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: NFKBIZ

Gene summary for NFKBIZ

Gene summary.

Gene information	Species	Human
	Gene symbol	NFKBIZ
	Gene ID	64332
	Gene name	NFKB inhibitor zeta
	Gene Alias	IKBZ
	Cytomap	3q12.3
	Gene Type	protein-coding
	GO ID	GO:0001775
	UniProtAcc	Q9BYH8

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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
64332	NFKBIZ	GSM4909281	Human	Breast	IDC	1.54e-07	-3.73e-01	0.21
64332	NFKBIZ	GSM4909285	Human	Breast	IDC	4.65e-14	-4.71e-01	0.21
64332	NFKBIZ	GSM4909286	Human	Breast	IDC	1.83e-25	-5.67e-01	0.1081
64332	NFKBIZ	GSM4909294	Human	Breast	IDC	8.25e-19	-5.13e-01	0.2022
64332	NFKBIZ	GSM4909296	Human	Breast	IDC	1.76e-18	-4.68e-01	0.1524
64332	NFKBIZ	GSM4909297	Human	Breast	IDC	1.50e-19	-4.61e-01	0.1517
64332	NFKBIZ	GSM4909298	Human	Breast	IDC	8.95e-09	-4.10e-01	0.1551
64332	NFKBIZ	GSM4909301	Human	Breast	IDC	1.09e-17	-5.17e-01	0.1577
64332	NFKBIZ	GSM4909302	Human	Breast	IDC	8.77e-12	-4.72e-01	0.1545
64332	NFKBIZ	GSM4909304	Human	Breast	IDC	4.06e-10	-4.51e-01	0.1636
64332	NFKBIZ	GSM4909306	Human	Breast	IDC	1.34e-16	-5.07e-01	0.1564
64332	NFKBIZ	GSM4909311	Human	Breast	IDC	3.92e-26	-4.17e-01	0.1534
64332	NFKBIZ	GSM4909312	Human	Breast	IDC	2.21e-18	-5.06e-01	0.1552
64332	NFKBIZ	GSM4909315	Human	Breast	IDC	4.02e-03	-2.92e-01	0.21
64332	NFKBIZ	GSM4909316	Human	Breast	IDC	1.27e-02	-4.33e-01	0.21
64332	NFKBIZ	GSM4909319	Human	Breast	IDC	1.40e-34	-6.12e-01	0.1563
64332	NFKBIZ	GSM4909320	Human	Breast	IDC	1.90e-07	-5.59e-01	0.1575
64332	NFKBIZ	GSM4909321	Human	Breast	IDC	3.67e-09	1.20e-01	0.1559
64332	NFKBIZ	brca1	Human	Breast	Precancer	5.47e-04	-3.15e-01	-0.0338
64332	NFKBIZ	brca2	Human	Breast	Precancer	1.28e-03	-2.73e-01	-0.024

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗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:19031314	Cervix	CC	mononuclear cell differentiation	76/2311	426/18723	5.66e-04	5.42e-03	76
GO:00456192	Cervix	CC	regulation of lymphocyte differentiation	37/2311	174/18723	6.06e-04	5.69e-03	37
GO:0002768	Cervix	CC	immune response-regulating cell surface receptor signaling pathway	59/2311	315/18723	6.64e-04	6.11e-03	59
GO:00466342	Cervix	CC	regulation of alpha-beta T cell activation	25/2311	104/18723	7.13e-04	6.46e-03	25
GO:00026973	Cervix	CC	regulation of immune effector process	62/2311	339/18723	9.25e-04	7.84e-03	62
GO:00026967	Cervix	CC	positive regulation of leukocyte activation	72/2311	409/18723	1.13e-03	9.31e-03	72
GO:00512516	Cervix	CC	positive regulation of lymphocyte activation	65/2311	362/18723	1.15e-03	9.39e-03	65
GO:00508676	Cervix	CC	positive regulation of cell activation	73/2311	420/18723	1.50e-03	1.16e-02	73
GO:00508524	Cervix	CC	T cell receptor signaling pathway	27/2311	123/18723	1.93e-03	1.42e-02	27
GO:00466353	Cervix	CC	positive regulation of alpha-beta T cell activation	17/2311	67/18723	2.62e-03	1.81e-02	17
GO:00024603	Cervix	CC	adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	62/2311	356/18723	3.09e-03	2.03e-02	62
GO:0002263	Cervix	CC	cell activation involved in immune response	50/2311	279/18723	4.16e-03	2.57e-02	50
GO:0002699	Cervix	CC	positive regulation of immune effector process	43/2311	235/18723	5.13e-03	3.02e-02	43
GO:0002819	Cervix	CC	regulation of adaptive immune response	35/2311	183/18723	5.38e-03	3.11e-02	35
GO:00300981	Cervix	CC	lymphocyte differentiation	63/2311	374/18723	6.21e-03	3.52e-02	63
GO:0002822	Cervix	CC	regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	32/2311	168/18723	8.00e-03	4.18e-02	32
GO:00466312	Cervix	CC	alpha-beta T cell activation	30/2311	156/18723	8.73e-03	4.48e-02	30
GO:19021073	Cervix	CC	positive regulation of leukocyte differentiation	30/2311	157/18723	9.56e-03	4.73e-02	30
GO:19037083	Cervix	CC	positive regulation of hemopoiesis	30/2311	157/18723	9.56e-03	4.73e-02	30
GO:004578515	Cervix	HSIL_HPV	positive regulation of cell adhesion	48/737	437/18723	1.37e-10	4.72e-08	48

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa052028	Esophagus	ESCC	Transcriptional misregulation in cancer	116/4205	193/8465	2.08e-03	5.95e-03	3.05e-03	116
hsa0520213	Esophagus	ESCC	Transcriptional misregulation in cancer	116/4205	193/8465	2.08e-03	5.95e-03	3.05e-03	116
hsa052026	Lung	IAC	Transcriptional misregulation in cancer	40/1053	193/8465	6.90e-04	5.90e-03	3.92e-03	40
hsa0520211	Lung	IAC	Transcriptional misregulation in cancer	40/1053	193/8465	6.90e-04	5.90e-03	3.92e-03	40
hsa052022	Lung	AIS	Transcriptional misregulation in cancer	39/961	193/8465	2.15e-04	2.41e-03	1.54e-03	39
hsa052023	Lung	AIS	Transcriptional misregulation in cancer	39/961	193/8465	2.15e-04	2.41e-03	1.54e-03	39
hsa052024	Lung	MIAC	Transcriptional misregulation in cancer	22/507	193/8465	2.64e-03	2.26e-02	1.64e-02	22
hsa052025	Lung	MIAC	Transcriptional misregulation in cancer	22/507	193/8465	2.64e-03	2.26e-02	1.64e-02	22
hsa052027	Prostate	BPH	Transcriptional misregulation in cancer	53/1718	193/8465	9.56e-03	2.92e-02	1.81e-02	53
hsa0520212	Prostate	BPH	Transcriptional misregulation in cancer	53/1718	193/8465	9.56e-03	2.92e-02	1.81e-02	53
hsa0520221	Prostate	Tumor	Transcriptional misregulation in cancer	59/1791	193/8465	1.22e-03	5.26e-03	3.26e-03	59
hsa0520231	Prostate	Tumor	Transcriptional misregulation in cancer	59/1791	193/8465	1.22e-03	5.26e-03	3.26e-03	59

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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

NFKBIZ

SNV

Missense_Mutation

c.727N>C

p.Val243Leu

p.V243L

Q9BYH8

protein_coding

deleterious_low_confidence(0.03)

benign(0.015)

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NFKBIZ

SNV

Missense_Mutation

c.1165G>C

p.Glu389Gln

p.E389Q

Q9BYH8

protein_coding

tolerated(0.29)

benign(0.056)

TCGA-A2-A0YK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

NFKBIZ

SNV

Missense_Mutation

novel

c.876N>C

p.Gln292His

p.Q292H

Q9BYH8

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.671)

TCGA-A7-A4SA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

NFKBIZ

SNV

Missense_Mutation

novel

c.1100A>G

p.Asn367Ser

p.N367S

Q9BYH8

protein_coding

tolerated_low_confidence(0.65)

benign(0)

TCGA-A8-A09D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

NFKBIZ

SNV

Missense_Mutation

novel

c.2083G>A

p.Asp695Asn

p.D695N

Q9BYH8

protein_coding

tolerated(0.06)

probably_damaging(0.914)

TCGA-AR-A2LE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

NFKBIZ

SNV

Missense_Mutation

c.1621N>G

p.Gln541Glu

p.Q541E

Q9BYH8

protein_coding

tolerated(0.06)

possibly_damaging(0.474)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

NFKBIZ

SNV

Missense_Mutation

c.1445N>T

p.Ser482Ile

p.S482I

Q9BYH8

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-E9-A1NA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

NFKBIZ

SNV

Missense_Mutation

novel

c.403N>G

p.Ser135Ala

p.S135A

Q9BYH8

protein_coding

tolerated_low_confidence(0.07)

benign(0.003)

TCGA-GM-A3NY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

NFKBIZ

insertion

Nonsense_Mutation

novel

c.1876_1877insAACATATAAGATGATATCTGTTTTGAAAGCTCCTGAAAGATTTTA

p.Leu626delinsGlnHisIleArgTerTyrLeuPheTerLysLeuLeuLysAspPheMet

p.L626delinsQHIR*YLF*KLLKDFM

Q9BYH8

protein_coding

TCGA-A8-A07L-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

NFKBIZ

insertion

Nonsense_Mutation

novel

c.791_792insAGATTTCAGATTTTCAGATTAGGGATACTCAACTGTATTATTA

p.Pro265AspfsTer7

p.P265Dfs*7

Q9BYH8

protein_coding

TCGA-AO-A0J2-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

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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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