<p>CBX3 Promotes Gastric Cancer Progression and Affects Factors Related to Immunotherapeutic Responses</p>

Abstract

Background: Chromobox 3 (CBX3) is a member of the chromobox family proteins, which plays a critical role in tumor progression, but the exact function of CBX3 in gastric cancer remains unknown. The current research mainly investigates the underlying mechanisms and clinical value of CBX3 in gastric cancer. Methods: Gene expression cohorts from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to assess the effect of CBX3 in gastric cancer. CBX3 expression was further determined by immunohistochemistry (IHC). The function of CBX3 on proliferation, migration and the cell cycle was explored via colony-forming, cell cycle and transwell assays, respectively. Moreover, RNA sequencing (RNA-seq) in AGS cells and two cohorts was utilized to explore the specific mechanism of CBX3. Results: CBX3 expression was upregulated in human gastric cancer tissues and the expression level was closely associated with adverse signs. Knockdown of CBX3 in gastric cancer cells significantly inhibited the malignant phenotype. In addition, RNA-seq analysis revealed that CBX3 regulates genes related to the cell cycle, mismatch repair and immune-related pathways. Furthermore, the expression of CBX3 was significantly and inversely related to the abundance of tumor-infiltrating lymphocytes (TILs), PDCD1 and PDCD1LG2 expression and immunotherapy responses. Moreover, CBX3 influences the effectiveness of chemotherapy, thereby impacting the prognosis of gastric cancer patients. Conclusion: CBX3 contributes to gastric cancer progression and is associated with chemotherapy and immunotherapy response. CBX3 may serve as a new diagnostic biomarker and potential target for immunotherapy and chemotherapy in gastric cancer.

Comprehensive Analysis of the Expression and Prognosis Value of Chromobox Family Members in Clear Cell Renal Cell Carcinoma

“…Overexpression of CBX3 has also been observed in many malignancies such as lung cancer ( 43 , 44 ), gastric cancer ( 36 , 45 ), and tongue squamous cell carcinoma ( 46 , 47 ). High CBX3 targets CDKN1A to promote the proliferation of U87 cells and predicts poor recurrence-free survival and OS in glioma patients ( 48 ).…”

Evaluation of the prognostic value of CBXs in gastric cancer patients

“…For example, Lin et al found that overexpressed CBX3 contributes to the sensitivity of GC patients to chemotherapy. A survival advantage for the high CBX3 group compared with the low CBX3 group was observed in those who received chemotherapy 39 . The present study also showed that in GC patients receiving pharmaceutical therapy (HR 0.369, 95% CI 0.144–0.941, P = 0.037) and radiation therapy (HR 0.530, 95% CI 0.297–0.945, P = 0.031), the prognosis of the high CBX3 group was better than that of the low CBX3 group.…”

Prognosis and Immune Infiltration of Chromobox Family Genes in Sarcoma

“…In gastric cancer, Lin et al found that HP1-g (CBX3) was overexpressed and could regulate genes associated with the cell cycle, mismatch repair, and immune-related pathways. The expression level of HP1-g (CBX3) was also significantly and inversely related to the expression levels of TILs, PDCD1, and PDCD2, and immunotherapy responses, thus implying that HP1-g (CBX3) could influence the efficacy of immunotherapy and chemotherapy (33). Ma et al further confirmed the function and role of HP1-g (CBX3) in osteosarcoma, by showing that the expression of HP1-g (CBX3) was associated with a poorer DFS and OS, as well as a larger tumor size, a higher distant metastasis rate, and a higher clinical stage.…”

“…found that HP1-γ (CBX3) was overexpressed and could regulate genes associated with the cell cycle, mismatch repair, and immune-related pathways. The expression level of HP1- γ (CBX3) was also significantly and inversely related to the expression levels of TILs, PDCD1, and PDCD2, and immunotherapy responses, thus implying that HP1- γ (CBX3) could influence the efficacy of immunotherapy and chemotherapy ( 33 ). Ma et al.…”