scholarly journals Dysregulation of CCL18/CCR8 axis predicts poor prognosis in patients with gastric cancer

2018 ◽  
Vol 16 ◽  
pp. 205873921879688
Author(s):  
Jie Yi ◽  
Shao-Jie Jiang

Increasing data have shown that the dysregulation of C-C motif chemokine ligand 18 (CCL18) and C-C motif chemokine receptor (CCR8) is involved in the development and progression of multiple malignancies. However, the clinical significance of CCL18/CCR8 axis in gastric cancer (GC) was still undocumented. In this study, the expression levels of CCL18 and its receptor CCR8 and their correlation with the clinicopathological characteristics and prognosis in patients with GC were analyzed by TCGA RNA sequencing data. Cox proportional hazard regression model was performed to assess the association between CCL18/CCR8 expression and overall survival (OS) and tumor recurrence in patients with GC. As a consequence, we found that the expression of CCL18 was markedly elevated in GC samples as compared with the adjacent normal tissues and acted as an independent prognostic factor of tumor recurrence in patients with GC. Subsequently, Pearson correlation analysis revealed that CCL18 possessed a positive correlation with CCR8 expression in GC samples. CCR8 expression was upregulated in GC tissues and exhibited the association with poor survival in patients with GC. Taken together, our findings demonstrated that the dysregulation of CCL18/CCR8 axis could predict the poor prognosis in patients with GC and provide a potential antitumor target for the treatment of GC.

2018 ◽  
Vol 32 ◽  
pp. 205873841879031 ◽  
Author(s):  
Xiao-Yu Chen ◽  
Jing Zhang ◽  
Li-Dan Hou ◽  
Rui Zhang ◽  
Wei Chen ◽  
...  

Targeting of the programmed cell-death 1 ligand 1 (PD-L1) signal pathway is a promising treatment strategy in several cancers. The purpose of this study was to evaluate the clinical significance of PD-L1 in patients with colon adenocarcinoma (COAD). A total of 240 patients who were diagnosed with COAD from The Cancer Genome Atlas (TCGA) RNA-sequencing data and another cohort for pair-matched COAD samples (n = 40) in tissue microarray (TMA) were enrolled in this study. The correlation of PD-L1 or miR-191-5p expression with clinicopathological features and prognosis in patients with COAD was further analyzed using TCGA data and TMA. The Cox proportional hazard regression model was used to evaluate the association of PD-L1 or miR-191-5p expression with overall survival (OS) and tumor recurrence in patients with COAD. The microRNAs (miRNAs) that target PD-L1 gene were identified by bioinformatics and Spearman correlation analysis. We found that PD-L1 expression was increased in COAD tissues and was correlated with poor survival and tumor recurrence in patients with COAD. The increased expression of PD-L1 was attributed to the dysregulation of miR-191-5p expression rather than its genetic or epigenetic alterations. Moreover, the expression of miR-191-5p presented the negative correlation with PD-L1 expression and acted as an independent prognostic factor of OS in patients with COAD. Therefore, PD-L1 may predict poor prognosis and is negatively associated with miR-191-5p expression in patients with COAD.


2018 ◽  
Vol 16 ◽  
pp. 205873921881969
Author(s):  
Yang Teng ◽  
Rong Tang ◽  
Shao-Jie Jiang

Our present study aimed to reveal the clinical significance of miR-605-5p/STAT2 axis in patients with gastric cancer (GC). The association of STAT2 or miR-605-5p expression with the clinicopathological characteristics and prognosis in patients with GC was analyzed using the tissue microarray and TCGA RNA-seq data. Pearson correlation analysis was used to evaluate the correlation of STAT2 with miRNAs expression in GC tissues. Cox proportional hazard regression model was conducted to assess whether STAT2 or miR-605-5p expressions was an independent prognostic factor in patients with GC. Consequently, we found that STAT2 expression levels were dramatically elevated in GC tissues and acted as an independent prognostic factor of poor survival in patients with GC. The upregulation of STAT2 was attributable to the dysregulation of miR-605-5p rather than its genetic and epigenetic modulation. MiR-605-5p indicated a negative correlation with STAT2 expression and was an independent prognostic factor of poor survival in patients with GC. In conclusion, dysregulation of miR-605-5p/STAT2 axis predicted a poor survival in patients with GC.


2021 ◽  
Vol 8 ◽  
Author(s):  
Cheng Chen ◽  
Xinjie Jiang ◽  
Fei Xia ◽  
Xudong Chen ◽  
Weiguo Wang

Background: Primary renal leiomyosarcoma (LMS) is an exceedingly rare entity with a poor prognosis. We summarized the clinicopathological characteristics, treatment choice, and survival outcomes of LMS from the Surveillance, Epidemiology, and End Results (SEER) database.Methods: Renal LMS and kidney renal clear cell carcinoma (KIRC) data from 1998 to 2016 were collected from the SEER database. The continuous variables were analyzed using t-tests, while the categorical variables were analyzed using Pearson's chi-squared or Fisher's exact tests. Propensity score matching (PSM) was also performed. The cancer-specific survival (CSS) and overall survival (OS) curves were estimated using Kaplan-Meier analyses and compared by log-rank tests. The risk factors for CSS and OS were estimated using univariable and multivariable Cox proportional hazard regression models.Results: A total of 140 patients with renal LMS and 75,401 patients with KIRC were enrolled. These groups differed significantly in sex, race, tumor size, grade, SEER stage, surgery, radiation, and chemotherapy. Renal LMS exhibited poorer CSS and OS compared with KIRC before and after PSM. For renal LMS, the univariate Cox proportional hazard regression model indicated that larger tumor size, higher tumor grade, higher SEER stage, and chemotherapy were risk factors for CSS and OS, while surgery appeared to be a protective factor. However, only tumor grade, SEER stage, and receiving surgery remained independent prognostic factors in the multivariable Cox proportional hazard regression model. In addition, subgroup analyses indicated that surgery remained a protective factor for advanced renal LMS. However, there was no survival benefit for patients receiving chemotherapy.Conclusions: Primary renal LMS is an exceedingly rare entity with distinct clinicopathological features and a poor prognosis. A higher tumor grade and late stage may indicate a poor prognosis. Complete tumor resection remains to be the first treatment choice, while chemotherapy may be a palliative treatment for patients with advanced disease.


2021 ◽  
Vol 20 ◽  
pp. 153303382110049
Author(s):  
Tao Ran ◽  
ZhiJi Chen ◽  
LiWen Zhao ◽  
Wei Ran ◽  
JinYu Fan ◽  
...  

Background and Objective: Gastric cancer (GC) is a common tumor malignancy with high incidence and poor prognosis. Laminin is an indispensable component of basement membrane and extracellular matrix, which is responsible for bridging the internal and external environment of cells and transmitting signals. This study mainly explored the association of the LAMB1 expression with clinicopathological characteristics and prognosis in gastric cancer. Methods: The expression data and clinical information of gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG). And we analyzed the relationship between LAMB1 expression and clinical characteristics through R. CIBERSORTx was used to calculate the absolute score of immune cells in gastric tumor tissues. Then COX proportional hazard models and Kaplan-Meier curves were performed to evaluate the role of LAMB1 and its influence on prognosis in gastric cancer patients. Finally, GO and KEGG analysis were applied for LAMB1-related genes in gastric cancer, and PPI network was constructed in Cytoscape software. Results: In the TCGA cohort, patients with gastric cancer frequently generated LAMB1 gene copy number variation, but had little effect on mRNA expression. Both in the TCGA and ACRG cohorts, the mRNA expression of LAMB1 in gastric cancer tissues was higher than it in normal tissues. All patients were divided into high expression group and low expression group according to the median expression level of LAMB1. The elevated expression group obviously had more advanced cases and higher infiltration levels of M2 macrophages. COX proportional hazard models and Kaplan-Meier curves revealed that patients with enhanced expression of LAMB1 have a worse prognosis. GO/KEGG analysis showed that LAMB1-related genes were enriched in PI3K-Akt signaling pathway, focal adhesion, ECM-receptor interaction, etc. Conclusions: The high expression of LAMB1 in gastric cancer is related to the poor prognosis of patients, and it may be related to microenvironmental changes in tumors.


2020 ◽  
Vol 19 ◽  
pp. 153303381990112
Author(s):  
Kan-kan Yang ◽  
Hui-mian Xu ◽  
Jin-yu Huang ◽  
Yu-xuan Guo ◽  
Zhen-ning Wang

Background: SRY-related HMG box-12, which is associated with the prognosis of cancer, has been frequently described. However, both SRY-related HMG box-12 expression and its relationship with clinicopathological variables and patient survival have not been defined in gastric cancer. The aim of our study was to examine the prognostic value of SRY-related HMG box-12 expression in patients with gastric cancer. Methods: In this study, we determined SRY-related HMG box-12 expression in 79 primary gastric cancer tissues and 79 matched adjacent nontumor tissues by immunohistochemistry and then calculated the survival rate using the Kaplan-Meier method. Cox proportional hazard regression model was used to analyze predictors of gastric cancer. Western blot and quantitative real-time polymerase chain reaction were used to investigate the difference in SRY-related HMG box-12 expression between normal gastric epithelial cells and gastric cancer cells at the protein level and RNA level, respectively. Results: SRY-related HMG box-12 was downregulated in gastric cancer tissues. Low SRY-related HMG box-12 expression was significantly associated not only with lymph node metastasis ( P = .027) and TNM stage ( P = .021) but also with disease-specific survival in patients with gastric cancer. Multivariate analysis demonstrated TNM stage was an independent factor predicting poor survival ( P = .034). Conclusions: Low SRY-related HMG box-12 expression is associated with poor clinical outcomes in gastric cancer.


2021 ◽  
Author(s):  
Jun Du ◽  
Mengxiang Zhu ◽  
Wenwu Yan ◽  
Changsheng Yao ◽  
Qingyi Li ◽  
...  

Abstract Background The molecular role of carboxypeptidase X, M14 family member (CPXM1) in oncogenesis or tumor progression remains unclear. The aim of this study was to determine whether CPXM1 can be used as a potential prognostic biomarker for gastric cancer (GC). Methods We first demonstrated the relationship between CPXM1 expression and GC in various public databases. Secondly, the expression of CPXM1 in GC tissues was further verified by immunohistochemical staining using tissue microarray containing 96 cases of GC patients. Kaplan–Meier analysis and a Cox proportional hazard regression model were performed to evaluate the relationship between the expression of CPXM1 and the survival of GC patients. Finally, we used the expression data of CPXM1 in The Cancer Genome Atlas database to predict CPXM1-related signaling pathways through bioinformatics analysis. Results The expression level of CPXM1 in GC tissues was significantly correlated with tumor size (p = 0.041) and lymph node metastasis (p = 0.014). In addition, Kaplan–Meier analysis showed that the expression of CPXM1 in GC tissues was significantly associated with poor prognosis (p = 0.011). Multivariate analysis indicated that CPXM1 is a potential predictor of poor prognosis in GC patients (p = 0.026). The results of biosynthesis analysis demonstrated that the data set of CPXM1 high expression was mainly enriched in cancer-related signal pathways. Conclusion CPXM1 is an effective biomarker for the prognosis of GC patients and may play a key role in the occurrence and progression of GC.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9536
Author(s):  
Xin Li ◽  
Ling Chen ◽  
Chuan Gu ◽  
Qiaoli Sun ◽  
Jia Li

Background The CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) is a key regulator of the programed death receptor ligand-1 (PD-L1) protein. However, the usefulness of CMTM6 expression as a prognostic indicator and the relationship between CMTM6 and PD-L1 expression in gastric cancer (GC) remains unclear. Objectives We evaluated the expression and prognostic implications of CMTM6 in GC tissue and its relationship with PD-L1 expression. Patients and methods The protein expressions of CMTM6 and PD-L1 were detected in 122 cases of postoperative GC tissue using immunohistochemical (IHC) assays. Kaplan–Meier survival analysis was used to calculate the survival probability and a log-rank test was used to compare the survival curves. Univariate and multivariate Cox proportional hazard regression analyses were used to evaluate the clinically-related factors associated with survival. Pearson’s correlation was used to determine the correlation analysis and estimate the statistical significance. The univariate and multivariate logistic regression analyses were used to analyze the relationship between clinically-related factors and PD-L1 expression. Results Kaplan–Meier survival analysis showed that patients with high CMTM6 expression had shorter overall survival (OS) than those with low expression (P < 0.001). The expression of CMTM6 was an independent risk factor for prognosis in multivariate Cox proportional hazard regression analyses (HR:2.221, CI% [1.36–3.628], P = 0.001). The OS of patients with positively expressed PD-L1 was significantly shorter than those with negatively expressed PD-L1 (P = 0.003). The expression of CMTM6 was significantly related to the positive expression of PD-L1 in gastric cancer tissues (r = 0.186, P = 0.041). The expression of CMTM6 was the independent risk factor for PD-L1 expression in multivariate logistic regression analysis (OR:2.538, CI% [1.128–5.714], P = 0.024). Conclusion CMTM6 expression is significantly related to PD-L1 and may be a useful prognostic indicator and a specific therapeutic target for cancer immunotherapy for GC patients.


2021 ◽  
Author(s):  
Huining Fan ◽  
Xiang-Yun Zhao ◽  
Rui Liang ◽  
Xiao-Yu Chen ◽  
Jing Zhang ◽  
...  

Abstract Background: CircRNAs are a new subset of noncoding RNAs formed by covalent closed loops and play crucial roles in the regulation of cancer gene expression. However, the roles and underlying mechanisms of circRNAs in gastric cancer (GC) remain indistinct. This study aimed to explore the role and mechanism of hsa_circ_0006421 (circPTK2) in GC.Methods: The differential expression of circRNAs between GC tissues and adjacent normal tissues were identified by a circRNA expression profiling. Associations of circPTK2 or miR-134-5p expression with clinicopathological characteristics and prognosis of GC patients were analyzed by chi-square of Fisher’s exact tests and Kaplan-Meier analysis. CCK8, colony formation, EdU assays and animal models were performed to assess the effects of circPTK2 on proliferation and invasion of GC cells. CircPTK2-specific probes were used to purify the RNA pulled down from the circPTK2, and enrichment of circPTK2 and miR-134-5p was detected by qRT-PCR. The effects of circPTK2 on miR-134-5p expression and CELF2/PTEN signaling were examined by qRT-PCR and Western blotting analysis. Results: Low expression of circPTK2 and high expression of miR-134-5p were related to the poor survival, and high expression of miR-134-5p was related to the tumor recurrence in GC patients. Overexpressing circPTK2 suppressed the proliferation, colony formation, DNA synthesis and cell invasion as well as xenograft tumor growth and lung metastasis in vitro and in vivo, whereas silencing circPTK2 had the opposite effects. Moreover, circPTK2 was negatively correlated and co-localized with miR-134-5p in the cytoplasm of GC tissue cells. circPTK2 bound to and sponged miR-134-5p in GC cells, and miR-134-5p facilitated cell growth and invasion but attenuated circPTK2 induced tumor suppressive effects and CELF2/PTEN signaling activation in GC cells. Conclusions: circPTK2 functions as a tumor suppressor in GC by sponging miR-134-5p and activating the CELF2/PTEN axis.


2021 ◽  
Vol 43 (3) ◽  
pp. 1529-1547
Author(s):  
Lixiong Peng ◽  
Jiang Chang ◽  
Xilin Liu ◽  
Shiying Lu ◽  
Honglin Ren ◽  
...  

Melanocortin 1 receptor (MC1R) is thought to be a marker of poor prognosis and a potential target for the treatment of melanoma. Studies have found that MC1R promotes several tumor behaviors, including cell proliferation and differentiation, pigment formation, and genome damage repair. Some single-nucleotide polymorphisms (SNPs) of MC1R are involved in the occurrence and development of melanoma. A few studies have reported a relationship between MC1R and colorectal cancer (CRC). In this research, our objective was to examine MC1R expression and MC1R SNPs and investigate their correlation with the clinicopathological features of human CRC tissues. We evaluated MC1R mRNA expression by performing bioinformatic analyses on human CRC expression datasets. We used Western blotting and RT-qPCR to compare MC1R expression in CRC tissues with that in normal tissues, and MC1R SNPs in CRC tissues were detected by PCR-direct sequencing (DS). The expression of MC1R was significantly decreased in CRC tissues compared with normal tissue, and its expression was negatively associated with P53 expression, MLH1 expression, and PMS2 expression, and high MC1R expression was significantly associated with microsatellite instability (MSI). MC1R SNPs were also associated with the clinicopathological characteristics of CRC; for example, the rs2228479 locus genotype was correlated with Ki67 status, and the rs885479 locus genotype was correlated with age and T stage. In conclusion, MC1R plays a crucial role in the progression of CRC and may be a marker of poor prognosis in CRC.


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