ABSTRACT
BACKGROUND: To investigate the role of achaete-scute complex-like 2 (ASCL2) in stomach adenocarcinoma (STAD), we analyze whether ASCL2 suppression could retard cancer development and further observe the relevance between ASCL2 and inflammation via Toll-like receptor 4 (TLR4) activation in STAD, both in vitro and in vivo. METHODS: Proliferation, development, inflammation, and apoptosis in STAD are observed using sh-ASCL2 lentivirus via TLR4 activation in vitro and in vivo. The relationship between ASCL2 and inflammation is analyzed. Western blotting of ASCL2 with the target protein of immune-associated cells is performed. The prognosis of STAD and associated ASCL2 mutation are analyzed. RESULTS: The ASCL2 level in STAD tumor tissues is increased, compared to normal tissues, and brings a worse prognosis. The ASCL2 shows a negative correlation with inflammation, and TLR4 reveals a positive correlation with gastric cancer. ASCL2 expression is high in MGC803 cells. Sh-ASCL2 could reduce STAD development by decreasing proliferation, tumor volume, and biomarker levels and increasing apoptosis in vitro and in vivo. The inflammatory role of ASCL2 is regulated through TLR4 activation. ASCL2 levels may be related to CNTNAP3, CLIP1, C9orf84, ARIH2, and IL1R2 mutations; positively correlated with M2 macrophage and T follicular helper cell levels; negatively correlated with neutrophil, dendritic cell, monocyte, CD8 T cell, and M1 macrophage levels; and involved in STAD prognosis. CONCLUSIONS: The ASCL2 may adjust inflammation in STAD through TLR4 activation and may be associated with related immune cells. ASCL2 is possibly an upstream target factor of the TLR4 signaling pathway.
Subject(s)
Adenocarcinoma , Stomach Neoplasms , Adenocarcinoma/genetics , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Humans , Inflammation , Stomach Neoplasms/genetics , Toll-Like Receptor 4/genetics , Ubiquitin-Protein LigasesABSTRACT
BACKGROUND: Liver metastasis is the primary cause of lethal colorectal cancer (CRC). The predominant risk of poor patient prognosis in early-stage CRC emerges as metachronous liver metastasis. This necessitates the search for potential biomarkers for this metastasis to assess treatment outcomes and provide targeted therapy. METHODS: The role of hsa_circ_0048122 in predicting liver metastasis in CRC was probed in this work. This retrospective and multi-center investigation entailed exploration and identification stages with 158 and 176 patients. While RT-qPCR was employed to scrutinize hsa_circ_0048122 expression, Kaplan-Meier survival, and multivariate analyses were used to probe its prognostic impact in early-stage CRC and stage IV CRC cases, respectively. RESULTS: A strong correlation between liver metastases and hsa_circ_0048122 expression in stage IV CRC patients with a high hsa_circ_0048122 profile indicated a poor overall survival. Likewise, a high expression level of hsa_circ_0048122 appears as a potential predictor of liver metastases in patients' initial stages. CONCLUSIONS: Predicting liver metastasis can be plausibly facilitated using Hsa_circ_0048122 as a biomarker in early-stage CRC cases.
