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Cancer cell-derived exosomes regulate tumor growth and progression. However, the effects of exosomes and its contents on head and neck squamous cell carcinoma (HNSCC) and its underlying mechanisms remain unclear. Here, we found HNSCC displayed a dysregulation of exosomes biogenesis. miR-185-3p was one of the most upregulated exosome-derived miRNAs in HNSCC. Functional assay showed that RAB25 is a direct downstream target of miR-185-3p. miR-185-3p/RAB25 signaling controlled tumor progression and correlated with disease prognosis. Targeting miR-185-3p/RAB25 significantly inhibited tumor growth and promoted drug response to chemotherapy. To conclude, the findings demonstrate exosomal miR-185-3p promotes tumor growth by mediating RAB25 that could be effectively targeted for HNSCC treatment. [ABSTRACT FROM AUTHOR]

Background and Objective: Tools for the non-invasive assessment of colorectal cancer (CRC) prognosis have profound significance. Although plasma coagulation tests have been investigated in a variety of tumours, the prognostic value of the prothrombin time (PT) and activated partial thromboplastin time (APTT) in CRC has not been discussed. Our study objective was to explore the prognostic significance of preoperative PT and APTT in CRC patients. Patients and Methods: A retrospective analysis of preoperative coagulation indexes including PT, PTA, INR, APTT, FIB, TT, PLT, NLR and PLR in 250 patients with CRC was performed. Kaplan–Meier and multivariate Cox regression analysis were used to demonstrate the prognostic value of these preoperative coagulation indexes. Results: The overall survival (OS, p< 0.05) and disease-free survival (DFS, p< 0.05) of CRC patients with lower PT and APTT levels were significantly prolonged. Based on univariate analysis, PT levels (p< 0.001, p< 0.001), PTA levels (p=0.001, p=0.001), APTT levels (p=0.001, p< 0.001), INR levels (p< 0.001, p< 0.001), fibrinogen levels (p=0.032, p=0.036), tumour status (p=0.005, p=0.003), nodal status (p< 0.001, p< 0.001), metastasis status (p< 0.001, p< 0.001) and TNM stages (p< 0.001, p< 0.001) were remarkably associated with DFS and OS. Multivariate Cox regression analysis suggested that the levels of PT (HR: 2.699, p=0.006) and APTT (HR: 1.942, p=0.015), metastasis status (HR: 2.091, p= 0.015) and TNM stage (HR: 7.086, p=0.006) were independent predictors of survival in CRC. In the whole cohort, the enrolled patients were then divided into three groups according to their PT and APTT levels. The OS and DFS differed notably among the low-risk (PT< 11.85 sec and APTT< 25.85 sec), medium-risk (PT≥ 11.85 sec or APTT≥ 25.85 sec), and high-risk (PT≥ 11.85 sec and APTT≥ 25.85 sec) groups. Conclusion: Elevated levels of preoperative PT and APTT were predictors of poor outcomes in CRC patients. Moreover, the combination of preoperative PT and APTT can be a new prognostic stratification approach for more precise clinical staging of CRC. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to propose a prognostic scoring system based on preoperative serum apolipoprotein A-1 and C-reactive protein (ApoA-1 and CRP, AC score) levels and to evaluate the prognostic value of these markers in patients with hepatocellular carcinoma (HCC).Methods: In all, 539 consecutive cases diagnosed with HCC from 2009 to 2012 at Sun Yat-sen University Cancer Center were analysed. The characteristics and levels of pretreatment lipids (ApoA-1, apolipoprotein B (Apo-B), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TGs)) and CRP were reviewed and determined by univariate and multivariate Cox hazard models. Then, the AC score was proposed, which combines two independent risk factors (ApoA-1 and CRP).Results: The optimal cut-off points in our study were determined according to established reference ranges. Patients with decreased ApoA-1 levels (< 1.090 g/L) and increased CRP levels (≥3.00 mg/L) exhibited a significantly poor overall survival (OS) and disease-free survival (DFS). The AC score was calculated as follows: patients with decreased ApoA-1 and elevated CRP were given a score of 3, patients with only one of these abnormalities were given a score of 2, and those with no abnormalities were given a score of 1. Patients with a higher AC score showed more progressive disease and a poorer prognosis. This was observed not only in the entire cohort (for OS, P < 0.001; for DFS, P < 0.001) but also in the subgroups stratified by pathological stage (stage I-II and stage III-IV). The discriminatory ability of the AC score in HCC was assessed according to the AUC values. The AUC value of the AC score (AUC: 0.676, 95% CI: 0.629-0.723, P < 0.001) was higher than that of AFP. In addition, the combination of the AFP and AC scores (AUC: 0.700, 95% CI: 0.655-0.745, P < 0.001) was superior to the AFP and AC scores alone.Conclusions: The AC score is a significant valuable predictor of OS and DFS and could more accurately differentiate the prognosis of HCC patients. As this study is a retrospective analysis, the value of the AC score should be validated in large prospective trials. [ABSTRACT FROM AUTHOR]

Oesophageal squamous cell carcinoma (ESCC) is a common type of carcinoma. Hypoxia is associated with chemo- and radio-resistance, which may lead to a poor prognosis. Hypoxia-inducible factor-1α (HIF-1α) is the main transcriptional regulator of the cellular response to low oxygen levels. Moreover, it can trigger the expression of critical genes, including glucose transporter protein type 1 (GLUT1). The aim of the present study was to evaluate the roles of HIF-1α and GLUT1 in ESCC and their usefulness as prognostic markers. HIF-1α and GLUT1 were measured in four ESCC cell lines, namely Eca109, KYSE150, TE-1 and TE-10, by western blotting following culture under normoxic and hypoxic conditions. In addition, xenograft tumors were established in mice using normoxic and hypoxic Eca109 cells and the chemosensitivity of the xenografts to 5-fluorouracil (5-FU) was evaluated. Furthermore, HIF-1α and GLUT1 were analysed by immunochemistry in the tumor tissues of patients with ESCC and the associations of their expression levels with clinicopathological parameters were investigated. The results revealed that HIF-1α and GLUT1 protein expression was weak in all four cell lines under a normoxic atmosphere but increased following culture in a hypoxic environment. In vivo, 5-FU inhibited tumor growth more strongly in normoxic Eca109 ×enografts than hypoxic Eca109 ×enografts. Higher levels of apoptosis were also detected in the normoxic Eca109 ×enografts via western blotting and TUNEL analysis. In patients with ESCC, HIF-1α expression was associated with advanced ESCC while GLUT1 expression was associated with the sex of the patients. Multivariate analysis demonstrated that HIF-1α and GLUT1 were negatively associated with progression-free survival (PFS) and overall survival (OS). Additionally, a combination of HIF-1α and GLUT1 expression was a predictor of RFS and OS in patients with ESCC without lymph node metastasis but not those with lymph node metastasis. The study demonstrated that HIF-1α and GLUT1 were strongly expressed in vitro and in xenograft models when cells were exposed to hypoxia. The simultaneous high expression of HIF-1α and GLUT1 was associated with poorer survival, and may play an important role in ESCC chemoresistance and the prognosis of ESCC. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC), a prevalent primary malignant tumor, is notorious for its high mortality rate. Despite advancements in HCC treatment, patient outcomes remain suboptimal. This study endeavors to assess the potential prognostic significance of POLH-AS1 in HCC. Methods: In this research, we gathered RNA-Seq information from individuals with HCC in The Cancer Genome Atlas (TCGA). We analyzed the levels of POLH-AS1 expression in both HCC cells and tissues using statistical tests. Additionally, we examined various prognostic factors in HCC using advanced methodologies. Furthermore, we employed Spearman's rank correlation analysis to examine the association between POLH-AS1 expression and the tumor's immune microenvironment. Finally, the functional roles of POLH-AS1 in HCC were validated in two HCC cell lines (HEP3B and HEPG2). Results: Our analysis revealed elevated POLH-AS1 expression across various cancers, including HCC, with heightened expression correlating with HCC progression. Notably, POLH-AS1 expression emerged as a potential biomarker for HCC patient survival and prognosis. Mechanistically, we identified the involvement of POLH-AS1 in tumorigenesis pathways such as herpes simplex virus 1 infection, interactions with neuroactive receptors, and the cAMP signaling pathway. Lastly, inhibition of POLH-AS1 was discovered to hinder the proliferation, invasion and migration of HEP3B and HEPG2 HCC cells. Conclusions: POLH-AS1 emerges as a promising prognostic biomarker and therapeutic target for HCC, offering potential avenues for enhanced patient management and treatment strategies. [ABSTRACT FROM AUTHOR]