Protein regulator of cytokinesis-1 expression: prognostic value in lung squamous cell carcinoma patients.
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ABSTRACT:
SUBMITTER: Zhan P
PROVIDER: S-EPMC5542988 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
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Project description:Survivin, a new member of the family of apoptosis inhibitors, is expressed almost exclusively in proliferating cells, above all in cancers. Subcellular localisation and prognostic implications of the survivin protein have not yet been determined in oesophageal squamous cell carcinoma. The survival of 84 patients with oesophageal squamous cell carcinomas was correlated with the extent of immunohistochemical survivin expression in tumour cell nuclei. Tumours were scored positive when >5% cells stained positive. Patients were followed up for at least 5 years or until death. In normal oesophageal squamous cell epithelium, some cytoplasmic survivin expression was detected in the basal cells, whereas proliferating cells showed nuclear staining of survivin. Nuclear expression of survivin was also detected in 67 cancers (80%). The mean survival for patients of this group (28 months, range 20-36) was significantly less than that for patients without survivin expression in the tumour cell nuclei (108 months, range 62-154, P=0.003). Using univariate analysis, nuclear survivin expression (P=0.003), tumour depth (P=0.001), lymph node metastasis (P=0.003) and stage (P<0.001) were the best predictors of survival. In contrast, cytoplasmic survivin staining was noted in 53 (63%) tumours and had no prognostic relevance. In conclusion, the analysis of nuclear survivin expression identifies subgroups in oesophageal squamous cell cancer with favourable (survivin(-)) or with poor prognosis (survivin(+)). We suggest that the determination of nuclear survivin expression could be used to individualise therapeutic strategies in oesophageal squamous cell cancer in the future.
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Project description:Human leukocyte antigen (HLA) class Ⅰ molecules play a central role in anticancer immunity, but their prognostic value in oral squamous cell carcinoma (OSCC) remains unclear. We examined HLA class I expression in 2 distinct tumor compartments, namely, the tumor center and invasive front, and evaluated the association between its expression pattern and histopathological status in 137 cases with OSCC. Human leukocyte antigen class Ⅰ expression was graded semiquantitatively as high, low, and negative. At the invasive front of the tumor, HLA class I expression was high in 72 cases (52.6%), low in 44 cases (32.1%), and negative in 21 cases (15.3%). The HLA class I expression in the tumor center was high in 48 cases (35.0%), low in 58 cases (42.4%), and negative in 31 cases (22.6%). The 5-year overall survival and disease-specific survival rates were good in cases with high HLA class I expression at the invasive front; however, there was no significant difference in survival based on HLA class I expression in the tumor center. In addition, high HLA class I expression was correlated with high CD8+ T cell density, whereas negative HLA class I expression was correlated with low CD8+ T cell density at the invasive front. These results suggest that it is easier for CD8+ T cells to recognize presented peptides in the case of high HLA class Ⅰ expression at the tumor invasive front and could be a prognostic factor for OSCC.
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Project description:BackgroundAbsent in melanoma 1-like (AIM1L), also known as crystalline beta gamma domain containing 2. The relationship between AIM1L and tumors has not been fully investigated, and the biological function of AIM1L in different tumors is unknown, so we bioinformatically explored a possible relationship between AIM1L and esophageal squamous cell carcinoma (ESCC).MethodsAIM1L mRNA expression was detected by the Gene Expression Omnibus database (GSE20347, GSE161533, and GSE53625), and protein level expression was detected by immunohistochemistry. The correlation between AIM1L expression and clinical pathological characteristics was evaluated by the Wilcoxon signed rank test or chi-square test. Kaplan-Meier analysis and Cox proportional risk regression model were used to determine the prognostic value of AIM1L in ESCC patients and establish and verify a nomogram. Find genes highly related to the expression of AIM1L, conduct GO and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, and conduct GSEA analysis on the gene set. The "CIBERSORT" R package was used to explore the relationship between AIM1L and immune infiltration, and the "OncoPredict" R package was used to explore the relationship between AIM1L and drug sensitivity.ResultsCompared with the matched adjacent non-cancer tissues, the expression of AIM1L was down-regulated in ESCC tissues, and correlated with tumor grade. Kaplan-Meier survival analysis and Cox analysis showed that the low expression of AIM1L was related to the poor prognosis of ESCC patients. Enrichment analysis explained the possible function of AIM1L, GSEA determined the highly correlated signal pathway of AIM1L low expression phenotype, immune infiltration analysis determined that AIM1L was related to activated NK cells and macrophage M2, and drug sensitivity analysis determined that the low expression of AIM1L might be related to EGFR targeted drug resistance.ConclusionAIM1L may be a candidate tumor suppressor gene for ESCC and an independent molecular biomarker for the prognosis of ESCC patients.
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Project description:BACKGROUND:Tumor-infiltrating lymphocytes include tumor-reactive lymphocytes and regulatory T-cells. However, the prognostic value of tumor-infiltrating lymphocytes in oral squamous cell carcinoma (OSCC) remains unclear. METHODS:We used immunohistochemistry to evaluate the presence of tumor-infiltrating FoxP3⁺ T-cells and CTLA-4⁺ cells in four distinct histological compartments (tumor parenchyma and stroma at the tumor center, and parenchyma and stroma at the invasive front) and assessed the association between the prevalence of these cells and the histopathological status of 137 patients with OSCC. RESULTS:Five-year overall survival, disease-specific survival, and recurrence-free survival were favorable in patients with high numbers of FoxP3⁺ T-cells in the parenchyma of the invasive front. Recurrence-free survival and metastasis-free survival were decreased in patients with high numbers of CTLA-4⁺ cells in the parenchyma of the invasive front. CONCLUSIONS:The presence of FoxP3⁺ T-cells in the parenchyma of the invasive front may be a useful prognostic factor. Our results indicate that FoxP3⁺ T-cells may exert site-specific anti-tumor effects but may not play an immunosuppressive role in OSCC. In addition, our results suggest that CTLA-4+ cells suppress the function of FoxP3+ T-cells and promote anti-tumor immunity in OSCC.
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Project description:Stromal cell-derived factor-1α (SDF-1α) is a chemokine that has been reported to be involved in tumor progression in several malignancies. This study aimed to evaluate the crucial role of SDF-1α in patients with esophageal squamous cell carcinoma (ESCC) who underwent esophagectomy. A total of 169 patients with ESCC were identified, including overexpression of SDF-1α in 60 patients and low expression of SDF-1α in 109 patients by immunohistochemical analysis. Two ESCC cell lines, TE1 and KYSE30, were selected to evaluate the tumor cell proliferative effect of SDF-1α. Univariate and multivariate analyses showed that high tumor (T) status, positive lymph node metastasis, tumors located in the upper esophagus, and SDF-1α overexpression were significantly related to worse disease-free survival and overall survival. In addition, the two cell lines were treated with SDF-1α, AMD3100 (an SDF-1α-ligand receptor antagonist), and chemotherapeutic agents (cisplatin). Our in vitro study results showed that SDF-1α promoted the proliferation of tumor cells, and blocking the SDF-1α pathway displayed a growth inhibition effect in a dose-dependent manner. SDF-1α plays an important role in the progression of ESCC and is an independent prognostic factor for ESCC patients who underwent esophagectomy.
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Project description:Previous studies have demonstrated that the interleukin (IL)-6/ IL-6 receptor (IL-6R) signaling pathway contributes to the pathogenesis of lung cancer. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the two major pathological subtypes of non-small cell lung cancer (NSCLC). The present study aimed to elucidate the potential clinical prognosis and biological function of IL-6R mRNA expression in LUAD and LUSC. The search term 'lung cancer' was used to search through the Gene Expression Omnibus database. Including LUAD and LUSC datasets in The Cancer Genome Atlas database, a total of 8 LUAD and 6 LUSC datasets were included in the present analysis. It was observed that a higher expression level of IL-6R mRNA in tumor tissues was a significant positive prognostic factor for overall survival in LUAD [pooled hazard ratio (HR), 0.48 and P<0.001 for univariate analysis; pooled HR, 0.50 and P<0.001 for multivariate analysis] while there was no similar association in LUSC (pooled HR, 1.59 and P=0.062 for univariate analysis; pooled HR, 1.58 and P=0.079 for multivariate analysis). Correlation analysis revealed that IL-6 and IL-6R were negatively correlated in LUAD and positively correlated in LUSC. IL-6R and its most correlated genes were primarily involved in cell cycle progression in LUAD and primarily involved in tumor angiogenesis, invasion and metastasis in LUSC. These results suggest a possible role of tumoral expression for IL-6R in LUAD, which means it may have potential as a prognostic marker for this type of cancer.
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