Abstract LINC00624 is a long noncoding RNA (lncRNA) which was seldom investigated before. The goal of our study is to clarify the expression and underlying network of LINC00624 in hepatocellular carcinoma (HCC). Here, both HCC and normal living cell lines were employed. Real‐time quantitative PCR and western blot were used to determine the pattern of genes and proteins. Colony formation, flow cytometry and western blot tests were used to determine cell proliferation and apoptosis, respectively. Dual luciferase was used to verify molecule‐molecule interactions. LINC00624 expression was increased in HCC cell lines and miR‐342‐3p was decreased. Elimination of LINC00624 increased proliferation while decreasing cell apoptosis. LINC00624 acted as a molecular sponge for miR‐342‐3p, hence facilitating DNAJC5 expression. Functional tests demonstrated that miR‐342‐3p suppression could reverse the effect of LINC00624 silence and overexpression of DNAJC5 significantly mitigated the biological consequences of miR‐342‐3p. These finding demonstrated that LINC00624 aggravated HCC progression by modulating proliferation and apoptosis via targeting miR‐342‐3p/DNAJC5 axis. These data support that inhibition of LINC00624 may a potential treatment strategies of HCC.
Objective
To investigate the situation of cardiovascular diseases in patients with cancer, and to explore the effect of those diseases on the diagnosis and treatment of cancerous patients.
Methods
We collected the medical records of cancer patients who need consultation from January 1, 2013 to December 31, 2017 in Peking University Cancer Hospital, and screened the cases of cardiovascular diseases. The clinical records of the patients in this group were analyzed retrospectively, and the effects of those diseases on the diagnosis and treatment of tumor were discussed.
Results
From 1 323 cases, 371 cases (28.0%) with cardiovascular disease were selected. Among them, 237 were male (63.9%). The age range is 16-88 years old. The primary tumor types include 97 cases of lung cancer, 45 cases of gastric cancer, 42 cases of lymphoma, 41 cases of colorectal cancer, 32 cases of esophageal cancer, 12 cases of cholangiocarcinoma / gallbladder carcinoma, 10 cases of breast cancer, 10 cases of liver cancer, 9 cases of pancreatic tumor, 8 cases of malignant melanoma, and 65 cases of other tumors. The tumor stage was 69 cases (18.6%) in stage Ⅰ, 52 cases in stage Ⅱ (14.0%), 77 cases in Ⅲ stage (20.8%), 131 cases in Ⅳ stage (35.3%), 42 cases (11.3%) in unknown stages. The cardiovascular diseases include: 89 cases of thromboembolic disease (24.0%), 75 cases of arrhythmia (20.2%), peripheral vascular disease and stroke in 65 cases (17.5%), 54 cases of coronary heart disease (14.6%), dysfunction cardiac/heart failure in 32 cases (8.6%), 22 cases of hypertension (5.9%), 6 patients with pulmonary hypertension (1.6%), 5 cases of valvular disease (1.3%), and 23 cases of pericardial disease and others (6.2%). Risk assessment before antitumor treatment: 116 cases (31.3%). The treatment of the complications of antitumor treatment: 132 cases (35.6%). The diagnosis and treatment of cardiovascular disease: 123 cases (33.2%). Cardiovascular diseases deciding tumor diagnosis and treatment: 298 cases (80.3%); no influence: 56 cases (15.1%); uncertain: 17 cases (4.6%).
Conclusions
Cardiovascular diseases are common associated with cancer. Most of them directly affect the formulation of the tumor diagnosis and treatment program.
Key words:
Neoplasms; Cardiovascular disease
High recurrence rate in HCC is the primary cause of the poor prognosis after hepatectomy. Therefore, in this study, we aimed to construct a gene signature for predicting the recurrence rate in HCC. The mRNA expression profiles and clinical information of HCC patients from GEO and TCGA databases were used, and ferroptosis-related gene list was obtained from the FerrDb database. We identified 39 ferroptosis-related genes (FDEGs) that were differentially expressed between HCC samples and normal tissues from the GSE14520 dataset. The univariate and multivariate Cox regression analyses were employed to construct a prognostic signature. Seven FDEGs (MAPK9, SLC1A4, PCK2, ACSL3, STMN1, CDO1, and CXCL2) were included to construct a risk model, which was validated in the TCGA dataset. Patients in high-risk groups exhibited a significantly poor prognosis compared with patients in low-risk groups in both the training set (GSE14520 cohort) and the validation set (TCGA cohort). Multivariate cox regression analyses demonstrated that the 7-gene signature was an independent risk factor for RFS in HCC patients. KEGG analysis showed that FDEGs were mainly enriched in Ferroptosis, Hepatocellular carcinoma pathway, and MAPK signaling pathway. GSEA analysis suggested that the high-risk group was correlated with multiple oncogenic signatures and invasive-related pathways. These results indicated that this risk model can accurately predict recurrence after hepatectomy and offer novel research directions for personalized treatment in HCC patients.
Disabled-2 (DAB2), a potential tumor suppressor, plays an in important role in cancer development and cellular differentiation. Its lower expression levels have founded in many cancers. In addition, DAB2 is involved in multiple signaling pathways, including TGF-β and Wnt signal pathways. Gastric cancer (GC) is a common gastrointestinal malignant tumor. Nonetheless, the role of DAB2 in GC remains unclear.Thirty-seven clinical specimens of GC tissues and adjacent non-tumor tissues were examined by immunohistochemistry. Proteins were extracted from two of them to perform Western blot analysis. Then, CMV-MCS-3FLAG-SV40-DAB2 and si-DAB2 were transfected into MGC and SGC cell line, respectively. The migration of GC cells was evaluated by transwell migration assay. And, the expression of migration related proteins was detected by Western blot and immunofluorescence (IF).Eighty-six percent (32/37) of patients DAB2 staining was reduced in GC tissues compared to adjacent normal tissues. Further studies showed that in six human GC cell lines, the level of DAB2 expression was lower than normal gastric epithelial cells, and that DAB2 was closely related to cell migration in vitro. In DAB2 silenced cells, the Wnt/β-catenin signaling was increased and the Hippo-YAP pathway was affected. In addition, lower DAB2 level led to nuclear translocation of β-catenin and Yap.The lower expression of DAB2 regulates cell migration in GC via interfering with the Wnt and Hippo signaling pathway. Our findings suggested that DAB2 played an important role in the migration of GC.
Breast cancer antiestrogen resistance 4 (BCAR4) is a novel long noncoding RNA. It was originally identified in a screen for genes responsible for the development of resistance to antiestrogens in breast cancer cells and plays a major role in various tumors. However, the clinical diagnostic role of BCAR4 in tumors is not completely understood. This current meta-analysis aimed to comprehensively explore the potential role of BCAR4 as a prognostic biomarker in a number of cancers. Five public databases PubMed, EMBASE, Web of Science, Wiley Online Library, and Medline were used to search for articles. Nine studies comprising 1,293 patients were included in this meta-analysis. The results of analysis showed that BCAR4 expression in human cancer was significantly associated with poor overall survival (hazard ratio [HR] = 1.98, confidence interval [CI]: [1.71-2.29]), p < 0.00001, and high BCAR4 expression was associated with clinical stage (OR and its 95% CI was 3.30 [1.99-5.46], p < 0.00001), distant metastasis (OR = 3.83, 95% CI: 2.15-6.82, p < 0.00001), and lymph node metastasis (OR and its 95% CI was 2.91 [1.62-5.25], p = 0.0004) in patients with cancer. Furthermore, the results revealed the prognostic significance of BCAR4 in gastrointestinal malignancy, breast cancer, and osteosarcoma (HR and its 95% CI were 2.05 [1.56-2.68], p < 0.00001; 1.78 [1.46-2.16], p < 0.00001; and 2.47 [1.41-4.34], p < 0.00001, respectively). This meta-analysis indicated the potential value of BCAR4 as a biomarker for predicting a poor prognosis in patients with cancer.
The hormone αKlotho regulates lifespan in mice, as knockouts die early of what appears to be accelerated aging due to hyperphosphatemia and soft tissue calcification. In contrast, the overexpression of αKlotho increases lifespan. Given the severe mouse phenotype, we generated zebrafish mutants for αklotho as well as its binding partner fibroblast growth factor-23 (fgf23). Both mutations cause shortened lifespan in zebrafish, with abrupt onset of behavioral and degenerative physical changes at around 5 months of age. There is a calcification of vessels throughout the body, most dramatically in the outflow tract of the heart, the bulbus arteriosus (BA). This calcification is associated with an ectopic activation of osteoclast differentiation pathways. These findings suggest that the gradual loss of αKlotho found in normal aging might give rise to ectopic calcification.
Background: Cuproptosis, a novel form of cell death regulated by protein lipoylation and implicated in mitochondrial metabolism. However, the impact of the cuproptosis-related gene γ-glutamylcysteine synthetase (GCSH) on endometrial cancer (EC) prognosis, tumor immune microenvironment, and therapeutic response remains to be further researched. Methods: The differential expression of GCSH between endometrial cancer and normal tissues was analyzed using multiple public databases. Additionally, cancer and adjacent tissues were prospectively collected from 17 EC patients, and immunohistochemical analysis was performed to further investigate GCSH expression differences. The relationship between GCSH and the prognosis and clinicopathological characteristics of EC patients was evaluated, and a nomogram was constructed to predict patient survival based on GCSH expression. Then, Gene set variation analysis (GSVA) was utilized to explore the potential biological functions of GCSH in EC. The impact of GCSH on the tumor microenvironment (TME) was estimated. Finally, the effect of GCSH on the response to immunotherapy and chemotherapeutic drugs in EC was investigated. Results: The expression of GCSH was significantly upregulated in EC. High GCSH expression was associated with poor prognosis in EC patients. Enrichment analysis showed that high GCSH was associated with immune suppression. Furthermore, high GCSH was found to be associated with a non-inflamed TME, leading to decreased infiltration levels of immune cells. Finally, it was observed that patients with high GCSH were insensitive to both immunotherapy and chemotherapeutic drugs. Conclusion: This study revealed the role of GCSH in TME, response to therapy, and clinical prognosis in EC, which provided novel insights for the therapeutic application in EC.
Zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) is a long non-coding RNA, which has found to unregulated in various kinds of cancer. This meta-analysis was conducted to demonstrate the association between ZEB1-AS1 expression levels and clinical outcome or prognosis of cancer patients.10 studies with 783 cancer patients were included in this meta-analysis by retrieving 5 databases (PubMed Central, EMBASE, Cochrane Library, Wiley Online Library and Medline).The result showed that overexpression of ZEB1-AS1 is significantly correlated with poor OS (Hazard ratio, HR=2.45, 95% confidence interval, CI: 1.89-3.16). ZEB1-AS1 expression levels were also associated with clinicopathological parameters including lymph node metastasis (Yes vs. No; OR=4.00, 95%CI: 2.23-7.17, P<0.00001), histologic differentiation (Moderate + poor vs. Well; OR=2.72, 95% CI: 1.69-4.37, p<0.0001), tumor metastasis and invasion (Yes vs. No; OR =2.52, 95%CI: 1.12-5.68, P=0.03) and TNM stage (III+IV vs. I+II; OR=2.76, 95 %CI 1.46-5.21, P=0.002). However, ZEB1-AS1 expression was not significantly associated with patients' gender (Male vs. Female; OR=1.20, 95% CI: 0.87-1.66; P=0.27).This meta-analysis indicated the potential value of ZEB1-AS1 as a biomarker for predicting a poor prognosis in patients with cancer.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)