F-box protein 22: A prognostic biomarker for colon cancer associated with immune infiltration and chemotherapy resistance

Figure 1 High expression of F-box protein 22 in colon adenocarcinoma. A: F-box protein 22 (FBXO22) expression levels in various types of cancer were analyzed by the Tumor Immunity Evaluation Resource 2.0 database (red box: Tumor tissues; blue box: Normal tissues); B: FBXO22 expression levels in various types of cancer were analyzed by the GENT2 database (red box: Tumor tissues; blue box: Normal tissues); C: FBXO22 mRNA expression in tumoral (blue) and normal (yellow) tissues; D: Immunohistochemistry analysis of FBXO22 expression in a colorectal cancer patient tissue (n = 80). FBXO22 levels in cancer tissues and corresponding normal tissues. Representative images are shown (40 ×). ^aP < 0.05, ^bP < 0.01, ^cP < 0.001 vs normal group; ^dP < 0.05 vs N group. ACC: Adrenocortical carcinoma; BLCA: Bladder urothelial carcinoma; BRCA: Breast invasive carcinoma; CESC: Cervical and endocervical cancers; CHOL: Cholangiocarcinoma; COAD: Colon adenocarcinoma; DLBC: Lymphoid neoplasm diffuse large B-cell lymphoma; ESCA: Esophageal carcinoma; GBM: Glioblastoma multiforme; HNSC: Head and neck squamous cell carcinoma; KICH: Kidney chromophobe; KIRC: Kidney renal clear cell carcinoma; KIRP: Kidney renal papillary cell carcinoma; LAML: Acute myeloid leukemia; LGG: Lower grade glioma; LIHC: Liver hepatocellular carcinoma; LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; MESO: Mesothelioma; OV: Ovarian serous cystadenocarcinoma; PAAD: Pancreatic adenocarcinoma; PCPG: Pheochromocytoma and paraganglioma; PRAD: Prostate adenocarcinoma; READ: Rectum adenocarcinoma; SARC: Sarcoma; SKCM: Skin cutaneous melanoma; STAD: Stomach adenocarcinoma; TGCT: Testicular germ cell tumors; THCA: Thyroid carcinoma; THYM: Thymoma; UCEC: Uterine corpus endometrial carcinoma; UCS: Uterine carcinosarcoma; UVM: Uveal melanoma.

Figure 2 Gene alterations are associated with dysregulation of F-box protein 22 expression in colorectal cancer patients. A and B: The most common mutations described in human colon cancer specimen. Green lollipops indicate the somatic mutations described in human colon cancer. The analysis was performed using cBioPortal for Cancer Genomics; C-K: F-box protein 22 mRNA expression dysregulation associated with promoter methylation level in colon adenocarcinoma. FBXO22: F-box protein 22; TCGA: The Cancer Genome Atlas; COAD: Colon adenocarcinoma.

Figure 3 F-box protein 22 related genes and functional enrichment analysis. A and B: Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis.

Figure 4 The correlation between various immune cell infiltration levels, expression of immune molecules, and F-box protein 22 expression in colon adenocarcinoma was analyzed using the Tumor Immunity Evaluation Resource 2. 0 and DNA methylation interactive visualization database platforms. A: The relationship between F-box protein 22 (FBXO22) expression and immune cell in colon adenocarcinoma (COAD); B: The relationship between FBXO22 expression and immune molecules in COAD, including immune suppressive molecules and immune stimulatory molecules; C: The relationship between FBXO22 expression and chemokine in COAD. FBXO22: F-box protein 22; TCGA: The Cancer Genome Atlas; COAD: Colon adenocarcinoma.

Figure 5 Comparison of chemotherapeutic effects in groups with high and low F-box protein 22 levels based on The Cancer Genome Atlas-colon adenocarcinoma cohort and analysed by R package oncoPredict. IC₅₀ was calculated for tipifarnib. FBXO22: F-box protein 22.

Figure 6 The prognostic significance of F-box protein 22 in colon adenocarcinoma patients. A and B: Kaplan-Meier curve analysis for the effect of F-box protein 22 expression on the prognosis of colon adenocarcinoma patients for overall survival; C: Kaplan-Meier curve analysis for the effect of F-box protein 22 expression on the prognosis of colon adenocarcinoma patients for progression-free survival. FBXO22: F-box protein 22; HR: Hazard ratio; PFI: Progression free interval.

Figure 7 Knockdown of the expression of F-box protein 22 inhibits proliferation, and migration of colon cancer cells in vitro. A: The transfection efficiency of si-F-box protein 22 (si-FBXO22) in the HCT116 cell lines and DLD1 cell lines were detected by polymerase chain reaction; B: The transfection efficiency of si-FBXO22 in the HCT116 cell lines and DLD1 cell lines were detected by western blotting; C and D: Cell Counting Kit-8 assay and 5-ethynyl-2’-deoxyuridine assay were applied to detect the efficiency of FBXO22 knockdown on the proliferation of HCT116 and DLD1 cell lines; E and F: Transwell migration assay and Wound-healing assay were applied to detect the efficiency of FBXO22 knockdown on the migration of HCT116 and DLD1 cell lines. ^aP < 0.01 vs blank group; ^bP < 0.001 vs blank group; ^cP < 0.001 vs negative control group; ^dP < 0.01 vs negative control group. FBXO22: F-box protein 22; NC: Negative control.