RESUMO
BACKGROUND: The aim of this study was to investigate the differences in oncological outcome and inflammatory biomarkers between right-sided colon cancer (RCC) and left-sided colorectal cancer (LCRC). METHODS: We retrospectively analyzed 339 patients with stage I-III colorectal cancer, including 125 RCC patients and 214 LCRC patients, who underwent radical resection from January 2012 to January 2014. Comparison of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) between RCC and LCRC was evaluated using the Mann-Whitney U test. Overall survival (OS) and disease-free survival (DFS) were analyzed using Kaplan-Meier analysis and compared using the log-rank test. Univariate and multivariate Cox regression analyses were used to identify the prognostic value of inflammatory markers. RESULTS: Patients with RCC had higher NLR (P = .002) and PLR (P < .001) but lower LMR (P = .002) compared to LCRC. In stage I-III, RCC showed poorer OS and DFS than LCRC (61.6% vs 71.5%, P = .018; 64.8% vs 76.2%, P = .006). Univariate and multivariate analyses indicated that NLR, PLR, and LMR were independent predictors for both OS and DFS in RCC, whereas only PLR was found to be an independent prognostic predictor in LCRC. CONCLUSION: The prognosis and prognostic value of inflammatory biomarkers were significantly different between RCC and LCRC. Novel therapeutic strategies are needed, and proper prognostic predictors should be selected according to colorectal tumor location.
Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Inflamação/patologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Resultado do TratamentoRESUMO
BACKGROUND: Inhibin subunit beta B (INHBB) is a protein-coding gene that participated in the synthesis of the transforming growth factor-ß (TGF-ß) family members. The study is aimed at exploring the clinical significance of INHBB in patients with colorectal cancer (CRC) by bioinformatics analysis. METHODS: Real-time PCR and analyses of Oncomine, Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) databases were utilized to evaluate the INHBB gene transcription level of colorectal cancer (CRC) tissue. We evaluated the INHBB methylation level and the relationship between expression and methylation levels of CpG islands in CRC tissue. The corresponding clinical data were obtained to further explore the association of INHBB with clinical and survival features. In addition, Gene Set Enrichment Analysis (GSEA) was performed to explore the gene ontology and signaling pathways of INHBB involved. RESULTS: INHBB expression was elevated in CRC tissue. Although the promoter of INHBB was hypermethylated in CRC, methylation did not ultimately correlate with the expression of INHBB. Overexpression of INHBB was significantly and positively associated with invasion depth, distant metastasis, and TNM stage. Cox regression analyses and Kaplan-Meier survival analysis indicated that high expression of INHBB was correlated with worse overall survival (OS) and disease-free survival (DFS). GSEA showed that INHBB was closely correlated with 5 cancer-promoting signaling pathways including the Hedgehog signaling pathway, ECM receptor interaction, TGF-ß signaling pathway, focal adhesion, and pathway in cancer. INHBB expression significantly promoted macrophage infiltration and inhibited memory T cell, mast cell, and dendritic cell infiltration. INHBB expression was positively correlated with stromal and immune scores of CRC samples. CONCLUSION: INHBB might be a potential prognostic biomarker and a novel therapeutic target for CRC.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Subunidades beta de Inibinas/genética , Idoso , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Ilhas de CpG , Metilação de DNA , Feminino , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Proteínas Hedgehog/genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Prognóstico , Regiões Promotoras Genéticas , Modelos de Riscos Proporcionais , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Fator de Crescimento Transformador beta/genéticaRESUMO
The aberrant expression of microRNA (miRNAor miR)3835p has been found in numerous types of cancer. However, the function of miR3835p in gastric cancer (GC) remains elusive and requires further investigation. In the present study, the level of miR3835p and cancerous inhibitor of PP2A (CIP2A) in GC cell lines was determined by reverse transcriptionquantitative PCR analysis. GC cell proliferation, apoptosis and cell cycle distribution were determined by the MTT assay and flow cytometry, respectively. The mRNA target of miR3835p was identified by dual luciferase activity assay. It was observed that the expression of miR3835p was lower and that of CIP2A was higher in GC cells compared with the GES1 normal human gastric epithelial cell line. Transfectoin with miR3835p mimic significantly inhibited GC cell proliferation, while it promoted cell apoptosis and G0/G1 arrest by targeting CIP2A. Taken together, the findings of the present study demonstrate that miR3835p inhibits GC cell proliferation and promotes apoptosis and G0/G1 arrest by targeting CIP2A, indicating that targeting miR3835p may hold promise as a future therapeutic strategy for patients with GC.