Regular Use of Aspirin and Statins Reduces the Risk of Cancer in Individuals with Systemic Inflammatory Diseases.

Aspirin has shown potential for cancer prevention, but a recent large randomized controlled trial found no evidence for a reduction in cancer risk. Given the anti-inflammatory effects of aspirin, systemic inflammatory diseases (SID), such as osteoporosis, cardiovascular diseases, and metabolic diseases, could potentially modify the aspirin-cancer link. To investigate the impact of aspirin in people with SIDs, we conducted an observational study on a prospective cohort of 478,615 UK Biobank participants. Individuals with at least one of the 41 SIDs displayed a higher cancer risk than those without SIDs. Regular aspirin use showed protective effects exclusively in patients with SID, contrasting an elevated risk among their non-SID counterparts. Nonetheless, aspirin use demonstrated preventative potential only for 9 of 21 SID-associated cancer subtypes. Cholesterol emerged as another key mediator linking SIDs to cancer risk. Notably, regular statin use displayed protective properties in patients with SID but not in their non-SID counterparts. Concurrent use of aspirin and statins exhibited a stronger protective association in patients with SID, covering 14 common cancer subtypes. In summary, patients with SIDs may represent a population particularly responsive to regular aspirin and statin use. Promoting either combined or individual use of these medications within the context of SIDs could offer a promising chemoprevention strategy. SIGNIFICANCE: Individuals with systemic inflammatory diseases derive chemoprotective benefits from aspirin and statins, providing a precision cancer prevention approach to address the personal and public challenges posed by cancer.

Preoperative pectoralis muscle radiodensity as a risk factor for postoperative complications after thoracoscopic lobectomy for non-small cell lung cancer.

BACKGROUND: Skeletal muscle radiodensity is associated with postoperative complications in cancer. However, data on skeletal muscle radiodensity and postoperative complication risk in patients with non-small cell lung cancer (NSCLC) are scarce, and this study investigated the relationship between skeletal muscle radiodensity and postoperative complication risk in patients with NSCLC treated by thoracoscopic lobectomy. METHODS: Quantitative and qualitative measurements of the pectoralis muscle were performed on a single axial slice above the aortic arch in the precontrast computed tomography (CT) scan performed before surgery. Sex-specific cutoffs for the pectoralis muscle mass index (PMI) and pectoralis muscle radiodensity (PMD) were set at the lowest tertile. A Clavien-Dindo grade ≥ III within 30 days of the operation was considered as a major complication, and logistic regression analysis was performed to identify risk factors for postoperative complications. RESULTS: The records of 163 consecutive patients with NSCLC receiving first-line thoracoscopic lobectomy between March 2016 and October 2019 were retrospectively reviewed and the PMI was found to be positively correlated with PMD (P<0.001). The PMI and PMD were significantly higher in men than in women (both P<0.001), and 23 (14.1%) patients experienced major postoperative complications. The multivariate analysis showed that male sex (P=0.032), lower body mass index (BMI) (P=0.016), and low PMD (P=0.012) before surgery, but not low PMI, were independent risk factors for major postoperative complications. CONCLUSIONS: Skeletal muscle quality but not muscle mass predicts major complications after thoracoscopic lobectomy for NSCLC. Skeletal muscle measures from the preoperative CT scan may be used to stratify patients with NSCLC into risk categories that can guide clinical decision-making.

High expression of cell adhesion molecule 2 unfavorably impacts survival in non-small cell lung cancer patients with brain metastases.

BACKGROUND: Lung cancer is one kind of malignant tumor with a high risk for morbidity and mortality compared to other solid organ malignancies. Brain metastases occur in 30-55% of non-small cell lung cancer (NSCLC) patients. Prognosis of NSCLC patients with brain metastases is very poor. Our previous study showed that cell adhesion molecule 2 (CADM2) could regulate the development of brain metastasis in NSCLC cells. Therefore, the objective of the study is to evaluate the effect of CADM2 on the prognosis of NSCLC patients with brain metastases. METHODS: The expression of CADM2 was detected by quantitative real-time polymerase chain reaction (qRT-PCR) in the tissue of the primary tumor. Patients were followed up and overall survival (OS) was calculated. The relationships between CADM2 and clinicopathological features were analyzed using the chi-square test. Kaplan-Meier analysis was carried out to demonstrate the influence of CADM2 on the OS of patients. Univariate and multivariate Cox analyses were used to determine the prognosis of NSCLC patients with brain metastases. RESULTS: A total of 139 NSCLC patients with brain metastases from the Affiliated Cancer Hospital & Institute of Guangzhou Medical University, treated between January 2015 and December 2017 were evaluated retrospectively. The expression level of CADM2 in patients ranged from 1 to 17.2677, with a median of 6.0772. Chi-square analysis showed that CADM2 gene expression level was not significantly associated with gender, age, tumor location, histological subtype, tumor T stage, extracranial metastasis, or smoking status. However, CADM2 expression was notably associated with risk for lymph node metastasis. The results of the Kaplan-Meier analysis showed that high expression [CADM2 messenger RNA (mRNA) ≥6.0772] of CADM2 was markedly associated with poor prognosis. Univariate and multivariate Cox analyses demonstrated that CADM2 was an independent risk factor for survival in NSCLC patients with brain metastases (P<0.05). CONCLUSIONS: CADM2 expression is up-regulated and closely associated with disease progression and poor prognosis in NSCLC patients with brain metastases. CADM2 expression warrants special consideration given its potential prognostic significance that might help inform clinical decision making.

CircDUSP16 Contributes to Cell Development in Esophageal Squamous Cell Carcinoma by Regulating miR-497-5p/TKTL1 Axis.

BACKGROUND: The vital roles of circular RNAs in human cancers have been demonstrated. In this study, we aimed to investigate the functions of circDUSP16 in esophageal squamous cell carcinoma (ESCC) development. METHODS: Quantitative real-time polymerase chain reaction was executed for the expression levels of circDUSP16, DUSP16, miR-497-5p, and transketolase-like-1 (TKTL1) messenger RNA. Actinomycin D assay and RNase R digestion assay were used to determine the characteristics of circDUSP16. Cell Counting Kit-8 assay and colony formation assay were applied for cell proliferation. Transwell assay was performed to assess cell migration and invasion. The glycolysis level was evaluated using specific kits. Protein levels were measured by Western blot assay. RNA pull-down assay and dual-luciferase reporter assay were adopted to explore the relationships among circDUSP16, miR-497-5p, and TKTL1. Murine xenograft model was used to determine the role of circDUSP16 in ESCC in vivo. RESULTS: CircDUSP16 level was elevated in ESCC tissues, cells, and hypoxia-stimulated ESCC cells. Knockdown of circDUSP16 suppressed hypoxia-induced ESCC cell viability, colony formation, migration, invasion, and glycolysis. For mechanism analysis, circDUSP16 could positively regulate TKTL1 expression by sponging miR-497-5p in ESCC cells. Moreover, miR-497-5p inhibition restored the effects of circDUSP16 knockdown on the malignant behaviors of ESCC cells under hypoxia condition. MiR-497-5p overexpression suppressed hypoxia-induced ESCC cell progression by targeting TKTL1. In addition, circDUSP16 knockdown repressed the tumorigenesis of ESCC in vivo. CONCLUSIONS: CircDUSP16 knockdown suppressed hypoxia-induced ESCC cell growth, invasion, and glycolysis by regulating TKTL1 expression through sponging miR-497-5p.

MicroRNA-550a is associated with muscle system conferring poorer survival for esophageal cancer.

Background Esophageal cancer (ESCA) is one of the most common cancers in the digestive tract. Approximately 300000 people on an average die of ESCA per year worldwide. The determination of key microRNAs for the prognosis of ESCA is of indispensable significance in the clinical treatment. Methods The differentially expressed microRNAs were screened by analyzing The Cancer Genome Atlas (TCGA) database. By using the survival data of the database, we analyzed correlation between patients' survival time and miR-550a expression levels. Differential expression analysis and gene set enrichment analysis were performed using the targeted data. Results It was found that patients with high miR-550a expression levels had shorter survival time. Data mining and signal pathway enrichment analysis of TCGA database showed that abnormal miR-550a expressions affected the recurrence of tumors by the muscle system regulation. Conclusions Through the proposed investigation, miR-550a is found to be a potential biomarker as well as non-coding therapeutic target for esophagus cancer. These results suggest that miR-550a may serve as a therapeutic target and predictor for ESCA survival.

Overexpression of WRAP53 is associated with development and progression of esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly aggressive cancer whose underlying molecular mechanisms are poorly understood. The natural antisense transcript (NAT) WRAP53 regulates p53 expression and WRAP53 protein is a component of telomerase. NATs play key roles in carcinogenesis, and although WRAP53 is known to increase cancer cell survival, its role in ESCC clinicopathology is unknown. The aim of this study was to investigate WRAP53 expression in ESCC and to correlate it with clinicopathological characteristics. METHODS: WRAP53 mRNA and protein expression was measured by quantitative PCR (qRT-PCR) and western blotting, respectively, in 4 ESSC cells lines and in 45 paired ESCC and non-neoplastic esophageal mucosa tissues. To correlate WRAP53 protein expression with clinicopathological characteristics, immunohistochemistry (IHC) was performed on 134 ESCC and 85 non-neoplastic esophageal mucosa tissues. RESULTS: Expression of WRAP53 was detected in all ESCC cell lines and was upregulated in the ESCC tissues compared with the corresponding non-neoplastic tissues (P<0.01). More cells expressed WRAP53 protein in the ESCC tissues than in the non-neoplastic tissues (P<0.01). Overexpression of WRAP53 was significantly correlated with tumor infiltration depth (P = 0.000), clinical stage (P = 0.001), and lymph node metastasis (P = 0.025). Wrap53 expression was not correlated with age, gender, or tumor differentiation. CONCLUSION: This report indicates increased expression of WRAP53 in ESCC and that WRAP53 overexpression is correlated with tumor progression. WRAP53 may play a significant role in ESCC; accordingly, WRAP53 could be a useful biomarker for ESCC.

[Modulation of lung oxidant/antioxidant status by ischemic post-conditioning during ischemia/ reperfusion injury: experiment with rats].

OBJECTIVE: To investigate the effects of ischemic post-conditioning (IPO) on the lung endogenous oxidant-antioxidant system and nitric oxide level during the early stage of ischemia/reperfusion (I/R) injury. METHODS: Twenty four male Sprague-Dawley rats were randomly divided into 3 equal groups: sham-operation (S) group, I/R Group, undergoing ischemia by blocking the lung hilus for 1 h and then reperfusion for 30 min, IPO Group, undergoing blocking the lung hilus for 1 h and then 3 cycles of 10 s ischemia and 10 s reperfusion. Then the rats were killed with their lungs taken out. The levels of glutathione (GSH), nitric oxide (NO), malondialdehyde (MDA), xanthine oxidase (XO), and endogenous antioxidant enzymes, i. e, superoxide dismutase (SOD), and catalase (CAT), and activities of gultathionine peroxidase (GPX) and myeloperoxidase (MPO), a neutrophil accumulation marker, were measured respectively. RESULTS: In IPO group, Compared with I/R group, antioxidant systems such as the levels of SOD, CAT, GPX, and GSH of IPO Group were (41.4 +/- 4.4 ) U/mg, (19.5 +/- 1.6) U/mg, (168 +/- 13) U/mg, and (1.72 +/- 0.26) U/g, all significantly higher than those of I/R Group [(19.6 +/- 2.8) U/mg, (8.4 +/- 0.8) U/mg, (72 +/- 8) U/mg, and (0.89 +/-+/- 0.07) mg/g respectively, all P < 0.05); and the levels of XO, MPO, and MDA of Group IPO were (50 +/- 6) U/g, (5.0 +/- 0.5) U/g, and (0.91 +/- 0.08) nmol/mg respectively, all significantly lower than those of I/R Group [(83 +/- 8) U/g, (7.6 +/- 0.7) U/g and (1.58 +/- 0.17) nmol/mg respectively, all P < 0.05). The endogenous NO level of IPO Group was (93 +/- 7) micromol/g, significantly higher than that of I/R Group [(22 +/- 4) micromol/g, P < 0.01]. CONCLUSION: Post-conditioning at onset of reperfusion reduces lung I/R injury. The lung protection of IPO may be mediated, in part, by inhibiting the oxidant generation and oxidizing, and may be associated with the increasing of the endogenous NO level.