Emerging mounts of research support the ancestral theory of cancer, indicating that tumorigenesis and embryogenesis share many similar biological features, yet yield distinct outcomes. Gene co‐expression networks underlie both embryonic development and tumorigenesis. We hypothesize that deviations in the gene interaction patterns in tumors compared to villi predispose to malignancy and worse prognosis.

By constructing a gene co‐expression network of villi and colorectal cancer (CRC) and conducting functional enrichment analysis to identify “off‐track genes.” Cox regression assessed prognostic significance, while tissue microarrays evaluated protein expression and progression. Additionally, mRNA sequencing of chondroitin polymerizing factor (CHPF)‐knockdown LOVO and SW480 cell lines was conducted and validated via in vitro assays.

We found that genes in villi and CRC have similar functions, but the genes that performed corresponding functions were not identical. Then, according to “off‐track theory” and linear regression models, we obtained 24 genes whose aberrant expression was significantly associated with poor CRC survival. Notably, CHPF emerged as an adverse prognostic factor. Immunohistochemical analysis confirmed that CHPF is an independent prognostic marker for CRC. Furthermore, cell phenotype assays demonstrated that CHPF enhances proliferation and migration, suppresses apoptosis, and engages in the TNF signaling pathway.

These findings validate that villi development can serve as a research model for tumorigenesis, and identify CHPF is an independent oncogenic factor in CRC, suggesting its potential as a prognostic biomarker and a therapeutic target for clinical treatment.

Glioma is the most common malignant tumor in the central nervous system, with unclear pathogenesis and poor treatment outcomes. Recent research reveals that the brain–gut axis—involving gut microbiota and immune activity—influences central nervous system tumors. Given the pivotal role of the brain–gut axis in glioma, our study aimed to elucidate the causal association between gut microbiota and glioma, and to identify potential immune‐mediated effects and therapeutic targets.

Based on publicly available genome‐wide association study data, our research employed multi‐subgroup, replicated, Bayesian weighted, and summary statistics‐based two‐sample Mendelian randomization (MR) studies, combined with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) systematic review strategy, to systematically evaluate the potential causal effects of gut microbiota on glioma and their immune‐mediated traits.

The initial screening identified 53 gut microbiota and 58 plasma immune traits with potential causal associations with glioma. Through external data and systematic review from six studies, we ultimately confirmed five gut microbiota‐plasma immune trait‐glioma pathways. CD28⁺CD45RA⁻ CD8dim Treg (OR = 0.019, p = 0.007) mediated the risk of Bacteroides A plebeius A (OR = 0.149, p = 0.036) on glioma, accounting for 2.99% of the effect; the proportion of CD4⁺ memory T cells in whole blood (OR = 0.066, p = 0.029) mediated the risk of Bacteroides sp002160055 (OR = 0.158, p = 0.024) on non‐glioblastoma(GBM), accounting for 8.51% of the effect, while the risk of Faecalicoccus (OR = 0.345, p = 0.005) on non‐GBM was jointly mediated by the absolute number of Naive CD8br and the expression of CD19 in IgD⁺ CD38br B cells. The protective effect of Faecalibacterium sp002160895 on GBM was mediated by 7.59% of the expression level of CD4 in Treg cells.

Our study, through MR analysis, revealed the causal relationship between gut microbiota and the susceptibility to glioma, and for the first time proposed the important role of circulating immune cells in this process, providing new potential biomarkers for the early diagnosis and treatment of glioma.

This study was aimed at analyzing the efficacy and safety of an injectable form of chlorogenic acid (CGA) in patients with recurrent high-grade glioma after standard of care treatments, through a first-in-human, open-label, dose-escalation phase Ⅰ trial.

A total of 26 eligible patients were enrolled, received intramuscular CGA injections at 5 dose levels, and were followed up for 5 years. CGA was well tolerated, and the maximum tolerated dose was 5.5 mg/kg.

The most common treatment-related adverse events occurred at the sites of injection. No grade 3 or 4 adverse events (e.g., drug allergy) were reported for these patients except for induration at the injection sites. A clinical pharmacokinetic study showed that CGA was rapidly eliminated from the plasma, with a t_1/2 of 0.95-1.27 h on day 1 and 1.19-1.39 h on day 30, and no detectable CGA was observed on days 9, 11, 13, 23, 25, 27, and 29 before CGA administration. After the first treatment cycle, 52.2% of patients (12 of 23) achieved stable disease. Long-term follow-up indicated an estimated median overall survival of 11.3 months for all 23 evaluable patients. Of the 18 patients with grade 3 glioma, the median overall survival was 9.5 months. Two patients remained alive at the cutoff day.

This phase Ⅰ study demonstrated that CGA has a favorable safety profile (with no severe toxicity), and provides preliminary clinical benefits for patients with high grade glioma relapsing after prior standard therapies, thus shedding light on the potential clinical application of CGA for recurrent grade 4 glioma.