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OBJECTIVE: GRWD1 (glutamate-rich WD40 repeat containing 1) is a multifunctional protein involved in multiple cellular regulatory pathways, particularly those associated with cell growth control. GRWD1 is represented as a potential oncogene in several cancers, however, the function and mechanism of GRWD1 in the development of colon cancer are still unknown. MATERIALS AND METHODS: IHC was used to detect the expression of GRWD1 in colon carcinoma tissues. CCK-8, colony formation, and EdU were used to measure the cell proliferation after GRWD1 knockdown and overexpression. The distribution of the cell cycle was analyzed by flow cytometry. The effect of GRWD1 knockdown on migration and invasion was analyzed by wound healing and transwell assays. RESULTS: Overexpression of GRWD1 in colon carcinoma tissues was associated with pathological grading, tumor size, N stage, TNM stage, and poor survival. GRWD1 had high sensitivity and specificity in distinguishing colon cancer from noncancerous tissues, and might be served as an independent prognosis in colon carcinoma patients. Knockdown of GRWD1 significantly inhibited the cell proliferation and colony formation, and induced cell cycle arrest and more drug susceptibility, and suppressed the migration and invasion. GRWD1 exhibited these oncogenic activities might be associated with its regulation on the expression of PCNA and Ki67, Cyclin A2 and Cyclin B1, ABCC1 and GSTP1, MTA1 and MTA2. CONCLUSION: GRWD1 may play an oncogenic activity in the development of colon carcinoma and its overexpression was associated with malignant characteristics and poor survival outcome of colon carcinoma. GRWD1 might be a potential target for future therapy.
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Ferroptosis is a form of iron-dependent programmed cell death. Regulation of ferroptosis in tumor cells is a novel treatment modality. The present study aimed to investigate ferroptosis-related long non-coding RNAs (lncRNAs) and construct a prognostic model for colon adenocarcinoma (COAD). RNA- sequencing data and ferroptosis-related genes were obtained from The Cancer Genome Atlas database and FerrDb database. COAD patients were randomly assigned to training- and validation groups. The Least Absolute Shrinkage and Selection Operator regression and Cox regression model were used to determine and develop a predictive model. The model was corroborated using the validation group and the entire group. In total, 259 ferroptosis-related genes and 905 ferroptosis-related LncRNAs were obtained. Cox model revealed and constructed seven ferroptosis-related LncRNAs signature (LINC01503, AC004687.1, AC010973.2, AP001189.3, ARRDC1-AS1, OIP5-AS1, and NCK1-DT). Patients were assigned into two groups according to the median risk score. Kaplan-Meier survival curves showed that overall survival between high- and low-risk groups was statistically significant (P<0.01). Cox multivariate analysis seven ferroptosis-related LncRNAs signature was an independent risk factor for COAD outcomes (P<0.05). The relationship between seven ferroptosis-related LncRNAs and clinicopathological features was also examined. The principal component analysis showed a difference between high- and low-risk groups intuitively. With the aid of gene set enrichment analysis, the underlying mechanisms of seven ferroptosis-related LncRNAs were uncovered, including the MAPK signaling pathway, mTOR signaling pathway, and glutathione metabolism pathway. Finally, we established and validated seven ferroptosis-related lncRNAs signature for COAD patients to predict survival. These results may provide meaningful targets for future study.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/genética , Ferroptose , RNA Longo não Codificante/genética , Idoso , Biomarcadores Tumorais/análise , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genes Neoplásicos , Genoma Humano , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Prognóstico , Modelos de Riscos Proporcionais , Risco , Medição de Risco , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Resultado do TratamentoRESUMO
OBJECTIVE: To study the risk factors associated with lymphatic metastasis of T2 rectal carcinoma. METHODS: A consecutive series of 122 patients with T2 rectal cancer who underwent radical surgery in the First Affiliated Hospital of Fujian Medical University from 2006 to 2011 were included for retrospective analysis. Risk factors associated with lymphatic metastasis were investigated. RESULTS: The rate of lymph node metastasis was 21.3% (26/122). Distance to anal verge(P<0.05), morphological type(P<0.05), histological type(P<0.05), tumor differentiation(P<0.05), and depth of invasion(P<0.05) were risk factors for lymph node metastasis in T2 rectal cancer by univariate analysis. The depth of invasion remained statistically significant by multivariate analysis. The rate of lymph node metastasis was 13%(7/54) in patients with shallow muscularis propria involvement, and 28%(19/68) in those with deep muscularis involvement. CONCLUSION: For T2 rectal cancer with shallow muscularis involvement, the risk of lymph node metastasis is low and transanal excision should be considered.