Dong-Yan Shen

Burkitt lymphoma (BL) with TP53 mutations is characterized by strong chemoresistance and poor prognosis, posing significant challenges in clinical treatment. Chimeric antigen receptor T-cell (CAR-T) therapy has shown promise in refractory/relapsed (r/r) BL, but its efficacy in TP53-mutated cases remains to be further validated. This case report describes a 16-year-old male adolescent diagnosed with TP53-mutated BL, whose initial presentation with recurrent abdominal pain led to a misdiagnosis of high-grade B-cell lymphoma. The disease was refractory to two cycles of chemotherapy (DA-EPOCH-R and AZA + R-CDOP) and even progression after third-line R-CODOX-M therapy. Following reevaluation confirming BL, the patient received CD19-directed CAR-T cell therapy (Axicabtagene Ciloleucel infusion, Axi-cel) and achieved complete metabolic response (CMR). Baseline lactate dehydrogenase (LDH) was markedly elevated at 1,343 U/L. As of the latest follow-up in March 2025, the patient remains in remission at 30 months after CAR-T infusion with full functional recovery, including resumption of normal academic life. This case, among the youngest reported uses of commercial Axi-cel for BL, highlights the diagnostic complexity in adolescent lymphoma and demonstrates that CD19 CAR-T therapy can overcome TP53-associated chemoresistance in adolescent BL. It also suggests that integrating molecular profiling and immunotherapy may provide new strategies for managing high-risk, treatment-refractory cases in the adolescent and young adult population.

GRWD1, a novel WD40-repeat-containing protein designated glutamate-rich WD repeat, is highly expressed in CRC and participates in a series of oncogenic activities. However, the cause of GRWD1 overexpression and its oncogenic mechanism in CRC remains elusive. This study revealed that GRWD1 was correlated with inflammation and was progressively upregulated during the progression of Azoxymethane/Dextran sodium sulfate (AOM/DSS) in a mouse model. Moreover, GRWD1 was activated by the IL-6/STAT3 signal pathway in CRC cells. Besides, it promoted the degradation of p53 and further induced GLUT1 to facilitate aerobic glycolysis in CRC. Taken together, GRWD1 played an oncogenic role in tumorigenesis of CRC and represented a promising therapeutic target.

Colorectal cancer (CRC) ranks as the third most frequently diagnosed cancer and is the second leading cause of cancer-related deaths globally. Recently, RNA-binding protein 39(RBM39), a critical factor in tumor-targeted mRNA and protein expression, has played a vital role in tumorigenesis and has broad development prospects in clinical treatment and drug research. However, the functional roles of RBM39 in the progression of CRC remain largely unexplored. This study found that RBM39 is notably overexpressed at both the mRNA and protein levels in CRC tissues compared with normal adjacent tissues. RBM39 was identified as a potential therapeutic target for colorectal cancer. Elevated RBM39 mRNA levels in CRC patients indicated worse survival probabilities. We show that RBM39 enhances the proliferation, migration, and invasion ability of CRC cells. Furthermore, we have made an innovative discovery that increased RBM39 inhibits apoptosis in CRC cells. Mechanistically, RNA-seq analysis indicated that RBM39 activates the NF-κB pathway, which plays a pivotal role in driving the malignant biological behaviors of colorectal cancer. Notably, these findings represent a novel contribution to our understanding of the mechanistic underpinnings of CRC, as they have not been previously documented in the literature. In the in vivo nude mouse xenograft model, our study demonstrates that the targeted knockdown of RBM39 markedly suppresses tumor formation, highlighting a novel therapeutic strategy for combating colorectal cancer. In conclusion, RBM39 emerges as a promising candidate for clinical diagnosis and targeted treatment of colorectal cancer, with implications for future research in tumor biology and therapeutic strategies.

Background: Human tumors pose significant challenges, with targeted therapy against specific molecular targets or signaling pathways being a mainstay alongside surgical resection. Previous studies have implicated KHDRBS1 in the oncogenesis of certain human tumors such as colorectal and prostate cancers, underscoring its potential as a therapeutic target. However, the comprehensive expression pattern of KHDRBS1 in hepatocellular carcinoma (HCC) warrants further exploration.Methods: Integrating and analyzing multi-omics, multi-cohort data from public databases, coupled with clinical samples and molecular biology validation, we elucidate the oncogenic role of KHDRBS1 in HCC progression. Additionally, leveraging HCC single-cell sequencing data, we segregate malignant cells into KHDRBS1-positive and negative subsets, uncovering significant differences in their expression profiles and functional roles.Results: Our study identifies KHDRBS1 as a tumor-promoting factor in HCC, with its positivity correlating with tumor progression. Furthermore, we highlight the clinical significance of KHDRBS1-positive malignant cells, aiming to further propel its clinical utility.Conclusion: KHDRBS1 plays a key role in HCC development. This study provides crucial insights for further investigation into KHDRBS1 as a therapeutic target in HCC.

Objective: The tumor microenvironment (TME) in cholangiocarcinoma (CHOL) is typically characterized by a low level of immune infiltration, which accounts for the dismal prognosis of this patient population. This study sought to investigate the mechanisms underlying the reduced infiltration of immune cells into the CHOL TME. Methods: We constructed a Least Absolute Shrinkage and Selection Operator (LASSO) regression model to identify prognosis-related differentially expressed genes (DEGs). The 'Corrplot' package was employed to analyze the correlation between dermatopontin (DPT) and immune infiltration in CHOL. The Tumor and Immune System Interaction Database (TISIDB) was used to evaluate the association between DPT and immunology. Single-cell analysis was conducted to localize CCL19 secretions. Western blot and qPCR were utilized to detect DPT expression, while immunofluorescence was performed to investigate the cellular localization of DPT. Additionally, ELISA analysis was employed to assess the alteration in CCL19 secretion in cancer-associated fibroblasts (CAFs) and macrophages. Results: Our findings revealed that CHOL patients with low DPT expression had a poorer prognosis. Enrichment analysis demonstrated a positive correlation between DPT levels and the infiltration of immunomodulators and immune cells. Moreover, high DPT levels were associated with enhanced anti-PD-1/PD-L1 immunotherapeutic responses. Furthermore, DPT expression impacted the landscape of gene mutations, showing a negative association with tumor grade, stage, and lymph node metastasis. Based on the results of protein peptides analysis and cell experiments, it was inferred that the downregulation of DPT in CHOL cells effectively suppressed the secretion of CCL19 in macrophages. Conclusions: DPT is a novel prognosis-related biomarker for CHOL patients, and this study provides preliminary insights into the mechanism by which DPT promotes the infiltration of immune cells into the CHOL TME.