Basic Study
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World J Gastrointest Oncol. Nov 15, 2022; 14(11): 2138-2156
Published online Nov 15, 2022. doi: 10.4251/wjgo.v14.i11.2138
Comprehensive analysis of the potential role and prognostic value of sine oculis homeobox homolog family in colorectal cancer
Ze-Xuan Fang, Chun-Lan Li, Zheng Wu, Yan-Yu Hou, Hua-Tao Wu, Jing Liu
Ze-Xuan Fang, Chun-Lan Li, Zheng Wu, Yan-Yu Hou, Jing Liu, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
Hua-Tao Wu, Department of General Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
Author contributions: Liu J and Wu HT designed the research study; Fang ZX performed the research; Fang ZX, Li CL, Wu Z, Hou YY and Wu HT analyzed the research and wrote the manuscript; Liu J revised the manuscript critically; and all authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81501539; the Natural Science Foundation of Guangdong Province, No. 2021A1515012180 and 2016A030312008; Special Grant for Key Area Programs of Guangdong Department of Education, No. 2021ZDZX2004; Science and Technology Special Project of Guangdong Province, No. 210715216902829; “Dengfeng Project” for the construction of high-level hospitals in Guangdong Province-First Affiliated Hospital of Shantou University College Supporting Funding, No. 202003-10.
Institutional review board statement: The current study was reviewed and approved by the Ethics Committee of Shantou University Medical College.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jing Liu, MD, PhD, Academic Research, Associate Professor, Research Scientist, Senior Scientist, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, No. 22 Xinling Road, Shantou 515041, Guangdong Province, China. jliu12@stu.edu.cn
Received: July 9, 2022
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
ARTICLE HIGHLIGHTS
Research background

Human sine oculis homeobox homolog (SIX) protein belongs to the homeobox family, which plays an important role in different developmental organs, and the abnormal expression of most development-related genes is closely related to the occurrence and development of malignant tumors. However, no studies have comprehensively analyzed SIXs in colorectal cancer (CRC).

Research motivation

SIXs has been found to be closely related to the occurrence and development of cancer. However, there are few studies on SIXs in CRC. SIXs may become a new potential prognostic indicator of CRC.

Research objectives

To comprehensively analyze the expression and the prognosis of the SIX family in CRC tissues and to explore the potential role of the SIX family as a new prognostic indicator of CRC.

Research methods

In this study, the RNA and protein expression levels of the SIX family in CRC were analyzed by various online databases and immunohistochemically. Then the relationship between the SIX family and the prognosis of CRC was further analyzed. In order to better understand the mechanism of SIX4, the positive correlation between SIX4 expression and tumor-node-metastasis stage of CRC was analyzed. Then, the relationship between SIX4 mRNA levels and clinicopathological parameters in CRC patients was analyzed.

Research results

The expression levels of SIXs in most organs were relatively low in the Human Protein Atlas. UCSC Xena database analysis showed that the expression levels of SIX1, SIX2 and SIX4 in CRC were higher than those in corresponding normal tissue. Further survival analysis with Kaplan-Meier Plotter showed that the relation between poor overall survival and disease-free survival of CRC patients and high SIX4 expression were significant. Using the LinkedOmics database, the expression of SIX4 was positively correlated with the clinical stage, T stage and N stage of CRC, and the top 50 SIX4-related genes were involved in oxidative phosphorylation and respiratory chain signaling pathway, suggesting that SIX4 was involved in promoting the growth and metastasis of CRC.

Research conclusions

As a member of the SIX family, SIX4 played a role in promoting tumor development in the intestine, which may serve as a potential prognostic indicator and therapeutic target for CRC patients. Therefore, targeting SIX4 may serve as a new therapeutic strategy for CRC patients, providing important potential for the treatment of CRC.

Research perspectives

This is the first comprehensive analysis of the potential role and prognostic value of the SIX family in CRC. However, the current research is limited, and future studies need to further explore the oxidative phosphorylation, respiratory chain activity and metabolism of SIX4 in CRC.