Bioinformatic Analysis of IKK Complex Genes Expression in Selected Gastrointestinal Cancers

Abstract

Gastrointestinal cancers account for over a quarter of all cancer cases and are associated with poor prognosis and high mortality rates. The IKK complex (the canonical I kappa B kinase), comprising the CHUK, IKBKB, and IKBKG genes, plays a crucial role in activating the NF-kB signaling pathway. This study aimed to analyze publicly available bioinformatics data to elucidate the oncogenic role of IKK genes in selected gastrointestinal cancers. Our findings reveal that IKBKB and IKBKG are significantly upregulated in all examined cancers, while CHUK is upregulated in esophageal carcinoma and stomach adenocarcinoma. Additionally, the expression of IKK genes varies with histological grade and nodal metastases. For instance, in stomach adenocarcinoma, CHUK and IKBKB are upregulated in higher histological grades and greater lymph node infiltration. Lower expression levels of CHUK, IKBKB, and IKBKG in stomach adenocarcinoma and IKBKB in esophageal squamous cell carcinoma correlate with shorter overall survival. Conversely, in esophageal adenocarcinoma, reduced IKBKG expression is linked to longer overall survival, while higher IKBKB expression in colon adenocarcinoma is associated with longer overall survival. Given the significant role of IKK genes in the development and progression of selected gastrointestinal cancers, they hold potential as prognostic markers and therapeutic targets, offering valuable insights for clinical practice.

Keywords: CHUK; IKBKB; IKBKG; expression; gastrointestinal cancer; prognostic marker.

Figure 1

The expression levels of (A) the CHUK gene, (B) the IKBKB gene, and (C) the IKBKG gene in pan-cancer using TIMER2.0, which showed expression in TCGA cancers (red box), the corresponding normal tissues (blue box) and metastasis tissue (purple box)wosuoyi; * p < 0.05; ** p < 0.01; *** p < 0.001 (Data for GI cancers are marked with red frames).

Figure 2

Expression profiling of IKK complex genes in GI cancers and normal tissue, from UALCAN: (A) CHUK gene; (B) IKBKB gene; (C) IKBKG gene in COAD; (D) CHUK gene (E) IKBKB gene; (F) IKBKG gene in ESCA; (G) CHUK gene; (H) IKBKB gene; (I) IKBKG gene in READ; (J) CHUK gene; (K) IKBKB gene; (L) IKBKG gene in STAD (tumor—red box, normal—blue box; * p < 0.05).

Figure 3

The expression level of (A) the CHUK gene in COAD, ESCA, READ, and STAD; (B) the IKBKB gene in COAD, ESCA, REDA, and STAD; and (C) the IKBKG gene in COAD, ESCA, READ, and STAD and corresponding normal tissue, from GEPIA (tumor—red box, normal—gray box; * p < 0.01).

Figure 4

Differences in IKK complex genes expression according to individual clinical cancer stage: (A) CHUK gene; (B) IKBKB gene; (C) IKBKG gene in COAD; (D) CHUK gene; (E) IKBKB gene; (F) IKBKG gene in ESCA; (G) CHUK gene; (H) IKBKB gene; (I) IKBKG gene in READ; (J) CHUK gene; (K) IKBKB gene; (L) IKBKG gene in STAD based on UALCAN web tool (* p < 0.05). Accessed 17–19 January 2023.

Figure 5

Differences in IKK complex genes expression according to nodal metastasis: (A) CHUK gene; (B) IKBKB gene; (C) IKBKG gene in COAD; (D) CHUK gene; (E) IKBKB gene; (F) IKBKG gene in ESCA; (G) CHUK gene; (H) IKBKB gene; (I) IKBKG gene in READ; (J) CHUK gene; (K) IKBKB gene; (L) IKBKG gene in STAD based on UALCAN web tool (* p < 0.05; N0—metastases into regional lymph node; N1—metastases in one to three axillary lymph nodes; N2—metastases in four to nine axillary lymph nodes; N3—metastases in ten or more axillary lymph nodes). Accessed 17–18 January 2023.

Figure 6

Differences in IKK complex genes expression according to histological grade: (A) CHUK gene, (B) IKBKB gene, (C) IKBKG gene in COAD; (D) CHUK gene, (E) IKBKB gene (F) IKBKG gene in STAD based on UALCAN web tool (* p < 0.05; Grade 1—well differentiated (low grade); Grade 2—moderately differentiated (intermediate grade); Grade 3—poorly differentiated (high grade). UALCAN, Access 17–18 January 2023.

Figure 7

The correlation of IKK complex genes expression with patient overall survival in (A) COAD, (B) EAC, (C) ESCA, (D) READ, and (E) STAD based on the Kaplan-Meier plotter (access: 4–5 September 2023).

Figure 8

Differential promoter methylation analysis of tumor samples versus normal ones: CHUK gene in (A) COAD, (B) ESCA, (C) READ, and (D) STAD; IKBKB gene in (E) COAD, (F) ESCA, (G) READ, and (H) STAD; and IKBKG gene in (I) COAD, (J) ESCA, (K) READ, and (L) STAD as assessed by UALCAN analysis (the beta value indicates the level of DNA methylation ranging from 0 (unmethylated) to 1 (fully methylated); hyper-methylation (Beta value: 0.7–0.5); or hypo-methylation (Beta-value: 0.3–0.25). (* p < 0.05; *** p <0.001) Accessed 4 September 2023.

Figure 9

The protein level in primary tumor vs. normal tissue of (A) CHUK, (B) IKBKB, (C) IKBKG, and according to the individual cancer clinical stage of (D) CHUK, (E) IKBKB, and (F) IKBKG, in COAD based on UALCAN (* p < 0.05; ** p < 0.01; z-values—standard deviations from the median across samples for COAD; Accessed 18–19 September 2023).