Aryl hydrocarbon receptor is a prognostic biomarker and is correlated with immune responses in cervical cancer

Figures & data

Figure 1. The relationship between AHR and its associations and gene set enrichment analysis in cervical cancer based on the LinkedOmics database. Map of AHR-related genes(a). Heat map of the top 50 genes positively (b) and negatively (c) correlated with AHR. Gene set enrichment analysis of AHR (d)

Figure 2. Interactions between AHR and related proteins

Figure 3. Expression of AHR in GEO cervical cancer datasets. Expression of AHR in GSE7410(a), GSE67522(b)and GSE6791(c)

Table 1. The interaction scores of AHR with its related proteins

Gene	Annotation	Scores
CYP1A1	Cytochrome P450 1A1; Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes	0.997
ARNT2	Aryl hydrocarbon receptor nuclear translocator 2; Transcription factor that plays a role in the development of the hypothalamo-pituitary axis	0.989
HSP90AA1	Heat shock protein HSP 90-alpha; Molecular chaperone that promotes the maturation	0.989
ARNT	Aryl hydrocarbon receptor nuclear translocator; Required for activity of the Ah (dioxin) receptor. This protein is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding.	0.989
AIP	AH receptor-interacting protein; May play a positive role in AHR-mediated (aromatic hydrocarbon receptor) signaling	0.985
PTGES3	Prostaglandin E synthase 3; Cytosolic prostaglandin synthase that catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2).	0.974
HSP90AB1	Heat shock protein HSP 90-beta; Molecular chaperone that promotes the maturation	0.973
CYP1B1	Cytochrome P450 1B1; Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes	0.943
ESR1	Estrogen receptor; Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.	0.888
MAF	Transcription factor Maf; Acts as a transcriptional activator or repressor. Activates the expression of IL4 in T helper 2 (Th2) cells. Increases T-cell susceptibility to apoptosis by interacting with MYB and decreasing BCL2 expression.	0.871

Table 2. The expression of AHR and related genes in GEO data sets

Gene	GSE7410			GSE67522			GSE6791
	P	logFC		P	logFC		P	logFC
AHR	0.0204	−0.4101		0.0439	−0.3850		0.0081	−0.9289
CYP1A1	<0.001	1.1445		0.3300	0.0638		<0.001	0.5909
ARNT2	0.0027	0.5703		0.7710	0.0780		0.4460	−0.2506
HSP90AA1	0.0002	−0.8569		<0.001	−0.6930		<0.001	−1.8095
ARNT	<0.001	0.4053		0.2770	0.2080		<0.001	−1.0398
AIP	0.0863	−0.2581		0.2390	−0.2130		0.0959	−0.2656
PTGES3	<0.001	−0.7485		0.8230	−0.0369		<0.001	−1.8415
HSP90AB1	0.0010	−0.4403		0.4780	−0.1330		0.0001	−1.4151
CYP1B1	<0.001	1.5338		0.0005	1.5100		0.7630	−0.1137
ESR1	<0.001	2.2344		-	-		0.0464	0.2908
MAF	<0.001	0.9239		0.0003	1.3100		0.8690	0.0755

Figure 4. The expression of AHR and related genes was correlated with immune infiltration level in cervical cancer based on TIMER database. AHR(a), CYP1A1(b), ARNT2(c), HSP90AA1(d), ARNT(e), AIP(f), PTGES3(g), HSP90AB1(h), CYP1B1(i), ESR1(j)and MAF(k) with cervical cancer associated tumor sample purity, B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils, and dendritic cells

Figure 5. Correlations between AHR and related genes and immuno regulators in cervical cancer based on TISIDB database. The correlations between the expression of AHR, CYP1A1, HSP90AA1, PTGES3, CYP1B1, ESR1, and MAF and immunoinhibitors (a), immunostimulator (b), and MHC molecules (c) were calculated based on TISIDB database

Table 3. Multivariate Cox regression analysis

Expression	B	SE	Wald	HR	95%CI	P
AHR	0.628	0.286	4.812	1.874	1.069–3.285	0.028
CYP1A1	0.6	0.268	5.007	1.822	1.077–3.080	0.025

Figure 6. Alterations of AHR(a), CYP1A1(b), ARNT2(c), HSP90AA1(d), ARNT(e), AIP(f), PTGES3(g), HSP90AB1(h), CYP1B1(i), ESR1(j), MAF(k) were correlated with prognosis in cervical cancer patients based on the Kaplan-Meier database

Figure 7. Nomogram of factors associated with survival time in cervical cancer patients

Table 4. The positive expression of AHR and CYP1A1 in cervical tissue

Genes	Normal(n = 30)	Cancer(n = 30)	F	P
AHR	22.53 ± 16.47	50.22 ± 20.99	26.93	<0.001
CYP1A1	16.51 ± 7.31	38.07 ± 21.03	20.04	<0.001

Figure 8. The expression of AHR in normal (a), cancer (b). The expression of CYP1A1 in normal (c), cancer (d)