Comprehensive analysis of the prognosis and immune infiltration for CXC chemokines in colorectal cancer

Yang, Xi; Wei, Yuanfeng; Feng, Si‐Shen; Xu, Yeshou; Liu, Jiao; Gao, Ling; Yang, Ju; Sun, Xinchen; Huang, Junxing; Guo, Qing

doi:10.18632/aging.203245

Cited by 19 publications

(22 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Patients with COAD also showed downregulated CXCL12/13/14 expression. The results were similar to those reported in a previous study in patients with COAD [ 30 ] and contradicted those reported previously in patients with colorectal cancer [ 29 ]. This may be due to the small sample size and the variable types of colorectal cancer.…”

Section: Discussionsupporting

confidence: 88%

“…In recent years, studies have identified VEGFA and CXC chemokines as important participants in angiogenesis, particularly tumor angiogenesis [14,15,[26][27][28]. The expression levels of CXC chemokines and VEGFA have been studied in a range of tumor types; however, findings are contradictory with regard to colonic adenocarcinomas [29,30]. This study investigated expression level, gene regulatory network, prognostic value, and target prediction of the CXC chemokine-VEGFA network for COAD from a tumor angiogenesis perspective.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Systematic Analysis of CXC Chemokine–Vascular Endothelial Growth Factor A Network in Colonic Adenocarcinoma from the Perspective of Angiogenesis

Situ

Cui

et al. 2022

BioMed Research International

View full text Add to dashboard Cite

Background. Tumor angiogenesis plays a vital role in tumorigenesis, proliferation, and metastasis. Recently, vascular endothelial growth factor A (VEGFA) and CXC chemokines have been shown to play vital roles in angiogenesis. Exploring the expression level, gene regulatory network, prognostic value, and target prediction of the CXC chemokine-VEGFA network in colon adenocarcinoma (COAD) is crucial from the perspective of tumor angiogenesis. Methods. In this study, we analyzed gene expression and regulation, prognostic value, target prediction, and immune infiltrates related to the CXC chemokine-VEGFA network in patients with COAD using multiple databases (cBioPortal, UALCAN, Human Protein Atlas, GeneMANIA, GEPIA, TIMER (version 2.0), TRRUST (version 2), LinkedOmics, and Metascape). Results. Our results showed that CXCL1/2/3/5/6/8/11/16/17 and VEGFA were markedly overexpressed, while CXCL12/13/14 were underexpressed in patients with COAD. Moreover, genetic alterations in the CXC chemokine-VEGFA network found at varying rates in patients with COAD were as follows: CXCL1/2/17 (2.1%), CXCL3/16 (2.6%), CXCL5/14 (2.4%), CXCL6 (3%), CXCL8 (0.8%), CXCL11/13 (1.9%), CXCL12 (0.6%), and VEGFA (1.3%). Promoter methylation of CXCL1/2/3/11/13/17 was considerably lower in patients with COAD, whereas methylation of CXCL5/6/12/14 and VEGFA was considerably higher. Furthermore, CXCL9/10/11 and VEGFA expression was notably correlated with the pathological stages of COAD. In addition, patients with COAD with high CXCL8/11/14 or low VEGFA expression levels survived longer than patients with dissimilar expression levels. CXC chemokines and VEGFA form a complex regulatory network through coexpression, colocalization, and genetic interactions. Moreover, many transcription factor targets of the CXC chemokine-VEGFA network in patients with COAD were identified: RELA, NFKB1, ZFP36, XBP1, HDAC2, SP1, ATF4, EP300, BRCA1, ESR1, HIF1A, EGR1, STAT3, and JUN. We further identified the top three miRNAs involved in regulating each CXC chemokine within the network: miR-518C, miR-369-3P, and miR-448 regulated CXCL1; miR-518C, miR-218, and miR-493 regulated CXCL2; miR-448, miR-369-3P, and miR-221 regulated CXCL3; miR-423 regulated CXCL13; miR-378, miR-381, and miR-210 regulated CXCL14; miR-369-3P, miR-382, and miR-208 regulated CXCL17; miR-486 and miR-199A regulated VEGFA. Furthermore, the CXC chemokine-VEGFA network in patients with COAD was notably associated with immune infiltration. Conclusions. This study revealed that the CXC chemokine-VEGFA network might act as a prognostic biomarker for patients with COAD. Moreover, our study provides new therapeutic targets for COAD, serving as a reference for further research in the future.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Systematic Analysis of CXC Chemokine–Vascular Endothelial Growth Factor A Network in Colonic Adenocarcinoma from the Perspective of Angiogenesis

Situ

Cui

et al. 2022

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…Patients with COAD also showed downregulated CXCL12/13/14 expression. The results were same with those in a previous study in patients with COAD 25 , and contradict previous ndings in patients with colorectal cancer 24 . This may be due to the small sample size and the many different types of colorectal cancer.…”

Section: Discussionsupporting

confidence: 86%

“…In recent years, studies have identi ed VEGFA and CXC chemokines as important participants in angiogenesis, particularly tumor angiogenesis 12,22,23 . The expression levels of CXC chemokines and VEGFA have been studied in a range of tumor types; however, ndings are contradictory with regard to colonic adenocarcinomas 24,25 . This study investigated expression level, gene regulatory network, prognostic value, and target prediction of the CXC chemokine-VEGFA network for COAD from the perspective of tumor angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Systematic analysis of CXC chemokine–vascular endothelial growth factor A network in colonic adenocarcinoma from the perspective of angiogenesis

Situ¹,

Deng

et al. 2022

Preprint

View full text Add to dashboard Cite

Background Tumor angiogenesis plays a vital role in tumorigenesis, proliferation, and metastasis. Recently, it has been gradually recognized that VEGFA and CXC chemokines are important players in angiogenesis. It is interesting to explore the expression level, gene regulatory network, prognostic value, and target prediction of CXC chemokine-VEGFA network in colon adenocarcinoma (COAD) from the perspective of tumor angiogenesis. Methods In this study, we analyzed gene expression and regulation, prognostic value, target prediction, and immune infiltrates related to CXC chemokine-VEGFA network in patients with COAD using multiple databases (cBioPortal, UALCAN, Human Protein Atlas, GeneMANIA, GEPIA, TIMER, TRRUST, LinkedOmics, and Metascape). Results Our results showed that CXCL1/2/3/5/6/8/11/16/17 and VEGFA were significantly overexpressed, while CXCL12/13/14 was underexpressed in patients with COAD. Moreover, genetic alterations in the CXC chemokine-VEGFA network found at varying rates in patients with COAD were as follows: CXCL1/2/17 (2.1%), CXCL3/16 (2.6%), CXCL5/14 (2.4%), CXCL6 (3%), CXCL8 (0.8%), CXCL11/13 (1.9%), CXCL12 (0.6%), and VEGFA (1.3%). Promoter methylation of CXCL1/2/3/11/13/17 was significantly lower in patients with COAD, while methylation of CXCL5/6/12/14 and VEGFA was significantly higher. Furthermore, CXCL9/10/11 and VEGFA expression was significantly correlated with the pathological stages of COAD. In addition, patients with COAD with high CXCL8/11/14 or low VEGFA expression levels survived longer than patients without these characteristics. CXC chemokines and VEGFA form a complex regulatory network through co-expression, co-localization, and genetic interactions. Moreover, many transcription factor targets of the CXC chemokine-VEGFA network in patients with COAD were found: RELA, NFKB1, ZFP36, XBP1, HDAC2, SP1, ATF4, EP300, BRCA1, ESR1, HIF1A, EGR1, STAT3, and JUN. We further identified the top three miRNAs involved in regulating each CXC chemokine within the network: miR-518C, miR-369-3P, and miR-448 regulated CXCL1; miR-518C, miR-218, and miR-493 regulated CXCL2; miR-448, miR-369-3P, and miR-221 regulated CXCL3; miR-423 regulated CXCL13; miR-378, miR-381, and miR-210 regulated CXCL14; miR-369-3P, miR-382, and miR-208 regulated CXCL17; miR-486 and miR-199A regulated VEGFA. Furthermore, the CXC chemokine-VEGFA network in patients with COAD was significantly associated with immune infiltration. Conclusions This study revealed that the CXC chemokine-VEGFA network is a prognostic biomarker for patients with COAD. Moreover, our study provides new therapeutic targets for COAD which will act as a reference for further research in the future.

show abstract

“…7 ). Prior studies found increased chemokine expression in tissues from colorectal cancer patients was associated with disease progression [ 85 , 86 ].…”

Section: Discussionmentioning

confidence: 99%

Sensory neuron dysfunction in orthotopic mouse models of colon cancer

Balogh

Zhang

Gaffney

et al. 2022

J Neuroinflammation

View full text Add to dashboard Cite

Reports of neurological sequelae related to colon cancer are largely restricted to rare instances of paraneoplastic syndromes, due to autoimmune reactions. Systemic inflammation associated with tumor development influences sensory neuron function in other disease models, though the extent to which this occurs in colorectal cancer is unknown. We induced orthotopic colorectal cancer via orthotopic injection of two colorectal cancer cell lines (MC38 and CT26) in two different mouse strains (C57BL/6 and Balb/c, respectively). Behavioral tests of pain sensitivity and activity did not detect significant alterations in sensory sensitivity or diminished well-being throughout tumor development. However, immunohistochemistry revealed widespread reductions in intraepidermal nerve fiber density in the skin of tumor-bearing mice. Though loss of nerve fiber density was not associated with increased expression of cell injury markers in dorsal root ganglia, lumbar dorsal root ganglia neurons of tumor-bearing animals showed deficits in mitochondrial function. These neurons also had reduced cytosolic calcium levels in live-cell imaging and reduced spontaneous activity in multi-electrode array analysis. Bulk RNA sequencing of DRGs from tumor-bearing mice detected activation of gene expression pathways associated with elevated cytokine and chemokine signaling, including CXCL10. This is consistent with the detection of CXCL10 (and numerous other cytokines, chemokines and growth factors) in MC38 and CT26 cell-conditioned media, and the serum of tumor-bearing mice. Our study demonstrates in a pre-clinical setting that colon cancer is associated with latent sensory neuron dysfunction and implicates cytokine/chemokine signaling in this process. These findings may have implications for determining risk factors and treatment responsiveness related to neuropathy in colorectal cancer.

show abstract

Comprehensive analysis of the prognosis and immune infiltration for CXC chemokines in colorectal cancer

Cited by 19 publications

References 39 publications

Systematic Analysis of CXC Chemokine–Vascular Endothelial Growth Factor A Network in Colonic Adenocarcinoma from the Perspective of Angiogenesis

Systematic Analysis of CXC Chemokine–Vascular Endothelial Growth Factor A Network in Colonic Adenocarcinoma from the Perspective of Angiogenesis

Systematic analysis of CXC chemokine–vascular endothelial growth factor A network in colonic adenocarcinoma from the perspective of angiogenesis

Sensory neuron dysfunction in orthotopic mouse models of colon cancer

Contact Info

Product

Resources

About