Objective:To study the relationshop between cell adhesion molecules CD 62 P expression and biological behavior of rectal cancer.Methods:The levels of CD 62 P expression was observed in 40 cases of rectal cancer using SP immunohistochemistry staining.Rusults:The rate of CD 62 P expression was 65%(26/40) in rectal cancer.CD 62 P expression was more intensive in rectal cancer with infiltrated serosa and lymph node metastasis ( P 0.01).Conclusion:CD 62 P expression was correlate with infiltrated lymph node metastasis behavior of rectal cancer.The examination of Cd 62 P expression in rectal cancer may have an important value in evaluating infiltrated lymph node metastasis intensity and stage of rectal cancer.
The mitochondria are defined by their unique structure and cellular functions which includes energy production, metabolic regulation, apoptosis, calcium homeostasis, cell proliferation, cell motility and transport as well as free radical generation. Recent advances geared towards enhancing the diagnostic and prognostic value of cancer patients have targeted the circulating mitochondria genome due to its specific and unique characteristics. Circulating mitochondria DNA is known to possess short length, relatively simple molecular structure and a high copy number. These coupled with its ability to serve as a liquid biopsy makes it an easily accessible non-invasive biomarker for diagnostics and prognostics of various forms of solid tumors. In this article, we review recent findings on circulating mitochondria DNA content in cancer. In addition, we provide an insight into the potential of circulating mitochondria DNA to act as a non-invasive diagnostic biomarker and its linearity with clinical and sociodemographic characteristics.
The epigenetic silencing of tumor suppressor genes by promoter methylation plays an increasingly important role in cancer research. A number of studies have reported the contribution of HIC1 promoter methylation towards the occurrence and development of solid tumors, even though HIC1 promoter methylation has also been found in normal and benign tissue samples. We sought to perform a more accurate and comprehensive meta-analysis to assess the association between HIC1 promoter methylation and cancer risk. We searched and retrieved all published studies on HIC1 promoter methylation in PubMed, Google Scholar, Embase, Cochrane Library, and Web of Science databases. After two reviewers checked the studies and extracted the necessary data independently, the meta-analysis was performed using STATA 12.0 software. A total of 14 case-control studies (949 cancer patients, 282 benign, and 371 normal controls) were included in our study. We report a significantly elevated HIC1 promoter methylation in tumor samples compared to normal (OR = 7.02, 95 % CI 3.12-15.78, P < 0.001) and benign controls (OR = 2.69, 95 % CI 1.13-6.42, P = 0.025). Subgroup analysis stratified by ethnicity showed a significantly reduced heterogeneity among North American (I2 = 0.0 %, P = 0.502) and European (I2 = 33.7 %, P = 0.183) samples. In addition, heterogeneity was significantly reduced among MSP based detection method (I2 = 36.4 %, P = 0.139) when samples were stratified based on the methylation detection methods. The overall outcome demonstrated that HIC1 promoter methylation may be involved in the occurrence and development of solid tumors and has the potential to serve as an epigenetic maker in various specific tumors.
Abstract Objective Gastric cancer (GC) is one of the most prevalent malignant tumors in Asian countries. Studies have proposed that lncRNAs can be used as diagnostic and prognostic indicators of GC due to the high specificity of lncRNAs expression involvement in GC. Recently, N6-methyladenosine (m6A) has also emerged as an important modulator of the expression of lncRNAs in GC. This study aimed at establishing a novel m6A-related lncRNAs prognostic signature that can be used to construct accurate models for predicting the prognosis of GC in the Asian population. Methods First, the levels of m6A modification and m6A methyltransferases expression in GC samples were determined using dot blot and western blot analyses. Next, we evaluated the lncRNAs expression profiles and the corresponding clinical data of 88 Asian GC patients retrieved from The Cancer Genome Atlas (TCGA) database. Differential expression of m6A-related lncRNAs between GC and normal tissues was investigated. The relationship between these target lncRNAs and potential immunotherapeutic signatures was also analyzed. Gene set enrichment analysis (GSEA) was performed to identify the malignancy-associated pathways. Univariate Cox regression, LASSO regression, and multivariate Cox regression analyses were performed to establish a novel prognostic m6A-related lncRNAs prognostic signature. Moreover, we constructed a predictive nomogram and determined the expression levels of nine m6A-related lncRNAs in 12 pairs of clinical samples. Results We found that m6A methylation levels were significantly increased in GC tumor samples compared to adjacent normal tissues, and the increase was positively correlated with tumor stage. Patients were then divided into two clusters (cluster 1 and cluster 2) based on the differential expression of the m6A-related lncRNAs. Results showed that there was a significant difference in survival probability between the two clusters ( p = 0.018). Notably, the low survival rate in cluster 2 may be associated with high expression of immune cells (resting memory CD4 + T cells, p = 0.027; regulatory T cells, p = 0.0018; monocytes, p = 0.00095; and resting dendritic cells, p = 0.015), and low expression of immune cells (resting NK cells, p = 0.033; and macrophages M1, p = 0.045). Enrichment analysis indicated that malignancy-associated biological processes were more common in the cluster 2 subgroup. Finally, the risk model comprising of six m6A-related lncRNAs was identified as an independent predictor of prognoses, which could divide patients into high- or low-risk groups. Time-dependent ROC analysis suggested that the risk score could accurately predict the prognosis of GC patients. Patients in the high-risk group had worse outcomes compared to patients in the low-risk group, and the risk score showed a positive correlation with immune cells (resting memory CD4 + T cells, R = 0.31, P = 0.038; regulatory T cells, R = 0.42, P = 0.0042; monocytes, R = 0.42, P = 0.0043). However, M1 macrophages (R = -0.37, P = 0.012) and resting NK cells (R = -0.31, P = 0.043) had a negative correlation with risk scores. Furthermore, analysis of clinical samples validated the weak positive correlation between the risk score and tumor stage. Conclusions The risk model described here, based on the six m6A-related lncRNAs signature, and may predict the clinical prognoses and immunotherapeutic response in Asian GC patients.
Cyclin-dependent kinase 1 (CDK1) regulates the cell cycle and is highly expressed in most tumors. CDK1 expression has been associated with poor disease prognosis. This study aimed to identify the prognostic value of CDK1 in pan-cancer and investigate the association between CDK1 expression and immune cell infiltration.
Gastrointestinal (GI) cancers are among the most fatal diseases in the world. Numerous studies have demonstrated the relationship between autophagy and development of gastrointestinal cancers. However, whether autophagy-related genes can predict prognosis of GI cancers in individuals of Asian ancestry has not been defined. This study, evaluated the prognostic value of autophagy-related genes in gastrointestinal cancer. Expression profile of autophagy-related genes for 296 gastrointestinal cancer patients of Asian ancestry was downloaded from the TCGA database (TCGA-LIHC, TCGA-STAD, TCGA-ESCA, TCGA-PAAD, TCGA-COAD, TCGA-CHOL, and TCGA-READ). The prognostic value of the autophagy-related genes was evaluated using univariate Cox, LASSO, and multivariate Cox regression analyses. The risk score of the autophagy-related gene signature was calculated to assess its predictive prognostic value for GI cancers. Forty-seven differentially expressed autophagy-related genes, in Asian patients with gastrointestinal cancers, were identified. Of the 47 genes, 4 were associated with prognosis of GI cancer (SQSTM1, BIRC5, NRG3, and CXCR4). A prognostic model for GI cancer, based on the expression of the above 4 genes in the training set, showed that cancer patients were stratified into high-risk and low-risk groups (P < 0.05). The utility of the model for overall survival (OS) of GI cancer patients was consistent across the entire set, training set, and test set (entire set: P = 4.568 × 10-4; train set: P = 5.718 × 10-3; test set: P = 3.516 × 10-2). The sensitivity and specificity of the ROC curve of the above prognostic model in predicting the 5-year prognosis of GI cancer was satisfactory (entire set: 0.728; train set: 0.727; test set: 0.733). Analysis of clinical samples validated the overexpression of the 4 genes (SQSTM1, BIRC5, NRG3, and CXCR4) in tumor tissues relative to paired normal tissues, consistent with bioinformatic findings. Expression of the 4 autophagy-related genes (SQSTM1, BIRC5, NRG3, and CXCR4) can accurately predict the prognosis of gastrointestinal tumors in Asian patients.
We previously revealed that increased phosphorylation of TOB1, a tumor suppressor protein, may promote the progression of gastric cancer. However, the phosphorylated sites on TOB1 and their functional implication in gastric cancer remain to be clarified. Here, we addressed these questions using the gastric mucosal epithelial cell line GES-1 and three gastric cancer cell lines (HGC-27, AGS, and MKN-1). Compared with the control GES-1 cells, the gastric cancer cells showed decreased levels of TOB1 protein and increased levels of phosphorylated TOB1 (p-TOB1) by Western blotting. Then, TOB1 protein was enriched and purified by immunoprecipitation. Two novel phosphorylation sites at threonine 172 (T172) and serine 320 (S320) in TOB1 were identified in gastric cancer MKN-1 cells using LC-MS/MS. Furthermore, treatment with the serine/threonine kinase inhibitor staurosporine (STS; 2 nmol/L, 8 h) significantly decreased the levels of p-TOB1. As a result, the proliferation, migration, and invasion of gastric cancer cells were diminished, accompanied by an increased proportion of cells in G1 phase and a decreased proportion of cells in G2 phase. Taken together, these findings indicate for the first time that TOB1 is phosphorylated at T172 and S320 in gastric cancer cells, which are sensitive to STS. Downregulation of p-TOB1 levels by STS treatment can weaken the malignant phenotype of gastric cancer cells and block their progression through the cell cycle. Moreover, STS may exert its antiproliferative activity in gastric cancers by restoring TOB1 protein activity.
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