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: NCKAP1

Gene summary for NCKAP1

Gene summary.

Gene information	Species	Human
	Gene symbol	NCKAP1
	Gene ID	10787
	Gene name	NCK associated protein 1
	Gene Alias	HEM2
	Cytomap	2q32.1
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	Q9Y2A7

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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
10787	NCKAP1	CA_HPV_1	Human	Cervix	CC	4.13e-07	-2.48e-01	0.0264
10787	NCKAP1	CCI_1	Human	Cervix	CC	7.44e-05	8.39e-01	0.528
10787	NCKAP1	CCI_2	Human	Cervix	CC	5.78e-09	1.10e+00	0.5249
10787	NCKAP1	CCI_3	Human	Cervix	CC	1.88e-10	8.32e-01	0.516
10787	NCKAP1	Tumor	Human	Cervix	CC	2.29e-11	3.24e-01	0.1241
10787	NCKAP1	sample3	Human	Cervix	CC	4.30e-15	4.01e-01	0.1387
10787	NCKAP1	T3	Human	Cervix	CC	5.61e-16	3.65e-01	0.1389
10787	NCKAP1	HTA11_3410_2000001011	Human	Colorectum	AD	6.05e-12	-5.53e-01	0.0155
10787	NCKAP1	HTA11_696_2000001011	Human	Colorectum	AD	3.54e-03	-3.25e-01	-0.1464
10787	NCKAP1	HTA11_866_2000001011	Human	Colorectum	AD	2.39e-04	-4.01e-01	-0.1001
10787	NCKAP1	HTA11_866_3004761011	Human	Colorectum	AD	2.78e-04	-4.50e-01	0.096
10787	NCKAP1	HTA11_10711_2000001011	Human	Colorectum	AD	5.50e-03	-3.79e-01	0.0338
10787	NCKAP1	HTA11_7696_3000711011	Human	Colorectum	AD	2.46e-09	-4.48e-01	0.0674
10787	NCKAP1	HTA11_99999974143_84620	Human	Colorectum	MSS	1.73e-03	-3.45e-01	0.3005
10787	NCKAP1	F007	Human	Colorectum	FAP	4.64e-02	-3.32e-01	0.1176
10787	NCKAP1	A001-C-207	Human	Colorectum	FAP	4.91e-04	-3.06e-01	0.1278
10787	NCKAP1	A015-C-203	Human	Colorectum	FAP	1.36e-27	-5.11e-01	-0.1294
10787	NCKAP1	A015-C-204	Human	Colorectum	FAP	4.85e-06	-3.21e-01	-0.0228
10787	NCKAP1	A014-C-040	Human	Colorectum	FAP	4.20e-03	-3.56e-01	-0.1184
10787	NCKAP1	A002-C-201	Human	Colorectum	FAP	1.77e-13	-3.71e-01	0.0324

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal 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
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:01200347	Esophagus	ESCC	positive regulation of plasma membrane bounded cell projection assembly	64/8552	105/18723	1.15e-03	5.70e-03	64
GO:003086610	Esophagus	ESCC	cortical actin cytoskeleton organization	28/8552	40/18723	1.61e-03	7.50e-03	28
GO:00343156	Esophagus	ESCC	regulation of Arp2/3 complex-mediated actin nucleation	16/8552	21/18723	4.47e-03	1.76e-02	16
GO:00450108	Esophagus	ESCC	actin nucleation	33/8552	52/18723	7.38e-03	2.65e-02	33
GO:009758116	Esophagus	ESCC	lamellipodium organization	53/8552	90/18723	7.92e-03	2.82e-02	53
GO:190274515	Esophagus	ESCC	positive regulation of lamellipodium organization	24/8552	37/18723	1.46e-02	4.74e-02	24
GO:00072654	Liver	NAFLD	Ras protein signal transduction	66/1882	337/18723	8.43e-08	7.09e-06	66
GO:00070157	Liver	NAFLD	actin filament organization	78/1882	442/18723	5.44e-07	3.21e-05	78
GO:19029037	Liver	NAFLD	regulation of supramolecular fiber organization	66/1882	383/18723	8.97e-06	2.96e-04	66
GO:00329707	Liver	NAFLD	regulation of actin filament-based process	66/1882	397/18723	2.92e-05	7.72e-04	66
GO:19029057	Liver	NAFLD	positive regulation of supramolecular fiber organization	40/1882	209/18723	4.88e-05	1.15e-03	40
GO:00329567	Liver	NAFLD	regulation of actin cytoskeleton organization	60/1882	358/18723	5.20e-05	1.20e-03	60
GO:00975816	Liver	NAFLD	lamellipodium organization	22/1882	90/18723	6.25e-05	1.37e-03	22
GO:01100537	Liver	NAFLD	regulation of actin filament organization	49/1882	278/18723	6.88e-05	1.46e-03	49
GO:2000601	Liver	NAFLD	positive regulation of Arp2/3 complex-mediated actin nucleation	6/1882	10/18723	1.50e-04	2.78e-03	6
GO:00300324	Liver	NAFLD	lamellipodium assembly	18/1882	72/18723	2.09e-04	3.60e-03	18
GO:00313465	Liver	NAFLD	positive regulation of cell projection organization	57/1882	353/18723	2.19e-04	3.73e-03	57
GO:00432547	Liver	NAFLD	regulation of protein-containing complex assembly	66/1882	428/18723	2.83e-04	4.53e-03	66
GO:00512587	Liver	NAFLD	protein polymerization	49/1882	297/18723	3.54e-04	5.36e-03	49
GO:00343153	Liver	NAFLD	regulation of Arp2/3 complex-mediated actin nucleation	8/1882	21/18723	6.29e-04	8.21e-03	8

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0513020	Cervix	CC	Pathogenic Escherichia coli infection	63/1267	197/8465	9.28e-10	2.00e-08	1.19e-08	63
hsa0513220	Cervix	CC	Salmonella infection	74/1267	249/8465	1.33e-09	2.54e-08	1.50e-08	74
hsa0481016	Cervix	CC	Regulation of actin cytoskeleton	64/1267	229/8465	2.24e-07	2.59e-06	1.53e-06	64
hsa05130110	Cervix	CC	Pathogenic Escherichia coli infection	63/1267	197/8465	9.28e-10	2.00e-08	1.19e-08	63
hsa05132110	Cervix	CC	Salmonella infection	74/1267	249/8465	1.33e-09	2.54e-08	1.50e-08	74
hsa0481017	Cervix	CC	Regulation of actin cytoskeleton	64/1267	229/8465	2.24e-07	2.59e-06	1.53e-06	64
hsa05132	Colorectum	AD	Salmonella infection	102/2092	249/8465	7.65e-09	1.28e-07	8.17e-08	102
hsa05130	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa04810	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa051321	Colorectum	AD	Salmonella infection	102/2092	249/8465	7.65e-09	1.28e-07	8.17e-08	102
hsa051301	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa048101	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa051324	Colorectum	MSS	Salmonella infection	92/1875	249/8465	5.23e-08	9.74e-07	5.97e-07	92
hsa051304	Colorectum	MSS	Pathogenic Escherichia coli infection	73/1875	197/8465	1.10e-06	1.48e-05	9.06e-06	73
hsa048104	Colorectum	MSS	Regulation of actin cytoskeleton	68/1875	229/8465	4.27e-03	1.86e-02	1.14e-02	68
hsa051325	Colorectum	MSS	Salmonella infection	92/1875	249/8465	5.23e-08	9.74e-07	5.97e-07	92
hsa051305	Colorectum	MSS	Pathogenic Escherichia coli infection	73/1875	197/8465	1.10e-06	1.48e-05	9.06e-06	73
hsa048105	Colorectum	MSS	Regulation of actin cytoskeleton	68/1875	229/8465	4.27e-03	1.86e-02	1.14e-02	68
hsa051308	Colorectum	FAP	Pathogenic Escherichia coli infection	62/1404	197/8465	1.37e-07	3.08e-06	1.87e-06	62
hsa048106	Colorectum	FAP	Regulation of actin cytoskeleton	65/1404	229/8465	4.07e-06	5.91e-05	3.59e-05	65

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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

NCKAP1

SNV

Missense_Mutation

c.2730G>C

p.Leu910Phe

p.L910F

Q9Y2A7

protein_coding

deleterious(0)

possibly_damaging(0.548)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

NCKAP1

SNV

Missense_Mutation

c.1118N>G

p.Lys373Arg

p.K373R

Q9Y2A7

protein_coding

deleterious(0.01)

benign(0.315)

TCGA-A2-A0ER-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

NCKAP1

SNV

Missense_Mutation

c.1186N>T

p.Asp396Tyr

p.D396Y

Q9Y2A7

protein_coding

deleterious(0.02)

probably_damaging(0.918)

TCGA-A2-A1FW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

NCKAP1

SNV

Missense_Mutation

novel

c.2348N>G

p.Asp783Gly

p.D783G

Q9Y2A7

protein_coding

deleterious(0)

probably_damaging(0.981)

TCGA-AC-A5EH-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NCKAP1

SNV

Missense_Mutation

c.1372N>A

p.Cys458Ser

p.C458S

Q9Y2A7

protein_coding

deleterious(0)

benign(0.348)

TCGA-AN-A03X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NCKAP1

SNV

Missense_Mutation

c.3332N>A

p.Ser1111Tyr

p.S1111Y

Q9Y2A7

protein_coding

deleterious(0)

probably_damaging(0.916)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NCKAP1

SNV

Missense_Mutation

c.464N>A

p.Arg155Gln

p.R155Q

Q9Y2A7

protein_coding

deleterious(0.05)

benign(0.232)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NCKAP1

SNV

Missense_Mutation

c.1582C>T

p.His528Tyr

p.H528Y

Q9Y2A7

protein_coding

deleterious(0)

possibly_damaging(0.87)

TCGA-AN-A04A-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

NCKAP1

SNV

Missense_Mutation

c.2776N>A

p.Ala926Thr

p.A926T

Q9Y2A7

protein_coding

tolerated(0.16)

benign(0.112)

TCGA-C8-A135-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

NCKAP1

SNV

Missense_Mutation

novel

c.1937N>T

p.Ala646Val

p.A646V

Q9Y2A7

protein_coding

tolerated(0.23)

possibly_damaging(0.793)

TCGA-D8-A27W-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicine+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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