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: SRC

Gene summary for SRC

Gene summary.

Gene information	Species	Human
	Gene symbol	SRC
	Gene ID	6714
	Gene name	SRC proto-oncogene, non-receptor tyrosine kinase
	Gene Alias	ASV
	Cytomap	20q11.23
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P12931

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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
6714	SRC	LZE4T	Human	Esophagus	ESCC	4.17e-04	8.87e-02	0.0811
6714	SRC	LZE8T	Human	Esophagus	ESCC	6.35e-03	5.66e-02	0.067
6714	SRC	LZE20T	Human	Esophagus	ESCC	3.88e-06	1.87e-01	0.0662
6714	SRC	LZE22T	Human	Esophagus	ESCC	2.39e-03	1.69e-01	0.068
6714	SRC	LZE24T	Human	Esophagus	ESCC	4.07e-12	3.74e-01	0.0596
6714	SRC	P1T-E	Human	Esophagus	ESCC	1.99e-04	2.78e-01	0.0875
6714	SRC	P2T-E	Human	Esophagus	ESCC	3.86e-10	1.07e-01	0.1177
6714	SRC	P4T-E	Human	Esophagus	ESCC	2.75e-19	1.82e-01	0.1323
6714	SRC	P8T-E	Human	Esophagus	ESCC	3.27e-12	2.30e-01	0.0889
6714	SRC	P9T-E	Human	Esophagus	ESCC	1.69e-09	7.57e-02	0.1131
6714	SRC	P10T-E	Human	Esophagus	ESCC	4.36e-10	1.94e-01	0.116
6714	SRC	P11T-E	Human	Esophagus	ESCC	4.18e-12	3.10e-01	0.1426
6714	SRC	P12T-E	Human	Esophagus	ESCC	2.98e-17	3.51e-01	0.1122
6714	SRC	P15T-E	Human	Esophagus	ESCC	6.55e-13	2.98e-01	0.1149
6714	SRC	P16T-E	Human	Esophagus	ESCC	8.91e-15	2.73e-01	0.1153
6714	SRC	P17T-E	Human	Esophagus	ESCC	6.33e-06	2.31e-01	0.1278
6714	SRC	P20T-E	Human	Esophagus	ESCC	5.91e-17	3.27e-01	0.1124
6714	SRC	P21T-E	Human	Esophagus	ESCC	3.51e-20	4.69e-01	0.1617
6714	SRC	P22T-E	Human	Esophagus	ESCC	6.37e-11	2.23e-01	0.1236
6714	SRC	P23T-E	Human	Esophagus	ESCC	2.79e-14	2.57e-01	0.108

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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

∗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:0051348110	Oral cavity	LP	negative regulation of transferase activity	106/4623	268/18723	4.60e-08	1.61e-06	106
GO:0034599110	Oral cavity	LP	cellular response to oxidative stress	110/4623	288/18723	2.19e-07	6.65e-06	110
GO:000072317	Oral cavity	LP	telomere maintenance	59/4623	131/18723	2.88e-07	8.56e-06	59
GO:0031667110	Oral cavity	LP	response to nutrient levels	165/4623	474/18723	3.87e-07	1.12e-05	165
GO:004339319	Oral cavity	LP	regulation of protein binding	80/4623	196/18723	4.41e-07	1.23e-05	80
GO:001063919	Oral cavity	LP	negative regulation of organelle organization	127/4623	348/18723	5.07e-07	1.40e-05	127
GO:1901654110	Oral cavity	LP	response to ketone	78/4623	194/18723	1.24e-06	3.03e-05	78
GO:0048545110	Oral cavity	LP	response to steroid hormone	122/4623	339/18723	1.91e-06	4.39e-05	122
GO:001648214	Oral cavity	LP	cytosolic transport	69/4623	168/18723	2.03e-06	4.65e-05	69
GO:000038017	Oral cavity	LP	alternative mRNA splicing, via spliceosome	38/4623	77/18723	2.47e-06	5.43e-05	38
GO:2001236110	Oral cavity	LP	regulation of extrinsic apoptotic signaling pathway	63/4623	151/18723	2.98e-06	6.47e-05	63
GO:0048732110	Oral cavity	LP	gland development	149/4623	436/18723	4.51e-06	9.17e-05	149
GO:003010017	Oral cavity	LP	regulation of endocytosis	81/4623	211/18723	6.57e-06	1.29e-04	81
GO:005188116	Oral cavity	LP	regulation of mitochondrial membrane potential	36/4623	74/18723	6.85e-06	1.34e-04	36
GO:0070482110	Oral cavity	LP	response to oxygen levels	122/4623	347/18723	7.10e-06	1.37e-04	122
GO:007189715	Oral cavity	LP	DNA biosynthetic process	71/4623	180/18723	8.04e-06	1.52e-04	71
GO:005105213	Oral cavity	LP	regulation of DNA metabolic process	125/4623	359/18723	9.43e-06	1.75e-04	125
GO:005105415	Oral cavity	LP	positive regulation of DNA metabolic process	77/4623	201/18723	1.20e-05	2.15e-04	77
GO:0045861110	Oral cavity	LP	negative regulation of proteolysis	122/4623	351/18723	1.32e-05	2.34e-04	122
GO:000961215	Oral cavity	LP	response to mechanical stimulus	81/4623	216/18723	1.80e-05	3.09e-04	81

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04144210	Esophagus	ESCC	Endocytosis	186/4205	251/8465	9.74e-16	4.66e-14	2.39e-14	186
hsa05208211	Esophagus	ESCC	Chemical carcinogenesis - reactive oxygen species	168/4205	223/8465	1.83e-15	6.81e-14	3.49e-14	168
hsa05418211	Esophagus	ESCC	Fluid shear stress and atherosclerosis	109/4205	139/8465	2.00e-12	3.72e-11	1.90e-11	109
hsa05131211	Esophagus	ESCC	Shigellosis	176/4205	247/8465	2.27e-12	4.01e-11	2.05e-11	176
hsa05130211	Esophagus	ESCC	Pathogenic Escherichia coli infection	142/4205	197/8465	8.21e-11	1.06e-09	5.42e-10	142
hsa05167211	Esophagus	ESCC	Kaposi sarcoma-associated herpesvirus infection	136/4205	194/8465	4.28e-09	4.22e-08	2.16e-08	136
hsa0513526	Esophagus	ESCC	Yersinia infection	100/4205	137/8465	1.80e-08	1.59e-07	8.12e-08	100
hsa0520529	Esophagus	ESCC	Proteoglycans in cancer	138/4205	205/8465	1.79e-07	1.40e-06	7.15e-07	138
hsa0520325	Esophagus	ESCC	Viral carcinogenesis	137/4205	204/8465	2.47e-07	1.88e-06	9.62e-07	137
hsa05417211	Esophagus	ESCC	Lipid and atherosclerosis	143/4205	215/8465	3.30e-07	2.45e-06	1.26e-06	143
hsa05163210	Esophagus	ESCC	Human cytomegalovirus infection	148/4205	225/8465	5.73e-07	4.00e-06	2.05e-06	148
hsa05100211	Esophagus	ESCC	Bacterial invasion of epithelial cells	59/4205	77/8465	1.05e-06	6.76e-06	3.46e-06	59
hsa0452030	Esophagus	ESCC	Adherens junction	69/4205	93/8465	1.08e-06	6.83e-06	3.50e-06	69
hsa0521910	Esophagus	ESCC	Bladder cancer	35/4205	41/8465	1.91e-06	1.15e-05	5.87e-06	35
hsa051619	Esophagus	ESCC	Hepatitis B	108/4205	162/8465	7.68e-06	4.15e-05	2.12e-05	108
hsa04137210	Esophagus	ESCC	Mitophagy - animal	54/4205	72/8465	9.33e-06	4.96e-05	2.54e-05	54
hsa046259	Esophagus	ESCC	C-type lectin receptor signaling pathway	73/4205	104/8465	1.57e-05	7.98e-05	4.09e-05	73
hsa0512018	Esophagus	ESCC	Epithelial cell signaling in Helicobacter pylori infection	52/4205	70/8465	2.17e-05	1.07e-04	5.47e-05	52
hsa0451020	Esophagus	ESCC	Focal adhesion	127/4205	203/8465	1.25e-04	4.99e-04	2.56e-04	127
hsa0152110	Esophagus	ESCC	EGFR tyrosine kinase inhibitor resistance	55/4205	79/8465	2.44e-04	8.78e-04	4.50e-04	55

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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

SRC

SNV

Missense_Mutation

c.806C>T

p.Ser269Leu

p.S269L

P12931

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

SRC

insertion

Frame_Shift_Ins

novel

c.1176_1177insCTCATCT

p.Ala393LeufsTer25

p.A393Lfs*25

P12931

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

SRC

insertion

Frame_Shift_Ins

novel

c.1177_1178insTGTCTGGGTCCGCTGGGGCCTCTTTC

p.Ala393ValfsTer72

p.A393Vfs*72

P12931

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

SRC

SNV

Missense_Mutation

novel

c.11N>G

p.Asn4Ser

p.N4S

P12931

protein_coding

tolerated_low_confidence(0.97)

benign(0)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SRC

SNV

Missense_Mutation

novel

c.439C>A

p.Gln147Lys

p.Q147K

P12931

protein_coding

deleterious(0.04)

possibly_damaging(0.882)

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

SRC

SNV

Missense_Mutation

c.1571N>T

p.Thr524Met

p.T524M

P12931

protein_coding

deleterious(0.01)

possibly_damaging(0.52)

TCGA-AD-6899-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Unknown

SRC

SNV

Missense_Mutation

c.1489N>A

p.Leu497Ile

p.L497I

P12931

protein_coding

tolerated(1)

probably_damaging(0.993)

TCGA-AD-A5EJ-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

SRC

SNV

Missense_Mutation

novel

c.659N>A

p.Arg220His

p.R220H

P12931

protein_coding

deleterious(0.01)

benign(0.428)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

SRC

SNV

Missense_Mutation

rs533607141

c.812N>A

p.Arg271Gln

p.R271Q

P12931

protein_coding

tolerated(0.53)

benign(0.318)

TCGA-AJ-A3BG-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

SRC

SNV

Missense_Mutation

c.272C>T

p.Ala91Val

p.A91V

P12931

protein_coding

deleterious(0.01)

benign(0.437)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

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
6714	SRC	CLINICALLY ACTIONABLE, KINASE, TYROSINE KINASE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR, ENZYME		CEDIRANIB	CEDIRANIB
6714	SRC	CLINICALLY ACTIONABLE, KINASE, TYROSINE KINASE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR, ENZYME	inhibitor	CHEMBL24828	VANDETANIB
6714	SRC	CLINICALLY ACTIONABLE, KINASE, TYROSINE KINASE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR, ENZYME	inhibitor	CHEMBL3545196	PD-0166285
6714	SRC	CLINICALLY ACTIONABLE, KINASE, TYROSINE KINASE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR, ENZYME		DOVITINIB	DOVITINIB
6714	SRC	CLINICALLY ACTIONABLE, KINASE, TYROSINE KINASE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR, ENZYME		TYRPHOSTIN A9		11112699
6714	SRC	CLINICALLY ACTIONABLE, KINASE, TYROSINE KINASE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR, ENZYME		KX2-361	KX2-361
6714	SRC	CLINICALLY ACTIONABLE, KINASE, TYROSINE KINASE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR, ENZYME		AZD0530	SARACATINIB
6714	SRC	CLINICALLY ACTIONABLE, KINASE, TYROSINE KINASE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR, ENZYME	inhibitor	178102599
6714	SRC	CLINICALLY ACTIONABLE, KINASE, TYROSINE KINASE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR, ENZYME	inhibitor	CHEMBL1421	DASATINIB
6714	SRC	CLINICALLY ACTIONABLE, KINASE, TYROSINE KINASE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR, ENZYME	inhibitor	354702286

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