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: DDR2

Gene summary for DDR2

Gene summary.

Gene information	Species	Human
	Gene symbol	DDR2
	Gene ID	4921
	Gene name	discoidin domain receptor tyrosine kinase 2
	Gene Alias	MIG20a
	Cytomap	1q23.3
	Gene Type	protein-coding
	GO ID	GO:0001503
	UniProtAcc	A0A024R906

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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
4921	DDR2	P2T-E	Human	Esophagus	ESCC	1.05e-32	6.61e-01	0.1177
4921	DDR2	P4T-E	Human	Esophagus	ESCC	2.11e-02	2.05e-01	0.1323
4921	DDR2	P9T-E	Human	Esophagus	ESCC	3.61e-02	2.71e-01	0.1131
4921	DDR2	P11T-E	Human	Esophagus	ESCC	2.77e-04	2.17e-01	0.1426
4921	DDR2	P16T-E	Human	Esophagus	ESCC	1.00e-21	5.63e-01	0.1153
4921	DDR2	P44T-E	Human	Esophagus	ESCC	7.37e-04	3.46e-01	0.1096
4921	DDR2	P56T-E	Human	Esophagus	ESCC	5.16e-07	1.10e+00	0.1613
4921	DDR2	P76T-E	Human	Esophagus	ESCC	1.98e-06	2.43e-01	0.1207
4921	DDR2	P130T-E	Human	Esophagus	ESCC	9.11e-18	4.88e-01	0.1676
4921	DDR2	ATC11	Human	Thyroid	ATC	8.60e-08	1.16e+00	0.3386
4921	DDR2	ATC12	Human	Thyroid	ATC	5.88e-57	1.05e+00	0.34
4921	DDR2	ATC13	Human	Thyroid	ATC	6.70e-71	1.44e+00	0.34
4921	DDR2	ATC2	Human	Thyroid	ATC	1.14e-12	1.51e+00	0.34
4921	DDR2	ATC3	Human	Thyroid	ATC	2.54e-19	1.27e+00	0.338
4921	DDR2	ATC4	Human	Thyroid	ATC	5.19e-59	1.28e+00	0.34
4921	DDR2	ATC5	Human	Thyroid	ATC	2.22e-85	1.54e+00	0.34

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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
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗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:0022411111	Esophagus	ESCC	cellular component disassembly	305/8552	443/18723	1.94e-23	4.57e-21	305
GO:00510908	Esophagus	ESCC	regulation of DNA-binding transcription factor activity	252/8552	440/18723	5.22e-07	6.97e-06	252
GO:000164918	Esophagus	ESCC	osteoblast differentiation	140/8552	229/18723	1.63e-06	1.95e-05	140
GO:004677710	Esophagus	ESCC	protein autophosphorylation	138/8552	227/18723	2.98e-06	3.38e-05	138
GO:000150317	Esophagus	ESCC	ossification	232/8552	408/18723	3.00e-06	3.40e-05	232
GO:00510918	Esophagus	ESCC	positive regulation of DNA-binding transcription factor activity	155/8552	260/18723	3.83e-06	4.14e-05	155
GO:004814414	Esophagus	ESCC	fibroblast proliferation	57/8552	81/18723	5.83e-06	6.03e-05	57
GO:004586018	Esophagus	ESCC	positive regulation of protein kinase activity	219/8552	386/18723	6.91e-06	6.97e-05	219
GO:003367420	Esophagus	ESCC	positive regulation of kinase activity	260/8552	467/18723	7.26e-06	7.22e-05	260
GO:004814514	Esophagus	ESCC	regulation of fibroblast proliferation	56/8552	80/18723	9.08e-06	8.71e-05	56
GO:00301984	Esophagus	ESCC	extracellular matrix organization	171/8552	301/18723	6.08e-05	4.67e-04	171
GO:00430624	Esophagus	ESCC	extracellular structure organization	171/8552	302/18723	7.73e-05	5.76e-04	171
GO:00452294	Esophagus	ESCC	external encapsulating structure organization	172/8552	304/18723	7.80e-05	5.80e-04	172
GO:19030553	Esophagus	ESCC	positive regulation of extracellular matrix organization	20/8552	25/18723	4.81e-04	2.69e-03	20
GO:000166720	Esophagus	ESCC	ameboidal-type cell migration	250/8552	475/18723	1.22e-03	5.97e-03	250
GO:00182124	Esophagus	ESCC	peptidyl-tyrosine modification	202/8552	378/18723	1.34e-03	6.39e-03	202
GO:00301993	Esophagus	ESCC	collagen fibril organization	40/8552	61/18723	1.35e-03	6.44e-03	40
GO:00107619	Esophagus	ESCC	fibroblast migration	32/8552	47/18723	1.59e-03	7.43e-03	32
GO:00181084	Esophagus	ESCC	peptidyl-tyrosine phosphorylation	200/8552	375/18723	1.60e-03	7.45e-03	200
GO:00456675	Esophagus	ESCC	regulation of osteoblast differentiation	77/8552	132/18723	2.28e-03	1.00e-02	77

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

DDR2

SNV

Missense_Mutation

c.1848N>C

p.Lys616Asn

p.K616N

Q16832

protein_coding

deleterious(0.02)

probably_damaging(0.994)

TCGA-A7-A13F-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

DDR2

SNV

Missense_Mutation

novel

c.2537A>C

p.His846Pro

p.H846P

Q16832

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-A8-A0A6-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

epirubicin

DDR2

SNV

Missense_Mutation

novel

c.329A>G

p.His110Arg

p.H110R

Q16832

protein_coding

tolerated(0.11)

benign(0.178)

TCGA-AQ-A54N-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DDR2

SNV

Missense_Mutation

c.1219N>C

p.Ala407Pro

p.A407P

Q16832

protein_coding

deleterious(0)

possibly_damaging(0.899)

TCGA-AR-A0TQ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

DDR2

SNV

Missense_Mutation

novel

c.2249C>T

p.Pro750Leu

p.P750L

Q16832

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-AR-A0TU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Doxorubicin

DDR2

SNV

Missense_Mutation

c.995G>A

p.Arg332Gln

p.R332Q

Q16832

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-AR-A252-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

DDR2

SNV

Missense_Mutation

c.368N>T

p.Ser123Ile

p.S123I

Q16832

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A0AW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

DDR2

SNV

Missense_Mutation

c.1012C>T

p.Leu338Phe

p.L338F

Q16832

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-BH-A0B0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

DDR2

SNV

Missense_Mutation

c.1083G>C

p.Glu361Asp

p.E361D

Q16832

protein_coding

deleterious(0)

probably_damaging(0.983)

TCGA-BH-A0E1-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

DDR2

SNV

Missense_Mutation

c.526N>A

p.Val176Met

p.V176M

Q16832

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-C8-A274-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

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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
4921	DDR2	KINASE, TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, TYROSINE KINASE		ERLOTINIB	ERLOTINIB	22328973
4921	DDR2	KINASE, TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, TYROSINE KINASE		US9156852, 105
4921	DDR2	KINASE, TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, TYROSINE KINASE	inhibitor	178102337	SORAFENIB
4921	DDR2	KINASE, TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, TYROSINE KINASE	inhibitor	384403668
4921	DDR2	KINASE, TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, TYROSINE KINASE		SARACATINIB	SARACATINIB	26191369
4921	DDR2	KINASE, TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, TYROSINE KINASE	inhibitor	381118815
4921	DDR2	KINASE, TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, TYROSINE KINASE	inhibitor	178102324	NILOTINIB
4921	DDR2	KINASE, TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, TYROSINE KINASE		US9156852, 38
4921	DDR2	KINASE, TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, TYROSINE KINASE		US9156852, 1
4921	DDR2	KINASE, TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, TYROSINE KINASE		DASATINIB	DASATINIB	22328973,23932362,18938156

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