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:0032526	Oral cavity	OSCC	response to retinoic acid	54/7305	107/18723	1.04e-02	3.54e-02	54
GO:00024441	Oral cavity	OSCC	myeloid leukocyte mediated immunity	50/7305	99/18723	1.31e-02	4.34e-02	50
GO:00313495	Oral cavity	OSCC	positive regulation of defense response	127/7305	278/18723	1.32e-02	4.39e-02	127
GO:00703724	Oral cavity	OSCC	regulation of ERK1 and ERK2 cascade	140/7305	309/18723	1.34e-02	4.46e-02	140
GO:00466517	Oral cavity	OSCC	lymphocyte proliferation	131/7305	288/18723	1.41e-02	4.67e-02	131
GO:00075999	Oral cavity	OSCC	hemostasis	103/7305	222/18723	1.45e-02	4.73e-02	103
GO:00508179	Oral cavity	OSCC	coagulation	103/7305	222/18723	1.45e-02	4.73e-02	103
GO:00706657	Oral cavity	OSCC	positive regulation of leukocyte proliferation	72/7305	150/18723	1.53e-02	4.95e-02	72
GO:0045862110	Oral cavity	LP	positive regulation of proteolysis	165/4623	372/18723	5.40e-17	8.46e-15	165
GO:0052547110	Oral cavity	LP	regulation of peptidase activity	177/4623	461/18723	3.01e-11	2.00e-09	177
GO:0052548110	Oral cavity	LP	regulation of endopeptidase activity	164/4623	432/18723	4.33e-10	2.20e-08	164
GO:0010952110	Oral cavity	LP	positive regulation of peptidase activity	88/4623	197/18723	6.52e-10	3.14e-08	88
GO:005165615	Oral cavity	LP	establishment of organelle localization	147/4623	390/18723	6.01e-09	2.46e-07	147
GO:0010950110	Oral cavity	LP	positive regulation of endopeptidase activity	79/4623	179/18723	9.34e-09	3.62e-07	79
GO:0071496110	Oral cavity	LP	cellular response to external stimulus	124/4623	320/18723	1.44e-08	5.36e-07	124
GO:0051348110	Oral cavity	LP	negative regulation of transferase activity	106/4623	268/18723	4.60e-08	1.61e-06	106
GO:0034605110	Oral cavity	LP	cellular response to heat	37/4623	69/18723	2.35e-07	7.03e-06	37
GO:0010563110	Oral cavity	LP	negative regulation of phosphorus metabolic process	153/4623	442/18723	1.47e-06	3.53e-05	153
GO:0045936110	Oral cavity	LP	negative regulation of phosphate metabolic process	152/4623	441/18723	2.10e-06	4.77e-05	152
GO:0031668110	Oral cavity	LP	cellular response to extracellular stimulus	91/4623	246/18723	1.07e-05	1.94e-04	91

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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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