CESC is one of the deadliest diseases originating from cervical cells. Squamous cell carcinoma and are the most common pathological subtypes accounting for approximately 70%, and adenocarcinoma accounting for approximately 25% of all CESC. Since the 3-year to 5-year survival rate of patients with CESC in many developing countries is < 50%, early detection, effective therapy, and precise prediction of the outcome are of great significance for CESC patients [1, 5, 21].
Although most cervical cancer cases are due to human papillomavirus (HPV) infection, additional genetic and epigenetic changes are required for cervical carcinogenesis . Recently, advances in understanding the biology of CESC have shown that epigenetic alterations are common in the tumorigenesis of CESC and metastasis . Therefore, novel biomarkers related to the prognosis and treatment of CESC are urgently needed.
In our study, the expression level, mutation status, and prognostic value of eight members of the CBX family in CESC were analyzed. We mainly focused on the relationship between the CBXs mRNA expression level and the prognosis of patients with CESC. We revealed that CESC patients with high CBX7 levels had a favorable prognosis, demonstrating CBX7 as a potential prognostic biomarker for CESC.
The CBX family is a canonical component of PcG and is implicated in the development of diversified cancers . CBX1 is a member of the heterochromatin protein 1 (HP1) family, also known as HP1β. Yang et al. found that the expression level of CBX1 was significantly increased in HCC tissues and cell lines and was significantly correlated with tumor size, degree of differentiation, and tumor aggressiveness . Analogously, Shiota et al. found that CBX1 expression was increased in prostate cancer samples. Additionally, its high expression could enhance the activity of the androgen receptor pathway and accelerate the growth of prostate cancer .
Recently, Clermont et al. conducted a Geno transcriptomic meta-analysis and found high CBX2 mRNA expression in human cancer. In particular, overexpression and amplification of CBX2 were significantly correlated with metastatic progression and a shorter OS of BC patients . Meanwhile, Wheeler et al. found that CBX2 upregulation promotes high-grade serous ovarian carcinoma by inducing a stem-like transcriptional profile and inhibiting anoikis . Mechanistically, studies from Zhao et al., Ma et al., and Chen et al. showed that CBX3 is overexpressed in gliomas, osteosarcoma, and pancreatic adenocarcinoma, and upregulated CBX3 is indicative of a worse OS[28–30].
CBX4 has been thoroughly studied in a variety of cancers. Jiao et al. and Wang et al. respectively found that CBX4 was highly expressed in clinical specimens and multiple hepatocellular carcinoma cells. It was also associated with clinical parameters, including the α-fetoprotein level, tumor size, lymph node metastasis, distant metastasis, pathologic differentiation, shorter OS, and relapse-free survival (RFS) [31, 32]. Additional studies carried out by Li et al. showed that CBX4 was overexpressed in HCC mice and promoted tumorigenesis by increasing VEGF production and angiogenesis, while knockdown of CBX4 suppressed the tumorigenicity of CBX4 . Furthermore, Hu et al. indicated that CBX4 is overexpressed in lung cancer cells and promotes proliferation and metastasis by regulating the BMI-1 . CBX5 also known as heterochromatic protein 1α (HP1α), and overexpression of CBX5 was found in many types of malignant tumors, including pancreatic cancers, breast cancers, and lung cancers .
In a previous report, Zheng et al. found that the higher expression of CBX6 in HCC promotes the growth of hepatocellular carcinoma cells by regulating the pathway: S100A9/NF-κB/MAPK and hepatocellular carcinoma patients with higher CBX6 expression had significantly shorter RFS and OS . Studies carried out by Li et al. showed that CBX6 was downregulated in glioblastoma multiforme cells and clinical tissues. In addition, overexpression of CBX6 suppressed the proliferation of glioblastoma multiforme cells .
Different characteristics of CBX7 have been found in multiple types of human cancers. Pallante et al. reported that CBX7 is decreased in diversified human malignant tumors, including thyroid cancers, breast cancers, lung carcinomas, colorectal cancers, and bladder cancers. Additionally, decreased expression of CBX7 has been shown to significantly correlate with higher metastasis and a worse prognosis of patients. Mechanistically, CBX7 inhibits the expression of proliferation and migration genes containing CCNE and SPP1 by counteracting the carcinogenesis of HMGA proteins . Shinjo et al. found that higher expression of CBX7 is significantly associated with worse overall and progression-free survival rates in ovarian cancer patients . And Li et al. found that CBX7 inhibits tumor growth and metastatic potential by binding to the E-box to inhibit TWIST-1 function in ovarian cancer . In our study, we found that CBX7 expression was decreased in CESC tissues compared to adjusted normal tissues, while higher mRNA expression of CBX7 was significantly associated with a favorable OS (overall survival) in CESC patients. In addition, The CBX7 protein expression was not detected in CESC tissues demonstrated by immunohistochemistry pictures. These results indicate that CBX7 is an effective marker for predicting the outcomes of patients.
Similarly, CBX8 plays a significant role in lymphoma, breast carcinoma, esophageal squamous cell carcinoma, esophageal cancer, and other human cancers . Studies carried out by Yuan et al. showed that upregulated CBX8 was associated with the progression of the stages in muscle-invasive bladder cancer tissues by repressing the p53 pathway . Coincidentally, CBX8 inhibits metastasis by suppressing the Snail pathway in esophageal squamous cell carcinoma while promoting cell proliferation .
In conclusion, we found that high expression of CBX7 mRNA is significantly related to the favorable prognosis and survival of CESC patients. Other members of the CBX family have no obvious relationship with prognosis and survival. Certainly, there are some limitations to our study, and all of the data researched in our study were acquired from online databases. Further research requires a larger sample size to test our findings and to explore the clinical application and potential mechanisms of CBX members in the treatment of CESC.