Danfeng Li,1,* Yongming Zeng,1,* Peilin Shen,2,* Xiaosheng Lin,1 Tian Yang,1 Binlie Chen,1,3 Zhiyan Ma,1,3 Huaiming Wang1
1Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China; 2Department of Urology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China; 3Medical College, Shantou University, Shantou, Guangdong, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Huaiming Wang
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College Email [email protected]
Purpose: This study aimed to explore the function and clinical significance of AVL9 in colorectal cancer (CRC).
Materials and Methods: The GEO, TCGA, and GEPIA databases were searched to evaluate the expression level of AVL9, while the SurvExpress online tool was used to explore its related clinical survival prognosis. The cBioPortal and LinkedOmics databases were used to identify AVL9 expression-related genes. Protein–protein interaction (PPI) networks were analyzed using Cytoscape 3.7.1 and DAVID6.8, which was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) signal pathway enrichment. The immunohistochemistry of AVL9 in CRC was detected using an online tool protein atlas. RNA isolation and reverse transcription–quantitative polymerase chain reaction (RT-qPCR) assays were used to detect AVL9 expression in tissue and plasma samples.
Results: Our study confirmed that AVL9 was highly expressed in CRC lesions versus the adjacent normal tissues (P < 0.001). High AVL9 expression was negatively associated with survival outcomes (P < 0.05). GO analysis showed that AVL9 expression-related genes were enriched in single organismal cell–cell adhesion, post-transcriptional regulation of gene expression, and negative regulation of the vascular endothelial growth factor receptor signaling pathway (P < 0.05). On a KEGG pathway analysis, these genes were mainly involved in progesterone-mediated oocyte maturation, axon guidance, the insulin signaling pathway, and the ubiquitin-mediated proteolysis signaling pathways (P < 0.05). In the PPI analysis, the KBTBD2, KIAA1147, EPDR1, and RNF216 genes interacted with AVL9, and GEPIA predicted that their expression levels were all positively correlated with AVL9. Furthermore, a clinicopathological parameter analysis found that high AVL9 expression was positively correlated with differentiation and TNM stage. RT-qPCR analysis further showed that plasma AVL9 expression was upregulated in CRC patients versus healthy controls.
Conclusion: AVL9 could serve as a potential biomarker and therapeutic target for CRC.
Keywords: AVL9, biomarker, colorectal cancer, prognosis
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