Background: The prognosis for esophageal squamous cell carcinoma (ESCC) patients with lymph node metastasis (LNM) is still dismal. Elucidation of the LNM associated genomic alteration and underlying molecular mechanisms may provide clinical therapeutic strategies for ESCC treatment. Methods: Joint analysis of ESCC sequencing data were conducted to comprehensively survey SCNAs and identify driver genes which significantly associated with LNM. The roles of miR-548k in lymphangiogensis and lymphatic metastasis were validated both in vitro and in vivo. ESCC tissue and blood samples were analyzed for association between miR-548k expression and patient clinicopathological features and prognosis and diagnosis. Results: In the pooled cohort of 314 ESCC patients, we found 76 significant focused regions including 43 amplifications and 33 deletions. Clinical implication analysis revealed a panel of genes associated with LNM with the most frequently amplified gene being MIR548K harbored in the 11q13.3 amplicon. Overexpression of miR-548k remarkably promotes lymphangiogenesis and lymphatic metastasis in vitro and in vivo. Furthermore, we demonstrated that miR-548k modulating the tumor microenvironment by promoting VEGFC secretion and stimulating lymphangiogenesis through ADAMTS1/VEGFC/VEGFR3 pathways, while promoting metastasis by regulating KLF10/EGFR axis. Importantly, we found that serum miR-548k and VEGFC of early stage ESCC patients were significantly higher than that in healthy donators, suggesting a promising application of miR-548k and VEGFC as biomarkers in early diagnosis of ESCC. Conclusions: Our study comprehensively characterized SCNAs in ESCC and highlighted the crucial role of miR-548k in promoting lymphatic metastasis, which might be employed as a new diagnostic and prognostic marker for ESCC.

The role of cyclin B1 in the clinical therapeutic sensitivity of human esophageal squamous cell carcinoma (ESCC) remains to be defined. In this study, we found that elevated cyclin B1 expression attenuated the apoptosis induced by cisplatin or paclitaxel, while knockdown of cyclin B1 enhanced cisplatin or paclitaxel sensitivity in ESCC cells. Cyclin B1-mediated apoptosis may rely on the Bcl-2-dependent mitochondria-regulated intrinsic death pathway, and the antagonizing effect of cyclin B1 on chemotherapeutic agent-induced apoptosis was through PTEN/Akt pathway. Therefore, cyclin B1 might be a therapeutic target for the development of specific and efficient approaches in the treatment of ESCC.

Numerous techniques excel in brain tumor segmentation using multi-modal magnetic resonance imaging (MRI) sequences, delivering exceptional results. However, the prevalent absence of modalities in clinical scenarios hampers performance. Current approaches frequently resort to zero maps as substitutes for missing modalities, inadvertently introducing feature bias and redundant computations. To address these issues, we present the Token Merging transFormer (TMFormer) for robust brain tumor segmentation with missing modalities. TMFormer tackles these challenges by extracting and merging accessible modalities into more compact token sequences. The architecture comprises two core components: the Uni-modal Token Merging Block (UMB) and the Multi-modal Token Merging Block (MMB). The UMB enhances individual modality representation by adaptively consolidating spatially redundant tokens within and outside tumor-related regions, thereby refining token sequences for augmented representational capacity. Meanwhile, the MMB mitigates multi-modal feature fusion bias, exclusively leveraging tokens from present modalities and merging them into a unified multi-modal representation to accommodate varying modality combinations. Extensive experimental results on the BraTS 2018 and 2020 datasets demonstrate the superiority and efficacy of TMFormer compared to state-of-the-art methods when dealing with missing modalities.

TP53 gene mutations occur in more than 50% of human cancers and the vast majority of these mutations in human cancers are missense mutations, which broadly occur in DNA binding domain (DBD) (Amino acids 102–292) and mainly reside in six “hotspot” residues. TP53 G245C and R273H point mutations are two of the most frequent mutations in tumors and have been verified in several different cancers. In the previous study of the whole genome sequencing (WGS), we found some mutations of TP53 DBD in esophageal squamous cell carcinoma (ESCC) clinical samples. We focused on two high-frequent mutations TP53 p.G245C and TP53 p.R273H and investigated their oncogenic roles in ESCC cell lines, p53-defective cell lines H1299 and HCT116 p53−/−. MTS and colony formation assays showed that mutant TP53 G245C and R273H increased cell vitality and proliferation. Flow cytometry results revealed inhibition of ultraviolet radiation (UV)- and ionizing radiation (IR)- induced apoptosis and disruption of TP53-mediated cell cycle arrest after UV, IR and Nocodazole treatment. Transwell assays indicated that mutant TP53 G245C and R273H enhanced cell migration and invasion abilities. Moreover, western blot revealed that they were able to suppress the expression of TP53 downstream genes in the process of apoptosis and cell cycle arrest induced by UV, which suggests that these two mutations can influence apoptosis and growth arrest might be due, at least in part, to down-regulate the expression of P21, GADD45α and PARP. These results indicate that mutant TP53 G245C and R273H can lead to more aggressive phenotypes and enhance cancer cell malignancy, which further uncover TP53 function in carcinogenesis and might be useful in clinical diagnosis and therapy of TP53 mutant cancers.

Background: Chronic subdural hematoma (CSDH) is a common neurosurgical condition that predominantly affects elderly individuals and is characterized by the accumulation of blood between the dura mater and the brain surface. Temporal muscle thickness (TMT) has emerged as a potential prognostic marker for various neurological diseases, including CSDH. This study aimed to evaluate the prognostic value of TMT in patients with CSDH. Methods: This retrospective study assessed TMT in patients with CSDH using cranial CT scans. We examined the correlation between TMT and CSDH-related clinical characteristics and evaluated the prognostic relevance of TMT. Results: A total of 844 participants were included in the study. TMT was significantly lower in patients with CSDH than in the control group ( p < 0.001). The difference in TMT was strongly associated with the side of CSDH occurrence ( p < 0.001), with CSDH more likely to develop on the side with lower TMT (OR = 0.219, 95% CI: 0.179–0.269). Lower average TMT was significantly associated with a higher likelihood of poor functional outcomes (OR = 0.560, 95% CI: 0.391–0.804, p = 0.002). Additionally, our analysis showed significant associations between TMT and age ( p < 0.001), alcohol consumption ( p = 0.009), cardiac disease ( p = 0.006), brain infarction ( p < 0.001), headache ( p < 0.001), limb weakness ( p < 0.001), and postoperative disturbance of consciousness ( p = 0.029). Conclusion: The occurrence of CSDH is significantly correlated with the side of lower TMT. TMT may serve as an important prognostic marker in patients with CSDH, particularly for predicting functional outcomes.