P1178 - Higher Expression of CTHRC1 in Tumor Tissues Is Associated With Poor Prognosis in Colorectal Cancer: A Bioinformatical Analysis

Monday, October 25, 2021

10:30 AM – 4:15 PM PT

Location: Shoreline Exhibit Hall

Has Audio

Presenting Author(s)

Chenyu Sun, MD, MSc

AMITA Health Saint Joseph Hospital
Chicago, IL, United States

Chenyu Sun, MD, MSc¹, Na Hyun Kim, MD¹, John Pocholo W. Tuason, MD¹, Chandur Bhan, MD¹, Sudha Misra, MD¹, Zain I. Siddiqui, MD¹, Yasmin A. Gerais, MD¹, Mohammed R. Gandam, MD¹, Jannell F. Lising, MD¹, Jie Liu, MD²
¹AMITA Health Saint Joseph Hospital, Chicago, IL; ²The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China

Introduction: The aim of this bioinformatical analysis study was to identify genes with worse prognoses of colorectal cancer (CRC).

Methods: Gene expression profiles of GSE110224 & GSE113513 were extracted from GEO database. Differentially expressed genes (DEGs) between CRC and normal colorectal specimen were identified via GEO2R online tools with |logFC| > 2 and adjust P value < 0.05. Then, the raw data were checked in Venn software online to detect the common DEGs of the two datasets. The DEGs with log FC > 2 were considered as an up-regulated gene. Gene ontology (GO) analysis and KEGG pathway analysis were used to identify unique biological properties and pathways. DAVID online bioinformatics tool was used to visualize the DEGs enrichment of BP, MF, CC, and pathways (P < 0.05). PPI information was evaluated by STRING (Search Tool for the Retrieval of Interacting Genes) and Cytoscape. Survival analysis and RNA sequencing expression were conducted on GEPIA website with default settings. An immunohistochemical staining sample was obtained from The Human Protein Atlas open database for demonstration.

Results: There are 31 CRC &31 normal tissue samples in the two profile datasets, and 61 upregulated DEGs from GSE110224 and 79 upregulated DEGs from GSE113513 were extracted via GEO2R. Then Venn diagram detected 30 commonly up-regulated DEGs in the GC tissues. GO analysis of the DEGs indicated that they were enriched in chemokine-mediated signaling pathway, positive regulation of neutrophil chemotaxis, and collagen catabolic process for biological processes (BP), and enriched in extracellular space, extracellular region, and proteinaceous extracellular matrix for GO cell component (CC), and enriched in CXCR chemokine receptor binding, c chemokine activity, and growth factor activity for molecular function (MF). KEGG analysis results found that they were enriched in Cytokine-cytokine receptor interaction, Legionellosis, and Chemokine signaling pathway. Analysis of PPI network complex included 29 nodes and 41 edges. Survival analysis identified CTHRC1 was associated with a worse prognosis (P < 0.05), and GEPIA found its expression was higher in CRC tissues than normal tissue. Immunohistochemical staining of CRC sample from 62-year-old male found medium staining and moderate intensity.

Discussion: CTHRC1, an up-regulated DEG with a poor prognosis of CRC and higher expression cancer tissue, was identified based on integrated bioinformatical methods, which could be potential therapeutic targets for CRC patients.

Figure: A) Volcano plots of GSE110224 and GSE113513; B) Authentication of 30 common up-regulated DEGs (logFC>2) in the two datasets (GSE1100224, and GSE113513) through Venn diagrams software; C) Common DEGs PPI network constructed by STRING online database and Cytoscape; D) CTHRC1 had significant expression level in CRC cancer specimen compared to normal specimen (*P < 0.05), red color means tumor tissues and grey color means normal tissues; E) CTHRC1 was associated with a significantly worse survival rate (P < 0.05); F) Immunohistochemical staining of CRC sample from 62-year-old male obtained from The Human Protein Atlas open database found medium staining and moderate intensity.

DEGS		Genes Name
Up-regulated		CDH3 INHBA CXCL1 CHI3L1 TCN1 COL11A1 CXCL3 CEMIP MMP1 GDF15 TRIM29 MMP7 CTHRC1 SERPINB5 CXCL8 CRNDE CXCL2 CLDN1 TACSTD2 FOXQ1 REG1A MMP3 EPHX4 TESC MSX2 KRT23 REG3A DUSP27 DPEP1 CXCL5
	Category		Term	Count	%	p-Value	FDR
Up-regulated DEG	GOTERM_BP_DIRECT		chemokine-mediated signaling pathway	5	16.7	4.1E-6	6.1E-4
			positive regulation of neutrophil chemotaxis	4	13.3	5.0E-6	6.1E-4
			collagen catabolic process	4	13.3	5.0E-6	6.1E-4
	GOTERM_CC_DIRECT		extracellular space	15	50.0	1.1E-9	4.0E-8
			extracellular region	13	43.3	1.1E-6	2.0E-5
			proteinaceous extracellular matrix	6	20.0	4.1E-5	5.1E-4
	GOTERM_MF_DIRECT		CXCR chemokine receptor binding	4	13.3	3.4E-7	2.2E-5
			chemokine activity	5	16.7	1.2E-6	3.9E-5
			growth factor activity	4	13.3	2.4E-3	5.1E-2
KEGG			Cytokine-cytokine receptor interaction	6	20.0	5.4E-5	2.0E-3
			Legionellosis	13.3	1.2E-4	2.4E-3	13.3
			Chemokine signaling pathway	5	16.7	3.1E-4	3.9E-3

Table: All 30 commonly differentially expressed genes (DEGs) were detected from two profile datasets, of which all are up-regulated genes in the CRC tissues compared to normal tissues; Gene ontology analysis and KEGG pathway analysis of differentially expressed genes in CRC

Disclosures:

Chenyu Sun indicated no relevant financial relationships.

Na Hyun Kim indicated no relevant financial relationships.

John Pocholo Tuason indicated no relevant financial relationships.

Chandur Bhan indicated no relevant financial relationships.

Sudha Misra indicated no relevant financial relationships.

Zain Siddiqui indicated no relevant financial relationships.

Yasmin Gerais indicated no relevant financial relationships.

Mohammed Gandam indicated no relevant financial relationships.

Jannell Lising indicated no relevant financial relationships.

Jie Liu indicated no relevant financial relationships.

Chenyu Sun, MD, MSc¹, Na Hyun Kim, MD¹, John Pocholo W. Tuason, MD¹, Chandur Bhan, MD¹, Sudha Misra, MD¹, Zain I. Siddiqui, MD¹, Yasmin A. Gerais, MD¹, Mohammed R. Gandam, MD¹, Jannell F. Lising, MD¹, Jie Liu, MD². P1178 - Higher Expression of CTHRC1 in Tumor Tissues Is Associated With Poor Prognosis in Colorectal Cancer: A Bioinformatical Analysis, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.