Army Medical Center

This study elucidated the regulatory role of the TFEB-HNRNPA2B1 feedback loop in hepatocellular carcinoma (HCC) metastasis, a highly prevalent and aggressive liver cancer subtype. The findings demonstrated that transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, was significantly upregulated in HCC tissues, particularly in advanced-stage tumors and lymph node metastatic lesions. Functional studies revealed that TFEB overexpression enhanced metastatic potential in HCC cell lines, whereas its genetic knockdown substantially suppressed metastatic capacity. Mechanistic investigations identified HNRNPA2B1 as a critical mRNA stabilizer of TFEB, establishing a reciprocally reinforcing feedback loop wherein TFEB transactivated HNRNPA2B1 expression. This autoregulatory circuit drove metastatic progression through coordinated upregulation of pro-metastatic genes, ultimately promoting HCC cell dissemination. These results suggested therapeutic targeting of the TFEB-HNRNPA2B1 axis as a promising strategy for inhibiting liver cancer metastasis.

TP53 mutation is a critical predictor of early disease progression and poor prognosis in mantle cell lymphoma (MCL). Optimal treatment for these patients remains unclear. This systematic review and meta-analysis evaluated various strategies for achieving remission in TP53-mutated (TP53m) MCL.

We searched EMBASE, MEDLINE and conference proceedings from inception to May 7, 2025, without language restrictions. Randomised controlled trials, single-arm trials, and prospective or retrospective observational studies assessing remission strategies in newly diagnosed or relapsed/refractory TP53m MCL were included. Case reports, case series, and non-human studies were excluded. Two authors independently selected studies, extracted summary data from published reports, and assessed bias risk. Outcomes of interest were complete remission (CR) rate, overall response rate (ORR), overall survival (OS), and progression-free survival (PFS). Random-effects meta-analyses were used for summary estimation. The study is registered with PROSPERO, CRD42024594152.

A total of 9833 studies were identified, of which 39 studies involving 734 patients with TP53m MCL were eligible. For newly diagnosed TP53m MCL, targeted therapy (TT) had a CR rate of 89% (95% confidence interval (CI) 80-99; n = 52; I² = 0%), an ORR of 96% (95% CI 89-100; n = 48; I² = 0%), a median OS of 38.5 months (95% CI 37.74-39.26; n = 6), a 2-year OS rate of 76% (19/25) (95% CI 55-91; n = 25), a median PFS of 38.5 months (95% CI 37.74-39.26; n = 6) and a 2-year PFS rate of 62% (95% CI 33-87; n = 30; I² = 44%). For relapsed/refractory TP53m MCL, allogeneic hematopoietic stem cell transplantation (Allo-HSCT) had a CR rate of 100% (95% CI 65-100; n = 4; I² = 0%) and an ORR of 100% (95% CI 65-100; n = 4; I² = 0%); Chimeric antigen receptor-T (CAR-T) cell therapy had a CR rate of 85% (95% CI 69-100; n = 75; I² = 66%), an ORR of 90% (95% CI 83-98; n = 67; I² = 0%), a 2-year OS rate of 44% (37/61) (95% CI 32-58; n = 61), and 2-year PFS rates of 31% (19/61) (95% CI 20-44; n = 61); TT had a CR rate of 53% (95% CI 39-73; n = 95; I² = 60%), an ORR of 64% (95% CI 53-77; n = 139; I² = 50%), a median OS of 10.87 months (95% CI 6.41-15.33; n = 57; I² = 0%), a 2-year OS rate of 53% (95% CI 45-62; n = 141; I² = 0%), a median PFS of 7.83 months (95% CI -0.89-16.55; n = 31; I² = 80%) and a 2-year PFS rate of 28% (95% CI 14-44; n = 141; I² = 72%).

Our findings indicate that TT may benefit patients with newly diagnosed TP53m MCL, and Allo-HSCT, CAR-T cell therapy, or TT could be considered for relapsed/refractory cases. However, -suboptimal long-term survival highlights the urgent need for innovative therapies. Key limitations, including small sample sizes and few randomised controlled trials (RCTs), emphasize the need for well-designed RCTs with adequate sample size in this field.

The Chongqing Natural Science Foundation and Talent Innovation Capability Cultivation Program of the Army Medical Center.