Integrated analysis of genes associated with poor prognosis of patients with colorectal cancer liver metastasis

Qian, Zhenyuan; Zhang, Guobing; Song, Guangyuan; Gong, Lijie; Mou, Yiping; Han, Yong

doi:10.18632/oncotarget.16064

Cited by 38 publications

(24 citation statements)

References 40 publications

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“…Notably, THBS2 is known to activate transforming growth factor-β1 (TGF-β1) signaling, which promotes metastasis 20. A recent study shows that overexpression of THBS2 correlated with poor OS and RFS in CRC patients, which is consistent with our results 21. SERPINE1 expression has been shown to be associated with tumor cell migration and invasion through the activation of the PI3K-Akt pathway 22–24.…”

Section: Discussionsupporting

confidence: 90%

Computational analysis of mRNA expression profiles identifies a novel triple-biomarker model as prognostic predictor of stage II and III colorectal adenocarcinoma patients

Cheng¹,

Hu²,

Chen³

et al. 2018

CMAR

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IntroductionAlthough remarkable progress has been made to determine the prognosis of patients with colorectal cancer (CRC), it is inadequate to identify the subset of high-risk TNM stage II and stage III patients that have a high potential of developing tumor recurrence and may experience death. In this study, we aimed to develop biomarkers as a prognostic signature for the clinical outcome of CRC patients with stage II and stage III.Materials and methodsWe performed a systematic and comprehensive discovery step to identify recurrence-associated genes in CRC patients through publicly available GSE41258 (n=253) and GSE17536 (n=107) datasets. We subsequently determined the prognostic relevance of candidate genes in stage II and III patients and developed a triple-biomarker for predicting RFS in GSE17536, which was later validated in an independent cohort GSE33113 dataset (n=90).ResultsBased upon mRNA expression profiling studies, we identified 45 genes which differentially expressed in recurrent vs non-recurrent CRC patients. By using Cox proportional hazard models, we then developed a triple-marker model (THBS2, SERPINE1, and FN1) to predict prognosis in GSE17536, which successfully identified poor prognosis in stage II and stage III, particularly high-risk stage II CRC patients.DiscussionNotably, we found that our triple-marker model once again predicted recurrence in stage II patients in GSE33113. Kaplan–Meier survival analysis demonstrated that patients with high scores have a poor outcome compared to those with low scores. Our triple-marker model is a reliable predictive tool for determining prognosis in CRC patients with stage II and stage III, and might be able to identify high-risk patients that are candidates for more targeted personalized clinical management and surveillance.

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Section: Discussionsupporting

confidence: 90%

Computational analysis of mRNA expression profiles identifies a novel triple-biomarker model as prognostic predictor of stage II and III colorectal adenocarcinoma patients

Cheng¹,

Hu²,

Chen³

et al. 2018

CMAR

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“…For example, periostin (POSTN), which has previously been reported to promote cell motility in several cancer types, was 13‐fold higher expressed in the metastases compared to nondiseased tissue (Gillan et al ., ; Ishiba et al ., ; Mikheev et al ., ). The most upregulated (>100‐fold) protein in the metastases was thrombospondin‐2 (THBS2) and is also involved in cell invasion as well as angiogenesis and correlates with poor survival (Bornstein, ; Iruela‐Arispe et al ., ; Lin et al ., ; Qian et al ., ; Wang et al ., ). Another protein driving cell invasion, methylthioribose‐1‐phosphate isomerase (MRI1) was highly significantly upregulated but only 1.9‐fold (Kabuyama et al ., ).…”

Section: Resultsmentioning

confidence: 99%

Rapid proteomic analysis for solid tumors revealsLSD1 as a drug target in an end‐stage cancer patient

et al. 2018

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Recent advances in mass spectrometry (MS)‐based technologies are now set to transform translational cancer proteomics from an idea to a practice. Here, we present a robust proteomic workflow for the analysis of clinically relevant human cancer tissues that allows quantitation of thousands of tumor proteins in several hours of measuring time and a total turnaround of a few days. We applied it to a chemorefractory metastatic case of the extremely rare urachal carcinoma. Quantitative comparison of lung metastases and surrounding tissue revealed several significantly upregulated proteins, among them lysine‐specific histone demethylase 1 (LSD1/KDM1A). LSD1 is an epigenetic regulator and the target of active development efforts in oncology. Thus, clinical cancer proteomics can rapidly and efficiently identify actionable therapeutic options. While currently described for a single case study, we envision that it can be applied broadly to other patients in a similar condition.

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“…However, the expression level of TLR2 or TLR4 is only slightly increased in colon cancer samples according to the GENT2 database. Instead of TLR2 or TLR4, BGN (which is significantly increased in colon cancer) may be a more useful marker in human colorectal cancer [32].…”

Section: Discussionmentioning

confidence: 99%

BGN/TLR4/NF-κB Mediates Epigenetic Silencing of Immunosuppressive Siglec Ligands in Colon Cancer Cells

Huang

Cai

Suen

et al. 2020

Cells

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Human Toll-like receptor (TLR) signaling plays a vital role in intestinal inflammation by activating the NF-κB pathway. By querying GENT2 datasets, we identified the gene expression level of TLR2 and TLR4 as being substantially increased in colorectal cancer. Introduction of shRNAs for TLR4 but not TLR2 dramatically recovered disialyl Lewis a and sialyl 6-sulfo Lewis x glycans, which are preferentially expressed in non-malignant colonic epithelial cells and could serve as ligands for the immunosuppressive molecule Siglec-7. We screened several TLR4 ligands and found that among them BGN is highly expressed in cancers and is involved in the epigenetic silencing of Siglec-7 ligands. Suppression of BGN expression substantially downregulated NF-κB activity and the marker H3K27me3 in the promoter regions of the SLC26A2 and ST6GalNAc6 genes, which are involved in the synthesis of those glycans, and restored expression of normal glycans as well as Siglec-7 binding activities. We show that in the presence of TLR4, inflammatory stimuli initiate a positive loop involving NF-κB that activates BGN and further enhances TLR4 activity. Present findings indicate a putative mechanism for the promotion of carcinogenesis by loss of immunosuppressive ligands by the BGN/TLR4/ NF-κB pathway.

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Integrated analysis of genes associated with poor prognosis of patients with colorectal cancer liver metastasis

Cited by 38 publications

References 40 publications

Computational analysis of mRNA expression profiles identifies a novel triple-biomarker model as prognostic predictor of stage II and III colorectal adenocarcinoma patients

Computational analysis of mRNA expression profiles identifies a novel triple-biomarker model as prognostic predictor of stage II and III colorectal adenocarcinoma patients

Rapid proteomic analysis for solid tumors revealsLSD1 as a drug target in an end‐stage cancer patient

BGN/TLR4/NF-κB Mediates Epigenetic Silencing of Immunosuppressive Siglec Ligands in Colon Cancer Cells

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