Role of the CBX Molecular Family in Lung Adenocarcinoma Tumorigenesis and Immune Infiltration

Abstract

Background: The members of the Chromobox (CBX) family are important epigenetic regulatory molecules with critical biological roles in many tumors. However, no study has analyzed or verified their role in lung adenocarcinoma (LUAD).Methods: UALCAN and Oncomine databases were used to analyze CBX expression in LUAD, and the cBioPortal database was used to analyze CBX genetic variations. The Kaplan-Meier plotter and UALCAN databases were used to identify molecules with prognostic value. Gene Ontology pathway, receiver operating characteristic curves, and tumor-infiltrating immune cell analyses were used to clarify the biological function of the CBX hub molecules. Paired tumor samples and lung adenocarcinoma cell lines were collected for molecular functional assays to validate the results of the bioinformatics analysis.Results: CBX3/5 may have a cancer-promoting effect and its expression is associated with a poor patient prognosis, while CBX7 shows an opposite trend. CBX3/5/7 can regulate signaling pathways, regulate tumor immune cell infiltration, and has diagnostic value. Molecular biology experiments show that CBX3/5 is highly expressed in LUAD patients; in vitro it promotes the proliferation and migration of the LUAD cell line and can regulate the expression of the corresponding cytokines. CBX7 has opposite effects.Conclusion: Our bioinformatics analysis and subsequent experimental verification confirmed the CBX family members acted as hub signaling molecules in LUAD. The results provide new potential targets for the diagnosis and treatment of this cancer.

Chromobox proteins in cancer: Multifaceted functions and strategies for modulation (Review)

“…Expression of CBXs in cancers. Compared with normal tissues or paracancerous tissues, the expression of all or some of the CBX1/2/3/4/5/8 members is upregulated in most cancer tissues, including glioma (67-69), tongue squamous cell carcinoma (TSCC) (70), head and neck squamous cell carcinoma (HNSCC) (71), breast cancer (BC) (15,(72)(73)(74)(75)(76)(77)(78)(79)(80), non-small cell lung cancer (NSCLC) (81)(82)(83)(84)(85), esophageal cancer (EC) (86)(87)(88)(89)(90), gastric cancer (GC) (91)(92)(93)(94)(95)(96)(97)(98), pancreatic adenocarcinoma (PAAD) (99,100), colorectal cancer (CRC) (101-104), urinary bladder cancer (UBC) (105), sarcoma (106) and osteosarcoma (107,108). As a tumor suppressor, CBX7 is expressed at low levels in most tumors, such as glioma, HNSCC (71), EC (87,88), GC (93)(94)(95)(96)(97)(98), PAAD (109), CRC (103,104), clear cell r...…”

“…I, the expression of CBX3 is positively correlated with the tumor grade and/or stage of most cancer types, such as glioma and TSCC (70), lung adenocarcinoma (LUAD) (84), GC (91), HCC (116), CRC (101) and osteosarcoma (107), while the expression of CBX7 is negatively correlated with the tumor stage and grade of LUAD (84) and CCA (112). In addition, higher expression of CBX1/2/4/5/6/8 was associated with a higher tumor stage and grade in certain cancer types (11,67,69,74,76,80,84,86,90,99,104,108,111,118). Furthermore, higher expression of CBX3 was associated with a larger size of glioma (69) and osteosarcoma (107).…”

“…CBX4 is of prognostic value in BC (76,80), LUAD (85), EC (86)(87)(88), GC (92,94,95,98), HCC (11) and ccRCC (110). In addition, patients with BC (80), LUAD (84), GC (94)(95)(96)(97)(98), CRC (103), sarcoma (106), SKCM (113) with upregulated CBX5 and HNSCC (71) and ccRCC (110) with downregulated CBX5 have poor prognosis. CBX6 may be either a poor prognostic factor or a favorable prognostic factor, depending on the type of cancer (67,77,94,(96)(97)(98)(99)103,110,117,122).…”

“…CBX6 may be either a poor prognostic factor or a favorable prognostic factor, depending on the type of cancer (67,77,94,(96)(97)(98)(99)103,110,117,122). CBX7 acts as a tumor suppressor in glioma (68), BC (15,77), LUAD (83,84,125), HCC (114,119), PAAD (99,109), ccRCC (110), CCA (112), sarcoma (106) and SKCM (113). When the expression of CBX7 is low, the OS of patients is shorter, but its relationship to survival in EC (86)(87)(88) and GC (94-98) is controversial.…”

Integrative Analysis of Genetic and Epigenetic Alterations in the CBX7 Gene Reveals Its Tumor-Suppressive Function by Regulating the Cell Cycle in Human Breast Cancer

“…Recent studies have revealed the distinct Integrative Analysis of Genetic and Epigenetic Alterations in the CBX7 Gene Reveals Oncol Insights.2023;2:691 functions among CBX family members in cancer. For example, CBX3 was found to be upregulated, whereas CBX7 was downregulated in many types of human cancer [14][15][16][17][18][19][20][21][22]. Some studies have shown that CBX3 transcriptionally suppresses the p21 gene to promote cell proliferation [23][24][25], while CBX7 transcriptionally suppresses CCNE1 expression to inhibit cell proliferation [26].…”