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: NCK1

Gene summary for NCK1

Gene summary.

Gene information	Species	Human
	Gene symbol	NCK1
	Gene ID	4690
	Gene name	NCK adaptor protein 1
	Gene Alias	NCK
	Cytomap	3q22.3
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	P16333

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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
4690	NCK1	CA_HPV_3	Human	Cervix	CC	3.58e-12	3.65e-01	0.0414
4690	NCK1	CCI_2	Human	Cervix	CC	8.56e-14	1.30e+00	0.5249
4690	NCK1	CCI_3	Human	Cervix	CC	4.83e-14	1.12e+00	0.516
4690	NCK1	Tumor	Human	Cervix	CC	1.25e-14	4.54e-01	0.1241
4690	NCK1	sample3	Human	Cervix	CC	3.08e-24	5.08e-01	0.1387
4690	NCK1	T1	Human	Cervix	CC	1.70e-05	3.82e-01	0.0918
4690	NCK1	T3	Human	Cervix	CC	2.19e-19	5.12e-01	0.1389
4690	NCK1	LZE2T	Human	Esophagus	ESCC	7.35e-05	6.02e-01	0.082
4690	NCK1	LZE4T	Human	Esophagus	ESCC	9.53e-23	8.88e-01	0.0811
4690	NCK1	LZE5T	Human	Esophagus	ESCC	8.61e-05	6.22e-01	0.0514
4690	NCK1	LZE7T	Human	Esophagus	ESCC	8.27e-11	5.11e-01	0.0667
4690	NCK1	LZE8T	Human	Esophagus	ESCC	3.48e-15	8.20e-01	0.067
4690	NCK1	LZE20T	Human	Esophagus	ESCC	2.71e-05	2.45e-01	0.0662
4690	NCK1	LZE22D1	Human	Esophagus	HGIN	9.62e-04	1.03e-01	0.0595
4690	NCK1	LZE22T	Human	Esophagus	ESCC	6.40e-05	6.22e-01	0.068
4690	NCK1	LZE24T	Human	Esophagus	ESCC	1.88e-21	8.37e-01	0.0596
4690	NCK1	LZE22D3	Human	Esophagus	HGIN	6.64e-04	3.79e-01	0.0653
4690	NCK1	LZE6T	Human	Esophagus	ESCC	3.92e-08	5.15e-01	0.0845
4690	NCK1	P1T-E	Human	Esophagus	ESCC	7.54e-09	7.75e-01	0.0875
4690	NCK1	P2T-E	Human	Esophagus	ESCC	1.23e-69	1.25e+00	0.1177

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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
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

∗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:19038975	Oral cavity	OSCC	regulation of PERK-mediated unfolded protein response	10/7305	11/18723	5.78e-04	3.30e-03	10
GO:004209816	Oral cavity	OSCC	T cell proliferation	100/7305	199/18723	7.93e-04	4.27e-03	100
GO:002240917	Oral cavity	OSCC	positive regulation of cell-cell adhesion	136/7305	284/18723	1.35e-03	6.62e-03	136
GO:00109984	Oral cavity	OSCC	regulation of translational initiation by eIF2 alpha phosphorylation	9/7305	10/18723	1.36e-03	6.62e-03	9
GO:1902237	Oral cavity	OSCC	positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	9/7305	10/18723	1.36e-03	6.62e-03	9
GO:00300328	Oral cavity	OSCC	lamellipodium assembly	41/7305	72/18723	1.53e-03	7.31e-03	41
GO:00466263	Oral cavity	OSCC	regulation of insulin receptor signaling pathway	38/7305	66/18723	1.70e-03	8.07e-03	38
GO:19000763	Oral cavity	OSCC	regulation of cellular response to insulin stimulus	37/7305	64/18723	1.76e-03	8.31e-03	37
GO:190303910	Oral cavity	OSCC	positive regulation of leukocyte cell-cell adhesion	115/7305	239/18723	2.48e-03	1.09e-02	115
GO:005087010	Oral cavity	OSCC	positive regulation of T cell activation	104/7305	216/18723	3.76e-03	1.55e-02	104
GO:00331354	Oral cavity	OSCC	regulation of peptidyl-serine phosphorylation	72/7305	144/18723	4.66e-03	1.87e-02	72
GO:00364904	Oral cavity	OSCC	regulation of translation in response to endoplasmic reticulum stress	9/7305	11/18723	4.85e-03	1.92e-02	9
GO:00109763	Oral cavity	OSCC	positive regulation of neuron projection development	80/7305	163/18723	5.54e-03	2.14e-02	80
GO:00480132	Oral cavity	OSCC	ephrin receptor signaling pathway	29/7305	51/18723	7.33e-03	2.71e-02	29
GO:00706618	Oral cavity	OSCC	leukocyte proliferation	145/7305	318/18723	9.31e-03	3.33e-02	145
GO:00069293	Oral cavity	OSCC	substrate-dependent cell migration	15/7305	23/18723	9.84e-03	3.46e-02	15
GO:00466517	Oral cavity	OSCC	lymphocyte proliferation	131/7305	288/18723	1.41e-02	4.67e-02	131
GO:00706657	Oral cavity	OSCC	positive regulation of leukocyte proliferation	72/7305	150/18723	1.53e-02	4.95e-02	72
GO:0002181110	Oral cavity	LP	cytoplasmic translation	124/4623	148/18723	5.09e-52	3.19e-48	124
GO:0097193110	Oral cavity	LP	intrinsic apoptotic signaling pathway	146/4623	288/18723	9.76e-22	2.78e-19	146

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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
hsa0401210	Cervix	CC	ErbB signaling pathway	28/1267	85/8465	2.40e-05	1.82e-04	1.08e-04	28
hsa043609	Cervix	CC	Axon guidance	47/1267	182/8465	8.13e-05	5.38e-04	3.18e-04	47
hsa046604	Cervix	CC	T cell receptor signaling pathway	25/1267	104/8465	9.52e-03	2.94e-02	1.74e-02	25
hsa05130110	Cervix	CC	Pathogenic Escherichia coli infection	63/1267	197/8465	9.28e-10	2.00e-08	1.19e-08	63
hsa0401213	Cervix	CC	ErbB signaling pathway	28/1267	85/8465	2.40e-05	1.82e-04	1.08e-04	28
hsa0436012	Cervix	CC	Axon guidance	47/1267	182/8465	8.13e-05	5.38e-04	3.18e-04	47
hsa0466011	Cervix	CC	T cell receptor signaling pathway	25/1267	104/8465	9.52e-03	2.94e-02	1.74e-02	25
hsa0513039	Esophagus	HGIN	Pathogenic Escherichia coli infection	54/1383	197/8465	4.91e-05	6.15e-04	4.89e-04	54
hsa05130115	Esophagus	HGIN	Pathogenic Escherichia coli infection	54/1383	197/8465	4.91e-05	6.15e-04	4.89e-04	54
hsa05130211	Esophagus	ESCC	Pathogenic Escherichia coli infection	142/4205	197/8465	8.21e-11	1.06e-09	5.42e-10	142
hsa0401218	Esophagus	ESCC	ErbB signaling pathway	56/4205	85/8465	1.78e-03	5.24e-03	2.68e-03	56
hsa0436016	Esophagus	ESCC	Axon guidance	108/4205	182/8465	5.13e-03	1.30e-02	6.67e-03	108
hsa046607	Esophagus	ESCC	T cell receptor signaling pathway	63/4205	104/8465	1.60e-02	3.60e-02	1.84e-02	63
hsa05130310	Esophagus	ESCC	Pathogenic Escherichia coli infection	142/4205	197/8465	8.21e-11	1.06e-09	5.42e-10	142
hsa0401219	Esophagus	ESCC	ErbB signaling pathway	56/4205	85/8465	1.78e-03	5.24e-03	2.68e-03	56
hsa0436017	Esophagus	ESCC	Axon guidance	108/4205	182/8465	5.13e-03	1.30e-02	6.67e-03	108
hsa0466013	Esophagus	ESCC	T cell receptor signaling pathway	63/4205	104/8465	1.60e-02	3.60e-02	1.84e-02	63
hsa0513014	Liver	NAFLD	Pathogenic Escherichia coli infection	45/1043	197/8465	2.31e-05	6.88e-04	5.54e-04	45
hsa0513015	Liver	NAFLD	Pathogenic Escherichia coli infection	45/1043	197/8465	2.31e-05	6.88e-04	5.54e-04	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

NCK1

SNV

Missense_Mutation

novel

c.599N>T

p.Pro200Leu

p.P200L

P16333

protein_coding

tolerated(0.06)

benign(0.302)

TCGA-AO-A03O-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

NCK1

SNV

Missense_Mutation

novel

c.809G>A

p.Arg270Lys

p.R270K

P16333

protein_coding

tolerated(0.98)

benign(0.001)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NCK1

SNV

Missense_Mutation

rs749985486

c.773N>T

p.Gly258Val

p.G258V

P16333

protein_coding

deleterious(0.04)

benign(0.011)

TCGA-C5-A3HE-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NCK1

SNV

Missense_Mutation

novel

c.649N>G

p.Met217Val

p.M217V

P16333

protein_coding

deleterious(0.01)

benign(0.086)

TCGA-C5-A905-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NCK1

SNV

Missense_Mutation

c.256N>A

p.Val86Met

p.V86M

P16333

protein_coding

tolerated(0.17)

benign(0.001)

TCGA-DS-A0VN-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NCK1

SNV

Missense_Mutation

c.314N>G

p.Tyr105Cys

p.Y105C

P16333

protein_coding

tolerated(0.07)

possibly_damaging(0.827)

TCGA-IR-A3LC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unspecific

Cisplatin

Complete Response

NCK1

SNV

Missense_Mutation

c.358N>A

p.Glu120Lys

p.E120K

P16333

protein_coding

tolerated(0.21)

benign(0.348)

TCGA-MA-AA41-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NCK1

SNV

Missense_Mutation

c.531N>T

p.Glu177Asp

p.E177D

P16333

protein_coding

tolerated(0.41)

benign(0.001)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

NCK1

SNV

Missense_Mutation

novel

c.1099N>C

p.Gly367Arg

p.G367R

P16333

protein_coding

deleterious(0)

probably_damaging(0.985)

TCGA-A5-A0GG-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

NCK1

SNV

Missense_Mutation

novel

c.616G>A

p.Asp206Asn

p.D206N

P16333

protein_coding

deleterious(0.03)

possibly_damaging(0.456)

TCGA-A5-A1OK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

taxol

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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
4690	NCK1	KINASE		AX-024

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