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: NKAP

Gene summary for NKAP

Gene summary.

Gene information	Species	Human
	Gene symbol	NKAP
	Gene ID	79576
	Gene name	NFKB activating protein
	Gene Alias	MRXSHD
	Cytomap	Xq24
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q8N5F7

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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
79576	NKAP	LZE2T	Human	Esophagus	ESCC	3.10e-02	2.57e-01	0.082
79576	NKAP	LZE4T	Human	Esophagus	ESCC	2.39e-12	3.93e-01	0.0811
79576	NKAP	LZE5T	Human	Esophagus	ESCC	6.37e-04	3.09e-01	0.0514
79576	NKAP	LZE7T	Human	Esophagus	ESCC	1.72e-16	7.74e-01	0.0667
79576	NKAP	LZE8T	Human	Esophagus	ESCC	3.36e-08	1.49e-01	0.067
79576	NKAP	LZE20T	Human	Esophagus	ESCC	1.46e-03	2.46e-01	0.0662
79576	NKAP	LZE24T	Human	Esophagus	ESCC	1.82e-28	7.18e-01	0.0596
79576	NKAP	LZE21T	Human	Esophagus	ESCC	2.08e-08	4.42e-01	0.0655
79576	NKAP	LZE6T	Human	Esophagus	ESCC	1.13e-05	3.05e-01	0.0845
79576	NKAP	P1T-E	Human	Esophagus	ESCC	3.99e-13	6.70e-01	0.0875
79576	NKAP	P2T-E	Human	Esophagus	ESCC	1.22e-52	8.37e-01	0.1177
79576	NKAP	P4T-E	Human	Esophagus	ESCC	2.11e-31	7.44e-01	0.1323
79576	NKAP	P5T-E	Human	Esophagus	ESCC	5.97e-16	3.19e-01	0.1327
79576	NKAP	P8T-E	Human	Esophagus	ESCC	1.07e-22	5.29e-01	0.0889
79576	NKAP	P9T-E	Human	Esophagus	ESCC	6.62e-26	6.46e-01	0.1131
79576	NKAP	P10T-E	Human	Esophagus	ESCC	3.23e-44	7.86e-01	0.116
79576	NKAP	P11T-E	Human	Esophagus	ESCC	3.02e-21	6.41e-01	0.1426
79576	NKAP	P12T-E	Human	Esophagus	ESCC	1.40e-20	4.52e-01	0.1122
79576	NKAP	P15T-E	Human	Esophagus	ESCC	3.84e-19	4.16e-01	0.1149
79576	NKAP	P16T-E	Human	Esophagus	ESCC	1.79e-23	3.59e-01	0.1153

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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
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:004578527	Esophagus	ESCC	positive regulation of cell adhesion	255/8552	437/18723	5.07e-08	9.11e-07	255
GO:00072197	Esophagus	ESCC	Notch signaling pathway	106/8552	172/18723	1.74e-05	1.55e-04	106
GO:1903706110	Esophagus	ESCC	regulation of hemopoiesis	201/8552	367/18723	2.60e-04	1.58e-03	201
GO:19021076	Esophagus	ESCC	positive regulation of leukocyte differentiation	93/8552	157/18723	4.20e-04	2.39e-03	93
GO:19037086	Esophagus	ESCC	positive regulation of hemopoiesis	93/8552	157/18723	4.20e-04	2.39e-03	93
GO:002240720	Esophagus	ESCC	regulation of cell-cell adhesion	239/8552	448/18723	5.88e-04	3.19e-03	239
GO:004211018	Esophagus	ESCC	T cell activation	256/8552	487/18723	1.18e-03	5.87e-03	256
GO:19031317	Esophagus	ESCC	mononuclear cell differentiation	226/8552	426/18723	1.20e-03	5.88e-03	226
GO:002240919	Esophagus	ESCC	positive regulation of cell-cell adhesion	155/8552	284/18723	1.50e-03	7.06e-03	155
GO:190210510	Esophagus	ESCC	regulation of leukocyte differentiation	152/8552	279/18723	1.82e-03	8.35e-03	152
GO:00456213	Esophagus	ESCC	positive regulation of lymphocyte differentiation	61/8552	104/18723	5.22e-03	1.97e-02	61
GO:005087015	Esophagus	ESCC	positive regulation of T cell activation	117/8552	216/18723	7.23e-03	2.62e-02	117
GO:00302176	Esophagus	ESCC	T cell differentiation	137/8552	257/18723	8.09e-03	2.87e-02	137
GO:190303916	Esophagus	ESCC	positive regulation of leukocyte cell-cell adhesion	128/8552	239/18723	8.40e-03	2.96e-02	128
GO:000715918	Esophagus	ESCC	leukocyte cell-cell adhesion	192/8552	371/18723	1.03e-02	3.51e-02	192
GO:190303717	Esophagus	ESCC	regulation of leukocyte cell-cell adhesion	174/8552	336/18723	1.36e-02	4.43e-02	174
GO:00300984	Esophagus	ESCC	lymphocyte differentiation	192/8552	374/18723	1.52e-02	4.93e-02	192
GO:00457857	Liver	Cirrhotic	positive regulation of cell adhesion	141/4634	437/18723	2.05e-04	1.89e-03	141
GO:004578512	Liver	HCC	positive regulation of cell adhesion	215/7958	437/18723	2.53e-03	1.22e-02	215
GO:004578520	Oral cavity	OSCC	positive regulation of cell adhesion	225/7305	437/18723	6.06e-08	1.09e-06	225

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

NKAP

SNV

Missense_Mutation

c.1097N>A

p.Arg366Gln

p.R366Q

Q8N5F7

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AC-A2QI-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

NKAP

SNV

Missense_Mutation

c.983N>A

p.Gly328Glu

p.G328E

Q8N5F7

protein_coding

deleterious(0.02)

probably_damaging(0.995)

TCGA-C8-A1HG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NKAP

SNV

Missense_Mutation

rs200925009

c.331N>A

p.Asp111Asn

p.D111N

Q8N5F7

protein_coding

tolerated(0.12)

benign(0.015)

TCGA-C8-A26V-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

tamoxiphen

NKAP

SNV

Missense_Mutation

c.1167N>C

p.Glu389Asp

p.E389D

Q8N5F7

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

NKAP

SNV

Missense_Mutation

c.1103G>A

p.Arg368Gln

p.R368Q

Q8N5F7

protein_coding

deleterious(0.01)

probably_damaging(0.99)

TCGA-OL-A66J-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NKAP

insertion

Frame_Shift_Ins

novel

c.600_601insGAGTCTCCTTTTTGTACTCTCTCCTGGCTGATGATTGACCAGAAGG

p.Ser201GlufsTer22

p.S201Efs*22

Q8N5F7

protein_coding

TCGA-A2-A0CM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NKAP

SNV

Missense_Mutation

c.605N>T

p.Ser202Leu

p.S202L

Q8N5F7

protein_coding

tolerated(0.22)

possibly_damaging(0.603)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NKAP

SNV

Missense_Mutation

novel

c.64N>T

p.Arg22Cys

p.R22C

Q8N5F7

protein_coding

deleterious(0)

possibly_damaging(0.446)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NKAP

SNV

Missense_Mutation

c.1042N>C

p.Glu348Gln

p.E348Q

Q8N5F7

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

NKAP

SNV

Missense_Mutation

c.1103G>A

p.Arg368Gln

p.R368Q

Q8N5F7

protein_coding

deleterious(0.01)

probably_damaging(0.99)

TCGA-EK-A2PG-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

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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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