Breast Cancer: Targets and Therapy (Dec 2022)
Chromobox Family Proteins as Putative Biomarkers for Breast Cancer Management: A Preliminary Study Based on Bioinformatics Analysis and qRT-PCR Validation
Abstract
Hao Tian,1,* Tingting Zhao,1,* Yanling Li,1,* Na Sun,1 Dandan Ma,1 Qiyun Shi,1 Guozhi Zhang,1 Qingqiu Chen,1 Kongyong Zhang,1 Ceshi Chen,2,* Yi Zhang,1 Xiaowei Qi1 1Department of Breast and Thyroid Surgery, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaowei Qi; Yi Zhang, Department of Breast and Thyroid Surgery, Southwest Hospital, Army Medical University, Gaotanyan Street 29, Chongqing, 400038, People’s Republic of China, Tel/Fax +86-23-68754160, Email [email protected]; [email protected]: Epigenetic modification of chromatin is an important step in the regulation of gene expression. The chromobox family proteins (CBXs), as epigenetic modifier, may play a vital role in tumorigenesis and cancer progression. Herein we explored the correlation between CBXs and breast cancer (BC) via the bioinformatics approach and qRT-PCR validation.Methods: Several databases, including GEPIA, TCGA, GEO, K-M plotter, STRING, DAVID, cBioPortal, CIBERSORT, and HPA were employed to analyze the expression levels of CBXs and the correlations between CBXs and prognosis (overall and recurrence-free survival) in BC. We analyzed molecular functions, genetic variations, transcription factors of CBXs, and immune cell infiltration status. ROC curve analysis was performed to determine the predictive value of CBXs. RNA extracted from 11 human BC and paired adjacent normal tissues were subjected to qRT-PCR.Results: The mRNA expression level of CBX1– 5 was significantly upregulated, while that of CBX7 was significantly downregulated in BC; no expression disparities were observed in CBX6/8 expression. Further, high mRNA expression of CBX1/2/3/4/8 correlated with advanced BC, whereas high mRNA expression of CBX6/7 correlated with early BC. High mRNA expressions of CBX1/2/3/5 predict poor OS and RFS, while higher mRNA expressions of CBX6/7 predict better OS and RFS in patients with BC. ROC curve analysis revealed that CBX3 showed excellent discriminatory ability. Gene ontology enrichment analysis showed that CBXs primarily participated in SUMOylation and post-/transcriptional regulation. Moreover, they presented varying degrees of amplification in BC tissues and were related to the infiltration of various immune cells.Conclusion: CBXs can serve as putative biomarkers for BC. Further studies are warranted to determine the exact molecular mechanisms underlying the action of CBXs in BC, particularly CBX1/2/3/5/7.Keywords: chromobox family proteins, breast cancer, prognosis, bioinformatics, qRT-PCR
