We identified specific genetic and mutation features of HCCs associated with aflatoxin exposure, including mutations in ADGRB1, compared to HCCs from general populations. We associated these mutations with increased vascularization and expression of PD-L1 in HCC tissues. These findings might be used to identify patients with HCC due to aflatoxin exposure, and select therapies.
Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related death in China and has limited effective therapeutic options except for early surgery, since the underlying molecular mechanism driving its precursor lesions towards invasive ESCC is not fully understood. Cellular senescence is the state of the permanent growth arrest of a cell, and is considered as the initial barrier of tumor development. Human differentiated embryo chondrocyte expressed gene 1 (Dec1) is an important transcription factor that related to senescence. In this study, DEC1 immunohistochemical analysis was performed on tissue microarray blocks constructed from ESCC combined with adjacent precursor tissues of 241 patients. Compared with normal epithelia, DEC1 expression was significantly increased in intraepithelial neoplasia and DEC1 expression was significantly decreased in ESCC in comparison with intraepithelial neoplasia. In vitro , DEC1 overexpression induced cellular senescence, and it inhibited cell growth and colony formation in ESCC cell line EC9706. Fresh esophagectomy tissue sections from five ESCC patients were detected by immunohistochemistry of DEC1 and senescence-associated β-galactosidase (SA-β-Gal) activity, and strongly positive expression of DEC1 was correlated to more senescent cells in these fresh tissue sections. Kaplan – Meier method analysis of the 241 patients revealed that DEC1 expression levels were significantly correlated with the survival of ESCC patients after surgery. The expression levels of DEC1 were also correlated with age, tumor embolus, depth of invasion of ESCC, lymph metastasis status and pTNMs. These results suggest that DEC1 overexpression in precursor lesions of ESCC is a protective mechanism by inducing cellular senescence in ESCC initiation, and DEC1 may be a potential prognostic marker of ESCC.
Background Partial hepatectomy is the first option for intrahepatic mass-forming cholangiocarcinoma (IMCC) treatment, which would prolong survival. The main reason for the poor outcome after curative resection is the high incidence of early recurrence (ER). The aim of this study was to investigate the combined predictive performance of qualitative and quantitative magnetic resonance imaging (MRI) features and prognostic immunohistochemical markers for the ER of IMCC. Methods Forty-seven patients with pathologically proven IMCC were enrolled in this retrospective study. Preoperative contrast-enhanced MRI and post-operative immunohistochemical staining of epidermal growth factor receptors (EGFR), vascular endothelial growth factor receptor (VEGFR), P53 and Ki67 were performed. Univariate analysis identified clinic-radiologic and pathological risk factors of ER. Radiomics analysis was performed based on four MRI sequences including fat suppression T2-weighted imaging (T2WI/FS), arterial phase (AP), portal venous phase (PVP), and delayed phase (DP) contrast enhanced imaging. A clinicoradiologic-pathological (CRP) model, radiomics model, and combined model were developed. And ROC curves were used to explore their predictive performance for ER stratification. Results Enhancement patterns and VEGFR showed significant differences between the ER group and non-ER group ( P = 0.001 and 0.034, respectively). The radiomics model based on AP, PVP and DP images presented superior AUC (0.889, 95% confidence interval (CI): 0.783–0.996) among seven radiomics models with a sensitivity of 0.938 and specificity of 0.839. The combined model, containing enhancement patterns, VEGFR and radiomics features, showed a preferable ER predictive performance compared to the radiomics model or CRP model alone, with AUC, sensitivity and specificity of 0.949, 0.875 and 0.774, respectively. Conclusions The combined model was the superior predictive model of ER. Combining qualitative and quantitative MRI features and VEGFR enables ER prediction, thus facilitating personalized treatment for patients with IMCC.
Background: The aim of this study was to evaluate the significance of spread through air spaces (STAS) in early lung adenocarcinomas after radical lobectomy and lymphadenectomy. Methods: A total of 242 patients with lung adenocarcinomas less than 4 cm (8th pStage I) were selected from the lung cancer patients surgically treated from January, 2009 to September, 2011. Pathological review focused on STAS as well as histological subtypes, blood vessel & neural invasion, pathological tumor size etc. Recurrence or disease-free survival (DFS) and overall survival (OS) were compared between patients as stratified by STAS and tumor size. Results: STAS was observed in 33.47% (81/242) patients, which was significantly correlated with histological predominant subtype (χ 2 =25.903, P=0.093×10 −3) and differentiation grade (χ 2 =23.986, P=0.025×10 −3). Patients with STAS (+) showed a comparable PFS (P=0.268) and OS rates (P=0.100) in all stage I cases, but a significant lower PFS (P=0.029) and OS (P=0.013) in tumors within 2< tumors ≤4 cm. Multivariate analysis revealed STAS to be an independent worse prognostic factor in lung adenocarcinomas within 2< tumors ≤4 cm, both for PFS (P=0.004) and OS (P=0.002) , while no significant difference was found in patients with tumors ≤2 cm (PFS, P=0.537; OS, P=0.448), after adjusting by other clinicopathological parameters as age, gender, smoking etc. Conclusions: Presence of STAS was a significant worse predictor for pStage I patients with lung adenocarcinoma >2 cm who underwent radical lobectomy, while it is not significant in patients with tumor ≤2 cm. These findings may be helpful in assessing postoperative therapy stratified by tumor size and STAS status.
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