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: LYN

Gene summary for LYN

Gene summary.

Gene information	Species	Human
	Gene symbol	LYN
	Gene ID	4067
	Gene name	LYN proto-oncogene, Src family tyrosine kinase
	Gene Alias	JTK8
	Cytomap	8q12.1
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	P07948

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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
4067	LYN	CA_HPV_1	Human	Cervix	CC	1.07e-10	3.97e-01	0.0264
4067	LYN	CCI_2	Human	Cervix	CC	4.28e-03	9.41e-01	0.5249
4067	LYN	CCI_3	Human	Cervix	CC	6.57e-04	8.77e-01	0.516
4067	LYN	L1	Human	Cervix	CC	1.26e-04	-3.28e-01	0.0802
4067	LYN	LZE4T	Human	Esophagus	ESCC	2.98e-02	2.81e-02	0.0811
4067	LYN	LZE8T	Human	Esophagus	ESCC	3.77e-03	1.94e-01	0.067
4067	LYN	LZE20T	Human	Esophagus	ESCC	2.22e-04	3.47e-01	0.0662
4067	LYN	LZE22D1	Human	Esophagus	HGIN	9.11e-04	1.29e-01	0.0595
4067	LYN	LZE24T	Human	Esophagus	ESCC	1.99e-06	1.13e-01	0.0596
4067	LYN	LZE21T	Human	Esophagus	ESCC	4.98e-02	2.72e-01	0.0655
4067	LYN	P1T-E	Human	Esophagus	ESCC	7.66e-11	1.20e+00	0.0875
4067	LYN	P4T-E	Human	Esophagus	ESCC	6.61e-05	1.05e-01	0.1323
4067	LYN	P8T-E	Human	Esophagus	ESCC	5.18e-25	5.58e-01	0.0889
4067	LYN	P9T-E	Human	Esophagus	ESCC	3.38e-05	5.03e-02	0.1131
4067	LYN	P11T-E	Human	Esophagus	ESCC	1.62e-02	3.82e-01	0.1426
4067	LYN	P15T-E	Human	Esophagus	ESCC	6.13e-03	2.85e-01	0.1149
4067	LYN	P17T-E	Human	Esophagus	ESCC	3.28e-05	4.24e-01	0.1278
4067	LYN	P21T-E	Human	Esophagus	ESCC	1.59e-24	6.96e-01	0.1617
4067	LYN	P22T-E	Human	Esophagus	ESCC	3.03e-09	7.31e-02	0.1236
4067	LYN	P23T-E	Human	Esophagus	ESCC	2.15e-41	1.54e+00	0.108

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:0001776	Oral cavity	OSCC	leukocyte homeostasis	48/7305	87/18723	1.60e-03	7.62e-03	48
GO:00486784	Oral cavity	OSCC	response to axon injury	46/7305	83/18723	1.76e-03	8.31e-03	46
GO:00380942	Oral cavity	OSCC	Fc-gamma receptor signaling pathway	19/7305	28/18723	1.88e-03	8.84e-03	19
GO:00622076	Oral cavity	OSCC	regulation of pattern recognition receptor signaling pathway	56/7305	105/18723	1.99e-03	9.23e-03	56
GO:00022184	Oral cavity	OSCC	activation of innate immune response	31/7305	52/18723	2.08e-03	9.59e-03	31
GO:00603269	Oral cavity	OSCC	cell chemotaxis	146/7305	310/18723	2.13e-03	9.80e-03	146
GO:0060251	Oral cavity	OSCC	regulation of glial cell proliferation	23/7305	36/18723	2.19e-03	9.95e-03	23
GO:00022243	Oral cavity	OSCC	toll-like receptor signaling pathway	63/7305	121/18723	2.36e-03	1.04e-02	63
GO:190303910	Oral cavity	OSCC	positive regulation of leukocyte cell-cell adhesion	115/7305	239/18723	2.48e-03	1.09e-02	115
GO:00703045	Oral cavity	OSCC	positive regulation of stress-activated protein kinase signaling cascade	66/7305	128/18723	2.58e-03	1.13e-02	66
GO:00716758	Oral cavity	OSCC	regulation of mononuclear cell migration	60/7305	115/18723	2.78e-03	1.21e-02	60
GO:00703735	Oral cavity	OSCC	negative regulation of ERK1 and ERK2 cascade	43/7305	78/18723	2.80e-03	1.22e-02	43
GO:00027646	Oral cavity	OSCC	immune response-regulating signaling pathway	212/7305	468/18723	2.93e-03	1.27e-02	212
GO:00192167	Oral cavity	OSCC	regulation of lipid metabolic process	154/7305	331/18723	3.00e-03	1.30e-02	154
GO:0070227	Oral cavity	OSCC	lymphocyte apoptotic process	40/7305	72/18723	3.21e-03	1.38e-02	40
GO:00024333	Oral cavity	OSCC	immune response-regulating cell surface receptor signaling pathway involved in phagocytosis	18/7305	27/18723	3.34e-03	1.42e-02	18
GO:00380963	Oral cavity	OSCC	Fc-gamma receptor signaling pathway involved in phagocytosis	18/7305	27/18723	3.34e-03	1.42e-02	18
GO:00024312	Oral cavity	OSCC	Fc receptor mediated stimulatory signaling pathway	21/7305	33/18723	3.63e-03	1.51e-02	21
GO:20001061	Oral cavity	OSCC	regulation of leukocyte apoptotic process	44/7305	81/18723	3.66e-03	1.51e-02	44
GO:005087010	Oral cavity	OSCC	positive regulation of T cell activation	104/7305	216/18723	3.76e-03	1.55e-02	104

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0541720	Cervix	CC	Lipid and atherosclerosis	65/1267	215/8465	6.47e-09	1.10e-07	6.52e-08	65
hsa0516720	Cervix	CC	Kaposi sarcoma-associated herpesvirus infection	60/1267	194/8465	9.74e-09	1.58e-07	9.33e-08	60
hsa0516920	Cervix	CC	Epstein-Barr virus infection	57/1267	202/8465	7.30e-07	7.39e-06	4.37e-06	57
hsa0466612	Cervix	CC	Fc gamma R-mediated phagocytosis	31/1267	97/8465	1.78e-05	1.42e-04	8.40e-05	31
hsa051207	Cervix	CC	Epithelial cell signaling in Helicobacter pylori infection	24/1267	70/8465	4.35e-05	3.09e-04	1.83e-04	24
hsa04062	Cervix	CC	Chemokine signaling pathway	43/1267	192/8465	3.60e-03	1.34e-02	7.91e-03	43
hsa046115	Cervix	CC	Platelet activation	28/1267	124/8465	1.50e-02	4.45e-02	2.63e-02	28
hsa05417110	Cervix	CC	Lipid and atherosclerosis	65/1267	215/8465	6.47e-09	1.10e-07	6.52e-08	65
hsa05167110	Cervix	CC	Kaposi sarcoma-associated herpesvirus infection	60/1267	194/8465	9.74e-09	1.58e-07	9.33e-08	60
hsa05169110	Cervix	CC	Epstein-Barr virus infection	57/1267	202/8465	7.30e-07	7.39e-06	4.37e-06	57
hsa0466613	Cervix	CC	Fc gamma R-mediated phagocytosis	31/1267	97/8465	1.78e-05	1.42e-04	8.40e-05	31
hsa0512014	Cervix	CC	Epithelial cell signaling in Helicobacter pylori infection	24/1267	70/8465	4.35e-05	3.09e-04	1.83e-04	24
hsa040621	Cervix	CC	Chemokine signaling pathway	43/1267	192/8465	3.60e-03	1.34e-02	7.91e-03	43
hsa0461113	Cervix	CC	Platelet activation	28/1267	124/8465	1.50e-02	4.45e-02	2.63e-02	28
hsa0516930	Esophagus	HGIN	Epstein-Barr virus infection	55/1383	202/8465	5.13e-05	6.19e-04	4.92e-04	55
hsa0516730	Esophagus	HGIN	Kaposi sarcoma-associated herpesvirus infection	51/1383	194/8465	2.46e-04	2.69e-03	2.14e-03	51
hsa052039	Esophagus	HGIN	Viral carcinogenesis	53/1383	204/8465	2.58e-04	2.71e-03	2.15e-03	53
hsa0541739	Esophagus	HGIN	Lipid and atherosclerosis	51/1383	215/8465	2.95e-03	2.41e-02	1.91e-02	51
hsa05169114	Esophagus	HGIN	Epstein-Barr virus infection	55/1383	202/8465	5.13e-05	6.19e-04	4.92e-04	55
hsa05167114	Esophagus	HGIN	Kaposi sarcoma-associated herpesvirus infection	51/1383	194/8465	2.46e-04	2.69e-03	2.14e-03	51

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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

LYN

SNV

Missense_Mutation

c.475N>A

p.Glu159Lys

p.E159K

P07948

protein_coding

deleterious(0.01)

probably_damaging(0.987)

TCGA-A1-A0SO-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

LYN

SNV

Missense_Mutation

c.627N>T

p.Lys209Asn

p.K209N

P07948

protein_coding

tolerated(0.16)

benign(0.056)

TCGA-A2-A0CT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

LYN

SNV

Missense_Mutation

c.57N>C

p.Leu19Phe

p.L19F

P07948

protein_coding

tolerated(0.72)

benign(0.013)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

LYN

SNV

Missense_Mutation

novel

c.1096N>T

p.Arg366Trp

p.R366W

P07948

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-AC-A2FM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

LYN

SNV

Missense_Mutation

novel

c.1442N>C

p.Lys481Thr

p.K481T

P07948

protein_coding

deleterious(0.01)

benign(0.432)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

LYN

SNV

Missense_Mutation

c.1508N>A

p.Ala503Asp

p.A503D

P07948

protein_coding

deleterious(0)

probably_damaging(0.949)

TCGA-B6-A0I9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

LYN

SNV

Missense_Mutation

c.1252N>A

p.Gly418Arg

p.G418R

P07948

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-E2-A155-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

LYN

SNV

Missense_Mutation

novel

c.905N>C

p.Leu302Pro

p.L302P

P07948

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

LYN

SNV

Missense_Mutation

c.20A>T

p.Lys7Ile

p.K7I

P07948

protein_coding

deleterious(0.01)

possibly_damaging(0.482)

TCGA-DS-A1OC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

gemcitabine

LYN

SNV

Missense_Mutation

c.907G>A

p.Val303Met

p.V303M

P07948

protein_coding

deleterious(0)

probably_damaging(0.945)

TCGA-MA-AA42-01

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
4067	LYN	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, ENZYME, CLINICALLY ACTIONABLE, DRUG RESISTANCE		CYC-116	CYC-116
4067	LYN	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, ENZYME, CLINICALLY ACTIONABLE, DRUG RESISTANCE		ILORASERTIB	ILORASERTIB
4067	LYN	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, ENZYME, CLINICALLY ACTIONABLE, DRUG RESISTANCE		SORAFENIB	SORAFENIB
4067	LYN	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, ENZYME, CLINICALLY ACTIONABLE, DRUG RESISTANCE	inhibitor	178102666
4067	LYN	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, ENZYME, CLINICALLY ACTIONABLE, DRUG RESISTANCE		GW459057A	GW459057A	16890436
4067	LYN	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, ENZYME, CLINICALLY ACTIONABLE, DRUG RESISTANCE	inhibitor	NINTEDANIB	NINTEDANIB
4067	LYN	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, ENZYME, CLINICALLY ACTIONABLE, DRUG RESISTANCE		NILOTINIB	NILOTINIB	18191450
4067	LYN	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, ENZYME, CLINICALLY ACTIONABLE, DRUG RESISTANCE	inhibitor	MASITINIB	MASITINIB
4067	LYN	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, ENZYME, CLINICALLY ACTIONABLE, DRUG RESISTANCE		Bafetinib	BAFETINIB
4067	LYN	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, ENZYME, CLINICALLY ACTIONABLE, DRUG RESISTANCE	inhibitor	178103494	IBRUTINIB

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