syndrome, enabling pathologists to make a more precise diagnosis, but also provides important guidance for clinical treatment decisions.