Prognostic Value and Therapeutic Potential of CBX Family Members in Ovarian Cancer

Hu, Kuan; Yao, Lei; Xu, Zhijie; Yan, Yuanliang; Li, Juanni

doi:10.3389/fcell.2022.832354

Cited by 17 publications

(27 citation statements)

References 67 publications

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“…Moreover, CBX3 binding activity to methylated histone H3K9 was required to promote the proliferation of colorectal cancer [ 45 ] and lung cancer [ 46 ]. Recently, some researchers found that high expression of CBX3 promoted ovarian cancer cell proliferation and was significantly related to unfavorable progression and chemoresistance, impacting the treatment outcomes of OV patients [ 47 ]. Our results showed similar biological behavior of CBX3 in both RCC subtypes.…”

Section: Discussionmentioning

confidence: 99%

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CBX Family Members in Two Major Subtypes of Renal Cell Carcinoma: A Comparative Bioinformatic Analysis

Grimaldi¹,

Affinito²,

Salvatore³

et al. 2022

Diagnostics

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The biological function and clinical values of Chromobox (CBX) family proteins in renal cell carcinoma (RCC) are still poorly investigated. This study aimed to compare the expression profiles and clinical relevance of CBXs between the two most frequent subtypes of RCC, clear cell renal cell carcinomas (ccRCC) and papillary renal cell carcinomas (pRCC), and to investigate whether CBXs would play a more or less similar role in the pathogenesis and progression of these RCC subtypes. Considering these two RCC populations in the TCGA database, we built a bioinformatics framework by integrating a computational pipeline with several online tools. CBXs showed a similar trend in ccRCC and pRCC tissues but with some features specific for each subtype. Specifically, the relative expressions of CBX3 and CBX2 were, respectively, the highest and lowest among all CBXs in both RCC subtypes. These data also found confirmation in cellular validation. Except for CBX4 and CBX8, all others were deregulated in the ccRCC subtype. CBX1, CBX6, and CBX7 were also significantly associated with the tumor stage. Further, low expression levels of CBX1, CBX5, CBX6, CBX7, and high expression of CBX8 were associated with poor prognosis. Otherwise, in the pRCC subtype, CBX2, CBX3, CBX7, and CBX8 were deregulated, and CBX2, CBX6, and CBX7 were associated with the tumor stage. In addition, in pRCC patients, low expression levels of CBX2, CBX4, and CBX7 were associated with an unfavorable prognosis. Similarly, CBX3, CBX6, and CBX7 presented the highest alteration rate in both subtypes and were found to be functionally related to histone binding, nuclear chromosomes, and heterochromatin. Furthermore, CBX gene expression levels correlated with immune cell infiltration, suggesting that CBXs might reflect the immune status of RCC subtypes. Our results highlight similarities and differences of CBXs within the two major RCC subtypes, providing new insights for future eligible biomarkers or possible molecular therapeutic targets for these diseases.

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Section: Discussionmentioning

confidence: 99%

“…Mast cells are a kind of immune cell that can secrete diverse, active compounds to participate in the immune response. However, recent findings suggested that biological processes such as mast cell activation and mast cell-mediated immunity were regulated by the CBX family members in ovarian cancer [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

CBX Family Members in Two Major Subtypes of Renal Cell Carcinoma: A Comparative Bioinformatic Analysis

Grimaldi¹,

Affinito²,

Salvatore³

et al. 2022

Diagnostics

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“…Nowadays, it is well-established that the epigenetic dysregulation accelerates tumorigenesis, and at least partially, facilitates cancer stemness. Several reports suggest, that CBX family members possess the potential to become druggable targets in distinct tumor types, including breast, lung, ovarian, esophageal, and colon cancer [ 11 , 66 , 67 , 68 , 69 ]. However, these reports do not raise the question of therapeutic targeting of the stem cell-like phenotype of solid tumors and do not prove the engagement of CBX family members in molecular mechanism modulating cancer stemness.…”

Section: Discussionmentioning

confidence: 99%

Mining Transcriptomic Data to Uncover the Association between CBX Family Members and Cancer Stemness

Czerwińska

Maćkiewicz

2022

IJMS

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Genetic and epigenetic changes might facilitate the acquisition of stem cell-like phenotypes of tumors, resulting in worse patients outcome. Although the role of chromobox (CBX) domain proteins, a family of epigenetic factors that recognize specific histone marks, in the pathogenesis of several tumor types is well documented, little is known about their association with cancer stemness. Here, we have characterized the relationship between the CBX family members’ expression and cancer stemness in liver, lung, pancreatic, and uterine tumors using publicly available TCGA and GEO databases and harnessing several bioinformatic tools (i.e., Oncomine, GEPIA2, TISIDB, GSCA, UALCAN, R2 platform, Enrichr, GSEA). We demonstrated that significant upregulation of CBX3 and downregulation of CBX7 are consistently associated with enriched cancer stem-cell-like phenotype across distinct tumor types. High CBX3 expression is observed in higher-grade tumors that exhibit stem cell-like traits, and CBX3-associated gene expression profiles are robustly enriched with stemness markers and targets for c-Myc transcription factor regardless of the tumor type. Similar to high-stemness tumors, CBX3-overexpressing cancers manifest a higher mutation load. On the other hand, higher-grade tumors are characterized by the significant downregulation of CBX7, and CBX7-associated gene expression profiles are significantly depleted with stem cell markers. In contrast to high-stemness tumors, cancer with CBX7 upregulation exhibit a lower mutation burden. Our results clearly demonstrate yet unrecognized association of high CBX3 and low CBX7 expression with cancer stem cell-like phenotype of solid tumors.

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“…p value less than 0.05 was presumed to have statistical significance. The expression difference of UALCAN among each stage of OC was performed by using UALCAN database [23][24][25]. We used TCGA-OC to generate the coexpression gene network of PRNP in OC by using Xiantao tool (https:// www.xiantao.love) [26,27].…”

Section: Methodsmentioning

confidence: 99%

Downregulated PRNP Facilitates Cell Proliferation and Invasion and Has Effect on the Immune Regulation in Ovarian Cancer

Zhang

Zhou

et al. 2022

Journal of Immunology Research

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Background. Ovarian cancer (OC) seriously threatens women’s life. Ferroptosis plays an essential role in the initiation and development of OC. However, more molecular targets and mechanisms for ferroptosis in OC remain to be further elucidated. Methods. Several OC datasets were integrated in this study and three candidate genes including PRNP were further screened out as the ferroptosis-related gene which was differentially expressed in OC. Then, comprehensive evaluations concerning gene expression, clinical implication, in vitro validation of expression and functional experiments, prediction of downstream molecules and related signal pathways, and immune-modulating function were performed. Results. PRNP was the only downregulated ferroptosis-related gene with prognostic value for OC patients. The decreased mRNA and protein expression was verified in OC tissues and cell lines. PRNP was significantly correlated with cancer stages, primary therapy outcomes, and age in OC patients. Moreover, we found that overexpression of PRNP inhibited the proliferation, migration, and invasion ability of OC cells through in vitro experiments. PRNP was enriched to the Ras signaling pathway. PRNP expression was positively correlated with the infiltration of immune cells, such as mast cells, T effector memory cells, plasmacytoid DC cells, NK cells, and eosinophils. In addition, the association of PRNP with other immune signatures was also found. Conclusion. This study demonstrated for the first time showed that ferroptosis-related gene PRNP exerted a tumor suppressive role in OC and the aberrant expression and function of PRNP making it a potential novel biomarker for OC diagnosis, prognosis, and response to immunotherapies.

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Prognostic Value and Therapeutic Potential of CBX Family Members in Ovarian Cancer

Cited by 17 publications

References 67 publications

CBX Family Members in Two Major Subtypes of Renal Cell Carcinoma: A Comparative Bioinformatic Analysis

CBX Family Members in Two Major Subtypes of Renal Cell Carcinoma: A Comparative Bioinformatic Analysis

Mining Transcriptomic Data to Uncover the Association between CBX Family Members and Cancer Stemness

Downregulated PRNP Facilitates Cell Proliferation and Invasion and Has Effect on the Immune Regulation in Ovarian Cancer

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