Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: NFKBIE

Gene summary for NFKBIE

Gene summary.

Gene information	Species	Human
	Gene symbol	NFKBIE
	Gene ID	4794
	Gene name	NFKB inhibitor epsilon
	Gene Alias	IKBE
	Cytomap	6p21.1
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	A0A024RD24

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
4794	NFKBIE	LZE20T	Human	Esophagus	ESCC	1.66e-08	1.96e-01	0.0662
4794	NFKBIE	LZE24T	Human	Esophagus	ESCC	7.74e-07	1.13e-01	0.0596
4794	NFKBIE	LZE21T	Human	Esophagus	ESCC	9.89e-04	1.63e-01	0.0655
4794	NFKBIE	P1T-E	Human	Esophagus	ESCC	3.35e-07	2.34e-01	0.0875
4794	NFKBIE	P2T-E	Human	Esophagus	ESCC	2.20e-25	4.45e-01	0.1177
4794	NFKBIE	P4T-E	Human	Esophagus	ESCC	1.77e-17	4.59e-01	0.1323
4794	NFKBIE	P5T-E	Human	Esophagus	ESCC	1.68e-07	2.29e-01	0.1327
4794	NFKBIE	P8T-E	Human	Esophagus	ESCC	4.47e-06	1.46e-01	0.0889
4794	NFKBIE	P9T-E	Human	Esophagus	ESCC	4.11e-10	2.46e-01	0.1131
4794	NFKBIE	P10T-E	Human	Esophagus	ESCC	7.57e-06	6.14e-02	0.116
4794	NFKBIE	P11T-E	Human	Esophagus	ESCC	1.13e-13	7.14e-01	0.1426
4794	NFKBIE	P12T-E	Human	Esophagus	ESCC	1.17e-07	1.69e-01	0.1122
4794	NFKBIE	P15T-E	Human	Esophagus	ESCC	4.00e-06	1.14e-01	0.1149
4794	NFKBIE	P16T-E	Human	Esophagus	ESCC	1.67e-15	2.73e-01	0.1153
4794	NFKBIE	P17T-E	Human	Esophagus	ESCC	1.40e-05	2.10e-01	0.1278
4794	NFKBIE	P19T-E	Human	Esophagus	ESCC	8.18e-03	2.39e-01	0.1662
4794	NFKBIE	P21T-E	Human	Esophagus	ESCC	3.65e-09	2.08e-01	0.1617
4794	NFKBIE	P22T-E	Human	Esophagus	ESCC	2.48e-11	2.44e-01	0.1236
4794	NFKBIE	P23T-E	Human	Esophagus	ESCC	1.45e-16	2.66e-01	0.108
4794	NFKBIE	P24T-E	Human	Esophagus	ESCC	1.82e-09	2.17e-01	0.1287

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:0045185111	Esophagus	ESCC	maintenance of protein location	71/8552	94/18723	3.41e-09	7.24e-08	71
GO:0051235110	Esophagus	ESCC	maintenance of location	200/8552	327/18723	1.01e-08	2.02e-07	200
GO:00510908	Esophagus	ESCC	regulation of DNA-binding transcription factor activity	252/8552	440/18723	5.22e-07	6.97e-06	252
GO:005122013	Esophagus	ESCC	cytoplasmic sequestering of protein	18/8552	22/18723	5.69e-04	3.10e-03	18
GO:00434332	Esophagus	ESCC	negative regulation of DNA-binding transcription factor activity	103/8552	185/18723	3.86e-03	1.57e-02	103
GO:00429943	Esophagus	ESCC	cytoplasmic sequestering of transcription factor	12/8552	15/18723	7.31e-03	2.63e-02	12
GO:00451857	Liver	Cirrhotic	maintenance of protein location	46/4634	94/18723	3.31e-07	7.90e-06	46
GO:005123511	Liver	Cirrhotic	maintenance of location	117/4634	327/18723	4.78e-06	7.86e-05	117
GO:00512202	Liver	Cirrhotic	cytoplasmic sequestering of protein	13/4634	22/18723	6.27e-04	4.80e-03	13
GO:0042994	Liver	Cirrhotic	cytoplasmic sequestering of transcription factor	9/4634	15/18723	3.88e-03	2.10e-02	9
GO:005123521	Liver	HCC	maintenance of location	185/7958	327/18723	1.70e-07	3.12e-06	185
GO:005122011	Liver	HCC	cytoplasmic sequestering of protein	20/7958	22/18723	3.00e-06	3.98e-05	20
GO:004518512	Liver	HCC	maintenance of protein location	61/7958	94/18723	9.61e-06	1.12e-04	61
GO:00429941	Liver	HCC	cytoplasmic sequestering of transcription factor	14/7958	15/18723	5.65e-05	5.26e-04	14
GO:00510902	Liver	HCC	regulation of DNA-binding transcription factor activity	220/7958	440/18723	8.04e-04	4.82e-03	220
GO:005123518	Oral cavity	OSCC	maintenance of location	182/7305	327/18723	6.16e-10	1.58e-08	182
GO:004518520	Oral cavity	OSCC	maintenance of protein location	65/7305	94/18723	3.00e-09	6.88e-08	65
GO:00510907	Oral cavity	OSCC	regulation of DNA-binding transcription factor activity	221/7305	440/18723	9.06e-07	1.23e-05	221
GO:00512204	Oral cavity	OSCC	cytoplasmic sequestering of protein	15/7305	22/18723	5.34e-03	2.07e-02	15
GO:00429942	Oral cavity	OSCC	cytoplasmic sequestering of transcription factor	11/7305	15/18723	7.49e-03	2.75e-02	11

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05169210	Esophagus	ESCC	Epstein-Barr virus infection	151/4205	202/8465	1.55e-13	3.45e-12	1.77e-12	151
hsa0472225	Esophagus	ESCC	Neurotrophin signaling pathway	80/4205	119/8465	7.33e-05	3.07e-04	1.57e-04	80
hsa052356	Esophagus	ESCC	PD-L1 expression and PD-1 checkpoint pathway in cancer	58/4205	89/8465	2.19e-03	6.16e-03	3.16e-03	58
hsa046599	Esophagus	ESCC	Th17 cell differentiation	68/4205	108/8465	3.53e-03	9.30e-03	4.76e-03	68
hsa046585	Esophagus	ESCC	Th1 and Th2 cell differentiation	58/4205	92/8465	6.49e-03	1.60e-02	8.19e-03	58
hsa046607	Esophagus	ESCC	T cell receptor signaling pathway	63/4205	104/8465	1.60e-02	3.60e-02	1.84e-02	63
hsa0516937	Esophagus	ESCC	Epstein-Barr virus infection	151/4205	202/8465	1.55e-13	3.45e-12	1.77e-12	151
hsa04722111	Esophagus	ESCC	Neurotrophin signaling pathway	80/4205	119/8465	7.33e-05	3.07e-04	1.57e-04	80
hsa0523511	Esophagus	ESCC	PD-L1 expression and PD-1 checkpoint pathway in cancer	58/4205	89/8465	2.19e-03	6.16e-03	3.16e-03	58
hsa0465914	Esophagus	ESCC	Th17 cell differentiation	68/4205	108/8465	3.53e-03	9.30e-03	4.76e-03	68
hsa0465812	Esophagus	ESCC	Th1 and Th2 cell differentiation	58/4205	92/8465	6.49e-03	1.60e-02	8.19e-03	58
hsa0466013	Esophagus	ESCC	T cell receptor signaling pathway	63/4205	104/8465	1.60e-02	3.60e-02	1.84e-02	63
hsa0516914	Liver	Cirrhotic	Epstein-Barr virus infection	80/2530	202/8465	1.80e-03	8.33e-03	5.13e-03	80
hsa0516915	Liver	Cirrhotic	Epstein-Barr virus infection	80/2530	202/8465	1.80e-03	8.33e-03	5.13e-03	80
hsa0516921	Liver	HCC	Epstein-Barr virus infection	128/4020	202/8465	3.17e-06	2.79e-05	1.55e-05	128
hsa0472210	Liver	HCC	Neurotrophin signaling pathway	74/4020	119/8465	8.27e-04	3.26e-03	1.81e-03	74
hsa049202	Liver	HCC	Adipocytokine signaling pathway	45/4020	69/8465	2.19e-03	7.55e-03	4.20e-03	45
hsa0516931	Liver	HCC	Epstein-Barr virus infection	128/4020	202/8465	3.17e-06	2.79e-05	1.55e-05	128
hsa0472211	Liver	HCC	Neurotrophin signaling pathway	74/4020	119/8465	8.27e-04	3.26e-03	1.81e-03	74
hsa049203	Liver	HCC	Adipocytokine signaling pathway	45/4020	69/8465	2.19e-03	7.55e-03	4.20e-03	45

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

NFKBIE

SNV

Missense_Mutation

rs768072245

c.704N>C

p.Arg235Pro

p.R235P

O00221

protein_coding

tolerated(0.19)

benign(0.077)

TCGA-A2-A04Q-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NFKBIE

SNV

Missense_Mutation

c.1498N>C

p.Asp500His

p.D500H

O00221

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.597)

TCGA-A8-A097-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

NFKBIE

SNV

Missense_Mutation

rs768072245

c.704G>C

p.Arg235Pro

p.R235P

O00221

protein_coding

tolerated(0.19)

benign(0.077)

TCGA-BH-A0DL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

NFKBIE

SNV

Missense_Mutation

rs768072245

c.704G>C

p.Arg235Pro

p.R235P

O00221

protein_coding

tolerated(0.19)

benign(0.077)

TCGA-C8-A133-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

NFKBIE

SNV

Missense_Mutation

novel

c.463T>C

p.Tyr155His

p.Y155H

O00221

protein_coding

tolerated(0.2)

benign(0.275)

TCGA-GI-A2C9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

NFKBIE

SNV

Missense_Mutation

novel

c.1376C>T

p.Ala459Val

p.A459V

O00221

protein_coding

tolerated(0.08)

probably_damaging(0.985)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NFKBIE

SNV

Missense_Mutation

novel

c.113N>A

p.Arg38Gln

p.R38Q

O00221

protein_coding

benign(0.022)

TCGA-C5-A7CK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NFKBIE

SNV

Missense_Mutation

novel

c.445N>A

p.Glu149Lys

p.E149K

O00221

protein_coding

deleterious(0.05)

benign(0.124)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NFKBIE

SNV

Missense_Mutation

c.1171N>T

p.Arg391Trp

p.R391W

O00221

protein_coding

deleterious(0)

benign(0.417)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

NFKBIE

SNV

Missense_Mutation

c.1171N>T

p.Arg391Trp

p.R391W

O00221

protein_coding

deleterious(0)

benign(0.417)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID

Symbol

Category

Interaction Types

Drug Claim Name

Drug Name

PMIDs

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