SMAD4 deletion

One novel SMAD4 deleterious mutation (c.1268G > T) was reported. In conclusion, we provide clinicopathological information and new genetic variation data pertinent to CRC in Uganda.

HCC patients with high Smad4 expression exhibited decreased CD8+ T cell infiltration and altered glycolysis. Our results demonstrate that Smad4 in hepatocytes promotes hepatocarcinogenesis and is a potential and candidate target for the prevention and therapy of HCC.

BMP4 expression is required for suppression of metastasis regardless of the SMAD4 status of the tumor cells. Since BMP4 is a secreted protein, we conclude that it can act both in an autocrine manner in SMAD4-expressing tumor cells and in a paracrine manner on stromal cells to suppress metastasis. Deletion of SMAD4 from tumor cells does not prevent BMP4 from suppressing metastasis via a paracrine mechanism.

The presence of a PRKACA/B fusion appears to contribute to oncocytic morphology, but 71% of fusion-positive cases had mixed epithelial subtypes. Rare cases harbored concurrent fusion and driver mutation associated with IPMN. Though fusion-positive lesions were more commonly seen in the non-recurrence group, they also comprised >50% of cases with disease recurrence.

Our results demonstrated that SETD2 inhibits the RAS/ERK signaling pathway by facilitating the transcription of DUSP7 in SMAD4-deficient CRC, which could provide a potential therapeutic target for the treatment of advanced CRC.

This was achieved by conducting a whole-genome CRISPR screens in different colorectal and pancreatic cell lines. A future RAB10 inhibitors could correspond to a new therapeutic solution for patients with cancer with SMAD4 deletion.

CSF ctDNA could more sensitively detect molecular markers and metastasis-related mechanisms than tumor tissues in GCLM patients, and our study sheds light on utilizing CSF ctDNA in prognostic estimation and clinical assessment in GCLM.

Overall survival outcome analysis with combinations of GDF15, IL17, FOXP3 and CXCL1 did not improve overall odds ratios (HR=3.51, p=5.9E 6 ) but did increase the overall significance of the correlation with EAC patient survival. Conclusion : We demonstrate that the poor survival associated with SMAD4 dysfunction in EAC cases is associated with promotion of metastatic and immuno-suppressive phenotypes through GDF15 levels.

Conclusions SMAD4 deleterious mutations are highly diverse and present at low to moderate frequencies across many cancers. SMAD4 mutations may represent a more sensitive biomarker to identify patients at greater risk for developing metastatic disease and are likely involved in the transformation from localized to metastatic disease.

Furthermore, retarded tumor growth of Smad4-deficient PDAC cells on B6 mice is largely reversed when Sting is codeleted, or when the cells are implanted into interferon-alpha receptor-deficientmice or cDC1-deficientmice. Accordingly, Smad4 deficiency promotes PDAC immunogenicity by inducing tumor-intrinsic DNA damage-elicited type I interferon signaling.

Meanwhile, the low-risk group was significantly enriched in metabolism-related pathways and suggested the potential to target tumor metabolism to develop specific drugs. Overall, SDIS could robustly predict prognosis in PACA, which might serve as an attractive platform to further tailor decision-making in chemotherapy and immunotherapy in clinical settings.

We provide molecular signatures associated with different levels of TGF-β to deepen the understanding of the role of TGF-β in GIAD and provide potential drug possibilities for therapeutic targets in different levels of TGF-β in GIAD.

In conclusion, our study suggests a new mechanism for the action of benzoate metabolites derived from plant-based foods. This mechanism could be exploited clinically to upregulate Smad4 in colonic epithelium and NK cells, thereby delaying CRC progression.

Taken together, our study revealed that macrophages contribute to SCC expansion through interactions with tumor cells but are dispensable for SCC metastasis. Our study provides novel insights into understanding the contributions and limitations of TAMs in SCC progression.