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: LCK

Gene summary for LCK

Gene summary.

Gene information	Species	Human
	Gene symbol	LCK
	Gene ID	3932
	Gene name	LCK proto-oncogene, Src family tyrosine kinase
	Gene Alias	IMD22
	Cytomap	1p35.2
	Gene Type	protein-coding
	GO ID	GO:0001775
	UniProtAcc	A0A0S2Z3Y8

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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
3932	LCK	LZE4T	Human	Esophagus	ESCC	5.68e-07	3.24e-01	0.0811
3932	LCK	LZE7T	Human	Esophagus	ESCC	6.11e-12	7.35e-01	0.0667
3932	LCK	LZE8T	Human	Esophagus	ESCC	1.65e-04	2.94e-01	0.067
3932	LCK	LZE6T	Human	Esophagus	ESCC	2.19e-23	1.01e+00	0.0845
3932	LCK	P74T-E	Human	Esophagus	ESCC	5.47e-21	5.05e-01	0.1479
3932	LCK	P82T-E	Human	Esophagus	ESCC	4.14e-03	2.42e-01	0.1072
3932	LCK	P130T-E	Human	Esophagus	ESCC	2.27e-21	5.00e-01	0.1676
3932	LCK	C04	Human	Oral cavity	OSCC	2.83e-02	1.33e-01	0.2633
3932	LCK	C21	Human	Oral cavity	OSCC	1.77e-20	6.06e-01	0.2678
3932	LCK	C30	Human	Oral cavity	OSCC	6.35e-09	3.46e-01	0.3055
3932	LCK	C38	Human	Oral cavity	OSCC	5.01e-10	9.00e-01	0.172
3932	LCK	C46	Human	Oral cavity	OSCC	1.86e-13	1.46e-01	0.1673
3932	LCK	C51	Human	Oral cavity	OSCC	1.89e-05	1.47e-01	0.2674
3932	LCK	C09	Human	Oral cavity	OSCC	2.05e-02	7.16e-02	0.1431

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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
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:0097193111	Esophagus	ESCC	intrinsic apoptotic signaling pathway	222/8552	288/18723	5.87e-28	2.02e-25	222
GO:2001233111	Esophagus	ESCC	regulation of apoptotic signaling pathway	256/8552	356/18723	4.11e-24	1.04e-21	256
GO:0045862111	Esophagus	ESCC	positive regulation of proteolysis	256/8552	372/18723	7.88e-20	9.43e-18	256
GO:2001242111	Esophagus	ESCC	regulation of intrinsic apoptotic signaling pathway	128/8552	164/18723	1.75e-17	1.50e-15	128
GO:2000116111	Esophagus	ESCC	regulation of cysteine-type endopeptidase activity	158/8552	235/18723	1.67e-11	5.90e-10	158
GO:0043281111	Esophagus	ESCC	regulation of cysteine-type endopeptidase activity involved in apoptotic process	143/8552	209/18723	2.12e-11	7.31e-10	143
GO:2001235110	Esophagus	ESCC	positive regulation of apoptotic signaling pathway	92/8552	126/18723	3.91e-10	1.05e-08	92
GO:0010952111	Esophagus	ESCC	positive regulation of peptidase activity	133/8552	197/18723	4.31e-10	1.14e-08	133
GO:0052547111	Esophagus	ESCC	regulation of peptidase activity	275/8552	461/18723	7.54e-10	1.88e-08	275
GO:001631110	Esophagus	ESCC	dephosphorylation	251/8552	417/18723	1.26e-09	2.99e-08	251
GO:000647018	Esophagus	ESCC	protein dephosphorylation	177/8552	281/18723	3.13e-09	6.72e-08	177
GO:0051235110	Esophagus	ESCC	maintenance of location	200/8552	327/18723	1.01e-08	2.02e-07	200
GO:0052548111	Esophagus	ESCC	regulation of endopeptidase activity	253/8552	432/18723	3.68e-08	6.78e-07	253
GO:004578527	Esophagus	ESCC	positive regulation of cell adhesion	255/8552	437/18723	5.07e-08	9.11e-07	255
GO:0010950111	Esophagus	ESCC	positive regulation of endopeptidase activity	116/8552	179/18723	1.77e-07	2.79e-06	116
GO:004206027	Esophagus	ESCC	wound healing	243/8552	422/18723	4.62e-07	6.25e-06	243
GO:0043280110	Esophagus	ESCC	positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	84/8552	129/18723	6.38e-06	6.55e-05	84
GO:2001056110	Esophagus	ESCC	positive regulation of cysteine-type endopeptidase activity	94/8552	148/18723	8.87e-06	8.59e-05	94
GO:200124417	Esophagus	ESCC	positive regulation of intrinsic apoptotic signaling pathway	43/8552	58/18723	9.86e-06	9.37e-05	43
GO:000691915	Esophagus	ESCC	activation of cysteine-type endopeptidase activity involved in apoptotic process	54/8552	78/18723	2.17e-05	1.87e-04	54

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05166211	Esophagus	ESCC	Human T-cell leukemia virus 1 infection	164/4205	222/8465	8.13e-14	2.09e-12	1.07e-12	164
hsa0513526	Esophagus	ESCC	Yersinia infection	100/4205	137/8465	1.80e-08	1.59e-07	8.12e-08	100
hsa040645	Esophagus	ESCC	NF-kappa B signaling pathway	67/4205	104/8465	1.62e-03	4.89e-03	2.50e-03	67
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
hsa05166310	Esophagus	ESCC	Human T-cell leukemia virus 1 infection	164/4205	222/8465	8.13e-14	2.09e-12	1.07e-12	164
hsa05135111	Esophagus	ESCC	Yersinia infection	100/4205	137/8465	1.80e-08	1.59e-07	8.12e-08	100
hsa0406412	Esophagus	ESCC	NF-kappa B signaling pathway	67/4205	104/8465	1.62e-03	4.89e-03	2.50e-03	67
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
hsa0516630	Oral cavity	OSCC	Human T-cell leukemia virus 1 infection	150/3704	222/8465	3.68e-13	7.26e-12	3.70e-12	150
hsa0513520	Oral cavity	OSCC	Yersinia infection	94/3704	137/8465	2.85e-09	3.08e-08	1.57e-08	94
hsa040644	Oral cavity	OSCC	NF-kappa B signaling pathway	67/3704	104/8465	1.57e-05	6.75e-05	3.44e-05	67
hsa046606	Oral cavity	OSCC	T cell receptor signaling pathway	67/3704	104/8465	1.57e-05	6.75e-05	3.44e-05	67
hsa05235	Oral cavity	OSCC	PD-L1 expression and PD-1 checkpoint pathway in cancer	56/3704	89/8465	1.97e-04	6.55e-04	3.33e-04	56
hsa046598	Oral cavity	OSCC	Th17 cell differentiation	65/3704	108/8465	4.02e-04	1.25e-03	6.35e-04	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
LCK	CD8 receptor	LCK_CD8A_CD8B1	LCK	Breast	ADJ
LCK	CD8 receptor	LCK_CD8A_CD8B1	LCK	Breast	DCIS
LCK	CD8 receptor	LCK_CD8A_CD8B1	LCK	Breast	Healthy
LCK	CD8 receptor	LCK_CD8A_CD8B1	LCK	Breast	IDC
LCK	CD8 receptor	LCK_CD8A_CD8B1	LCK	Breast	Precancer
LCK	CD8 receptor	LCK_CD8A_CD8B1	LCK	Cervix	ADJ
LCK	CD8 receptor	LCK_CD8A_CD8B1	LCK	Cervix	CC
LCK	CD8 receptor	LCK_CD8A_CD8B1	LCK	Cervix	Healthy
LCK	CD8 receptor	LCK_CD8A_CD8B1	LCK	Cervix	Precancer
LCK	CD8 receptor	LCK_CD8A_CD8B1	LCK	CRC	AD
LCK	CD8 receptor	LCK_CD8A_CD8B1	LCK	CRC	ADJ
LCK	CD8 receptor	LCK_CD8A_CD8B1	LCK	CRC	MSI-H
LCK	CD8 receptor	LCK_CD8A_CD8B1	LCK	CRC	MSS
LCK	CD8 receptor	LCK_CD8A_CD8B1	LCK	CRC	SER
LCK	CD8 receptor	LCK_CD8A_CD8B1	LCK	Endometrium	ADJ
LCK	CD8 receptor	LCK_CD8A_CD8B1	LCK	Endometrium	AEH
LCK	CD8 receptor	LCK_CD8A_CD8B1	LCK	Endometrium	EEC
LCK	CD8 receptor	LCK_CD8A_CD8B1	LCK	GC	ADJ
LCK	CD8 receptor	LCK_CD8A_CD8B1	LCK	HNSCC	ADJ
LCK	CD8 receptor	LCK_CD8A_CD8B1	LCK	HNSCC	Healthy

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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

LCK

SNV

Missense_Mutation

c.876N>C

p.Met292Ile

p.M292I

P06239

protein_coding

deleterious(0)

possibly_damaging(0.875)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

LCK

SNV

Missense_Mutation

c.1419N>A

p.Met473Ile

p.M473I

P06239

protein_coding

tolerated(0.07)

benign(0.334)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

LCK

SNV

Missense_Mutation

c.1062N>A

p.Phe354Leu

p.F354L

P06239

protein_coding

deleterious(0)

benign(0.043)

TCGA-E9-A1RB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

methotrexate

LCK

SNV

Missense_Mutation

novel

c.469G>A

p.Glu157Lys

p.E157K

P06239

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-VS-A958-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

LCK

SNV

Missense_Mutation

novel

c.821N>A

p.Ser274Asn

p.S274N

P06239

protein_coding

tolerated(0.15)

benign(0)

TCGA-VS-A9UI-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

LCK

SNV

Missense_Mutation

c.1077T>A

p.Asn359Lys

p.N359K

P06239

protein_coding

deleterious(0.02)

probably_damaging(0.943)

TCGA-A6-2681-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

LCK

SNV

Missense_Mutation

novel

c.905G>A

p.Arg302Gln

p.R302Q

P06239

protein_coding

tolerated(0.77)

possibly_damaging(0.901)

TCGA-AA-3949-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

LCK

SNV

Missense_Mutation

rs749760246

c.665N>A

p.Arg222His

p.R222H

P06239

protein_coding

tolerated(0.34)

benign(0.001)

TCGA-AA-3984-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

LCK

SNV

Missense_Mutation

c.695C>T

p.Pro232Leu

p.P232L

P06239

protein_coding

deleterious(0.05)

possibly_damaging(0.775)

TCGA-CM-6680-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

LCK

SNV

Missense_Mutation

novel

c.497C>T

p.Ser166Leu

p.S166L

P06239

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<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
3932	LCK	KINASE, ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TYROSINE KINASE	inhibitor	315661265
3932	LCK	KINASE, ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TYROSINE KINASE	inhibitor	CHEMBL1201733	PAZOPANIB HYDROCHLORIDE
3932	LCK	KINASE, ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TYROSINE KINASE	inhibitor	249565748
3932	LCK	KINASE, ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TYROSINE KINASE		CENISERTIB	CENISERTIB
3932	LCK	KINASE, ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TYROSINE KINASE	inhibitor	249565866
3932	LCK	KINASE, ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TYROSINE KINASE		TCMDC-125758	CHEMBL546797
3932	LCK	KINASE, ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TYROSINE KINASE	inhibitor	223366064	SARACATINIB
3932	LCK	KINASE, ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TYROSINE KINASE		TRIDOLGOSIR	TRIDOLGOSIR	17897956
3932	LCK	KINASE, ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TYROSINE KINASE		SB-220025	SB-220025
3932	LCK	KINASE, ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TYROSINE KINASE		AZAKENPAULLONE	AZAKENPAULLONE

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