Secondary primary lung cancer after esophageal cancer: a population-based study of 44,172 patients.

BACKGROUND: The present study aimed to assess the survival, incidence, and characteristics of secondary primary lung cancer (SPLC) after esophageal cancer (EC-LC). METHODS: The patients with esophageal cancer (EC) who developed SPLC and patients with first primary lung cancer (LC-1) were retrospectively reviewed in the Surveillance, Epidemiology, and End Results 18 registries covering 2000-2016. Overall survival and characteristics were compared between patients with EC-LC and patients with LC-1. The independent relation between a history of EC and death was evaluated by calculating hazard ratios in multivariate Cox regression analysis propensity score-matching analysis, and multiple imputation for cases with missing information. RESULTS: In comparison with the general population, the patients with EC had a higher risk for developing secondary primary lung cancer (SIR =1.86, 95% confidence interval (CI): 1.69-2.05). A history of EC was found to be an independent risk factor of death for lung squamous carcinoma (LUSC) and lung adenocarcinoma (LUAD) patients in localized stage based on multivariate Cox regression analysis, propensity score-matching analysis and multiple imputation. CONCLUSIONS: There is a significantly increased risk of secondary primary lung cancer in EC survivors and a history of EC adversely affects overall survival in individuals who subsequently develop localized LUSC and LUAD. Clinicians should moderately strengthen lung tissue protection during the management of EC patients.

Double-stranded RNA-dependent kinase PKR activates NF-κB pathway in acute pancreatitis.

The activation of transcription factor nuclear factor kappa B (NF-κB) occurs early in acute pancreatitis (AP) simultaneously with intracellular trypsinogen activation. Double-stranded RNA-dependent kinase (PKR) promotes the activation of NF-κB and the production of pro-inflammatory factors including tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). The rat and rat pancreatic AR42J cells were treated by cerulein to establish AP models, showing PKR increased. TNF-α, IL-6 and lactate dehydrogenase (LDH) in AP pancreatic tissues and cerulein-treated AR42J cells increased, while PKR knockdown in AR42J cells reversed cerulein-induced inflammatory response and pancreatic cell injury. In addition, inhibitor of kappa B kinase α (IKKα), phosphorylated P65 (p-P65), P65 increased in cerulein-treated AR42J cells. Meanwhile, in cerulein-treated AR42J cells, interaction between PKR and IKKα, as well as the co-localization and nuclear accumulation of PKR and P65, were detected. Furthermore, cerulein induced the phosphorylation and nuclear translocation of P65, which indicated the activation of NF-κB, while PKR knockdown hindered NF-κB activation to alleviate pancreatic cell injury. In summary, PKR might promote NF-κB activation via facilitating its phosphorylation and nuclear translocation, thus accelerated inflammatory response and pancreatic cell injury in AP, implying a novel molecular target for the treatment of AP.

Elevated NDC1 expression predicts poor prognosis and correlates with immunity in hepatocellular carcinoma.

Background: NDC1 was identified to be a tumor-promoting factor in non-small cell lung cancer and cervical cancer. However, no report had clarified the relationship between NDC1 and hepatocellular carcinoma (HCC). In this paper, we explored the expression and potential functions of NDC1 in HCC for the first time through the rational application of bioinformatics and relevant basic experiments. Methods: NDC1-related expression profiles and clinical data of HCC patients were collected from The Cancer Genome Atlas (TCGA) database, which were verified via quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Univariate and multivariate Cox regression analyses were used to identify NDC1 as an independent factor for HCC prognosis, and NDC1-related signaling pathways were determined by gene set enrichment analysis (GSEA). Furthermore, we deeply probed the potential links of NDC1 to immunity and immune response. Finally, the bioeffects and underlying mechanisms of ectopic NDC1 overexpression and depletion were determined in HepG2 cells by immunoblotting, flow cytometry, Cell-Counting-Kit-8 (CCK-8), and EDU (5-Ethynyl-2'-deoxyuridine). Results: Up-regulated expression of NDC1 was detected by means of the TCGA database, which was consistent with the results obtained from further qRT-PCR, immunohistochemistry and the CPTAC database. Kaplan-Meier (K-M) survival analysis revealed a worse prognosis in HCC patients with high NDC1 expression. Besides, NDC1 was certified to be closely linked to tumor histologic grade, clinical stage and T stage. Moreover, univariate and multivariate Cox regression analyses defined NDC1 as an independent element for HCC prognosis. NDC1-related signaling pathways, utilizing GSEA analysis, were subsequently found out. What's more, NDC1 expression was detected to be enormously associated with microsatellite instability (MSI), immune cell infiltration, immune checkpoint molecules and immune cell pathways. As for immunotherapy, we discovered that different risk groups tended to have different immune checkpoint inhibitor responses, which indicated crucial implication value of NDC1 for HCC immunotherapy. More interestingly, we observed that the overexpression of NDC1 could promote the migration and invasion of HCC cells. Conclusions: Our article demonstrated that NDC1 might serve as a valuable predictor in the prognosis and immunotherapy of HCC. NDC1 played an oncogenic role in HCC.

Clinical value of BISAP score combined with CRP and NLR in evaluating the severity of acute pancreatitis.

To investigate the clinical value of bedside index for severity in acute pancreatitis (BISAP) score combined with serum C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) in predicting the severity of early acute pancreatitis. A total of 113 patients with acute pancreatitis admitted to the Department of Gastroenterology, Second Affiliated Hospital of Nantong University from September 2019 to September 2022 were retrospectively collected and divided into mild acute pancreatitis group (51 cases), moderately severe acute pancreatitis group (32 cases) and severe acute pancreatitis group (30 cases) according to the severity of the disease. The general clinical data, laboratory test indicators, and imaging data within 72 hours were collected and compared among the 3 groups. The sensitivity, specificity, and accuracy of BISAP score, BISAP combined with CRP, BISAP combined with NLR, and BISAP combined with CRP and NLR in predicting the severity of acute pancreatitis were analyzed by receiver operating characteristic curve. 1. BISAP score (0.9608 ± 0.1119, 1.688 ± 0.1225, 2.6 ± 0.1135), CRP (74.77 ± 8.336, 142.9 ± 11.44, 187.6 ± 13.04), and NLR (8.063 ± 0.7781, 13.69 ± 1.023, 18.06 ± 1.685) increased sequentially in mild acute pancreatitis group, moderately severe acute pancreatitis group, and severe acute pancreatitis group, and the differences in BISAP score, CRP and NLR among the 3 groups were statistically significant (P < .05). BISAP score was positively correlated with CRP and NLR (R = 0.5062, 0.5247, P < .05). The area under the receiver operating characteristic curve of BISAP score, CRP, NLR, BISAP combined with NLR, and BISAP combined with CRP in predicting the severity of acute pancreatitis were 0.885, 0.814, 0.714, 0.953, respectively. The specificity and sensitivity of combined diagnosis were higher than those of BISAP score or CRP and NLR alone. BISAP score combined with CRP and NLR can effectively evaluate the severity of acute pancreatitis, and their combination has a higher predictive value for early severity assessment.

Elevated double-strand break repair protein RAD50 predicts poor prognosis in hepatitis B virus-related hepatocellular carcinoma: A study based on Chinese high-risk cohorts.

Objective: Increasing evidence indicates that RAD50, which is involved in the repair process of DNA double-strand break (DSB), is also involved in cancer outcomes. However, its role in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains unclear. This study was designed to investigate the expression of RAD50 and its prognostic value in HBV-related HCC patients. Methods: 107 and 100 patients with HBV-related HCC from the Affiliated Hospital of Youjiang Medical University of Nationalities (AHYMUN) and the Affiliated Hospital of Nantong University (AHNU), respectively, were enrolled in the study. The distribution of the categorical clinical-pathological data and the levels of RAD50 expression were compared with a χ2 test. Immunohistochemistry (IHC) staining of RAD50 was performed. A partial likelihood test based on univariate and multivariate Cox regression analysis was developed to address the influence of independent factors on disease-free survival (DFS) and overall survival (OS). The Oncomine online database was used to analyse and validate the differential expression of RAD50. The Kaplan-Meier method and a log-rank test were performed to assess the influence of RAD50 on survival at different levels. Results: RAD50 was highly expressed in HCC tissues compared to normal tissues and was significantly correlated with OS in the Cancer Genome Atlas (TCGA) cohort. The validation analysis indicated that significantly increased levels of RAD50 were expressed in HCC tissues in the two independent cohorts. In addition, HCC patients with elevated RAD50 expression levels showed poor OS and DFS in the AHYMUN cohort and decreased OS and DFS in the AHNTU cohort. Conclusion: In conclusion, our study reveals that elevated RAD50 expression is significantly correlated with cancer progression and poor survival in HBV-related HCC patients. These data suggest that RAD50 may act as an oncogene and may serve as a promising target for the therapy of HBV-related HCC patients.

Runt-related transcription factor 2 (RUNX2) inhibits apoptosis of intestinal epithelial cells in Crohn's disease.

Apoptosis in intestinal epithelial cells (IECs) prevents the development of Crohn's disease (CD), a type of inflammatory bowel disease (IBD). Runt-related transcription factor 2 (Runx2) inhibits apoptosis in osteosarcoma-derived U2OS cells via down-regulating the transcriptional activity of p53. However, the expression and function of Runx2 in CD remain unclear. In this study, Runx2 protein levels were decreased in the intestinal epithelial cells (IECs) of CD patients and in a mouse 2, 4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis model; in contrast, the expression levels of p53 and Bax, a p53-target gene, were increased. In a TNF-α-treated HT29 cell colitis model, the down-regulation of Runx2 was accompanied by the up-regulation of apoptotic markers, including cleaved caspase-3 and Bax. Furthermore, Runx2 overexpression effectively decreased TNF-α-induced Bax and cleaved caspase-3 expression levels. In conclusion, our data indicated that Runx2 might protect IECs from apoptosis in CD, thus revealing a novel molecular target for treating CD.

Activating transcription factor 3 promotes intestinal epithelial cell apoptosis in Crohn's disease.

Intestinal epithelial cell (IEC) apoptosis plays a vital role in the pathogenesis of Crohn's disease (CD), which is an inflammatory bowel disease (IBD). Activating transcription factor 3 (ATF3) modulates apoptosis under stress via regulating the p53 pathway. However, the expression and function of ATF3 in CD are unclear. In the present study, ATF3, p53, and p53 target gene Bax expression increased in CD patients; a mouse 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced CD model; and a TNF-α-treated HT29 cell colitis model. ATF3 knockdown effectively decreased TNF-α-induced p53 and Bax expression, as well as inhibited the apoptosis of HT29 cells. Additionally, ATF3 enhanced the stability and transcription activity of p53 via interacting with p53. In summary, these data indicated that ATF3 might promote IEC apoptosis in CD via up-regulating the stability and transcription activity of p53, implying a novel molecular target for CD therapy.