scholarly journals Cancer Stem Cell Marker DCLK1 Correlates with Tumorigenic Immune Infiltrates in the Colon and Gastric Adenocarcinoma Microenvironments

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 274 ◽  
Author(s):  
Xiangyan Wu ◽  
Dongfeng Qu ◽  
Nathaniel Weygant ◽  
Jun Peng ◽  
Courtney W. Houchen

Immunotherapy that has proven efficacy in several solid cancers plays a partial role in improving clinical outcomes of advanced gastrointestinal (GI) cancers. There is an unmet need to find new immune-related therapeutic targets. Doublecortin-like kinase 1 (DCLK1) marks tuft cells which are recognized as cancer-initiating cells and regulators of the type II immune response, and has been studied for its role in many cancers including colon and gastric cancers, but its role in tumor immunity remains unexplored. In the current study, we analyzed colon and gastric cancer RNA sequencing data from 283 and 415 patients, respectively, from The Cancer Genome Atlas (TCGA). High DCLK1 expression predicted the worse clinical outcomes in colon and gastric cancer patients and correlated with increased immune and stromal components. Further analysis indicated that DCLK1 was strongly linked to infiltration of multiple immune cell types, especially TAMs and Treg, and strongly correlated with increased CD8+ T cell inhibitors TGFB1 and CXCL12 and their receptors, suggesting it may contribute to TAM-mediated inhibition of CD8+ T cells. Interestingly, we found that DCLK1 was a prognostic biomarker in left-sided colon cancer, which has worse outcomes and demonstrates a reduced response to existing immunotherapies. In conclusion, our results demonstrate that DCLK1 is linked with functional regulation of the tumor microenvironment and may have potential as a prognostic biomarker and adjuvant target to promote immunotherapy sensitivity in colon and gastric cancer patients.

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Jun Li ◽  
Qingfeng Xu ◽  
Wen Wang ◽  
Shaojun Sun

Abstract The MIR100HG expression was observed to be up-regulated or down-regulated in human cancer tissues depending on tumor types. However, there was no report about the role of MIR100HG in gastric cancer. In our study, we first found levels of MIR100HG expression were increased in gastric cancer cell lines and tissue samples compared with normal gastric epithelial cell line and adjacent normal gastric mucosa tissue samples, respectively. Moreover, high MIR100HG expression was positively associated with clinical stage, tumor invasion, lymph node metastasis, and distant metastasis in gastric cancer patients. Survival analysis showed MIR100HG expression was negative correlated with clinical outcome in gastric cancer patients from The Cancer Genome Atlas (TCGA) database or our study, and high MIR100HG expression served as an independent poor prognostic factor for gastric cancer patient’s overall survival. The study in vitro suggested down-regulation of MIR100HG expression inhibits cell proliferation, migration, and invasion in gastric cancer. In conclusion, MIR100HG is a credible prognostic biomarker and functions as an oncogenic lncRNA in gastric cancer.


2021 ◽  
pp. 153568
Author(s):  
Mingxia Jiang ◽  
Ling Qi ◽  
Kexin Jin ◽  
Lisha Li ◽  
Yiming Wu ◽  
...  

2021 ◽  
Author(s):  
Yanling Ma ◽  
WenBo Qi ◽  
BaoHong Gu ◽  
XueMei Li ◽  
ZhenYu Yin ◽  
...  

Abstract Objective: To investigate the association between ILDR1 and prognosis and immune infiltration in gastric cancer. Methods: We analyzed the RNA sequencing data of 9736 tumor tissues and 8587 normal tissues in the TCGA and GTEx databases through the GEPIA2 platform. The expression of ILDR1 in gastric cancer and normal gastric mucosa tissues with GEPIA and TIMER. Clinical subgroup analysis was made through Kaplan-Meier analysis. Analyzed the correlation between ILDR1 and VEGFA expression in gastric cancer, through the gene sequencing data of gastric cancer in TCGA. Explored the relationship between ILDR1 methylation and the prognosis of gastric cancer patients through the MethSurv database. The correlation between ILDR1 and immune cells and the correlation of copy number variation were explored through the TIMER database. Results: ILDR1-high GC patients had a lower PFS and OS. High ILDR1 expression was significantly correlated with tumor grade. There was a negative correlation between the ILDR1 expression and the abundances of CD8+ T, Macrophages and DC and etc. The methylation level of ILDR1 is associated with a good prognosis of gastric cancer. ILDR1 copy number variation was correlated with immune cells, IDLR1 arm-loss was associated with the infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells, and arm-duplication was associated with the infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells. Conclusion: The increased expression of ILDR1 is associated with poor prognosis in patients with gastric cancer. ILDR1 can be used as a novel predictive biomarker to provide a new therapeutic target for gastric cancer patients.


2021 ◽  
Vol 10 (1) ◽  
pp. 1915560
Author(s):  
Kaifeng Jin ◽  
Yifan Cao ◽  
Yun Gu ◽  
Hanji Fang ◽  
Yuchao Fei ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Taweesak Tongtawee ◽  
Wareeporn Wattanawongdon ◽  
Theeraya Simawaranon ◽  
Soraya Kaewpitoon ◽  
Sivamate Kaengpenkae ◽  
...  

Here we investigated CD44 protein expression and its polymorphisms in patients with chronic gastritis, precancerous gastric lesions, and gastric cancer; and we evaluated our result with the risk of CD44 protein expression and clinicopathological characteristics. Our results obtained by analyzing 162 gastric cancer patients, 125 chronic gastritis, and 165 precancerous gastric lesions from three study centers in Thailand showed that CD44 expression was significantly higher in patients with precancerous gastric lesions and gastric cancer while patients with chronic gastritis were negative for CD44 staining (p=0.036). We further observed the significant association of variant genotype; gastric cancer patients carrying AG or GG of CD44 rs187116 had more increased risk of CD44 expression than wild-type (WT) carriers (AG: odds ratio (OR) = 5.67; 95% CI = 1.57–7.23; p=0.024 and GG: OR = 8.32; 95% CI = 2.94–11.42; p=0.016), but no significant difference in the risk of CD44 expression due to polymorphism in patients with precancerous gastric lesions. Our results suggested that CD44 expression could be used as a marker for the prediction of gastric cancer development, particularly in patients with precancerous gastric lesions carrying AG or GG, who were selected to surveillance follow-up for gastric cancer prevention.


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