Published online Nov 15, 2022. doi: 10.4251/wjgo.v14.i11.2138
Peer-review started: July 9, 2022
First decision: July 31, 2022
Revised: August 30, 2022
Accepted: October 31, 2022
Article in press: October 31, 2022
Published online: November 15, 2022
Processing time: 128 Days and 16.4 Hours
Several genes, important for development, are reduced or silenced in adulthood, and their abnormal expression has been related to the occurrence and deve
To explore the expression pattern of six SIX proteins in CRCs and their re
The expression level of SIXs in normal tissues of different organs and related cancerous tissues was analyzed in the Human Protein Atlas. Kaplan-Meier Plotter and GEPIA2 were used to analyze the prognostic values of SIXs. To analyze the potential signaling pathways with SIX family involvement, LinkedOmics was used to perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of SIX4-related genes. Subsequently, immunohistochemical experiments were performed on CRC tissues and adjacent normal tissues, and we examined the SIX4 expression level in 87 pairs of patients with tissue microarray. The relationship between SIX4 and clinicopathological parameters in CRC patients was tested using the χ2 test and Fisher’s exact probability to verify the results of the database analysis.
The RNA levels of SIX1-4 and SIX6 were relatively low in normal human tissues, while SIX5 was highly expressed at both the RNA and protein levels. However, the protein level of SIX4 was found to be elevated in various malignancies. In CRC tissues, SIX1, SIX2 and SIX4 were elevated in cancer tissues compared with adjacent normal tissue. Among all SIXs, a high level of SIX4 was found to be associated with poor overall and disease-free survival in patients with CRC. For different clinicopathological parameters, increased SIX4 expression was positively correlated with advanced CRC. The top 50 SIX4-related genes were involved with oxidative phosphorylation and the respiratory chain signaling pathways.
The current results provided a comprehensive analysis of the expression and prognostic values of SIX family members in CRC. Among different SIXs, SIX4 plays an oncogenic role in CRC to promote the development of malignancy. In CRC, SIX4 mRNA and protein expression is higher than that in normal tissues and associated with shorter CRC patient survival, suggesting that SIX4 may be a potential therapeutic target for treatment of CRC patients.
Core Tip: This study systematically analyzed the expression pattern and prognostic value of sine oculis homeobox homolog (SIX) family members in colorectal cancer (CRC). It was found that the expression of SIX4 in CRC tissues positively correlated with the development of CRC and negatively correlated with overall survival. The top 50 SIX4-related genes were involved with oxidative phosphorylation and the respiratory chain signaling pathways. SIX4 may be a novel and potential therapeutic target for CRC.