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: DR1

Gene summary for DR1

Gene summary.

Gene information	Species	Human
	Gene symbol	DR1
	Gene ID	1810
	Gene name	down-regulator of transcription 1
	Gene Alias	NC2
	Cytomap	1p22.1
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q01658

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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
1810	DR1	LZE4T	Human	Esophagus	ESCC	1.67e-11	1.98e-01	0.0811
1810	DR1	LZE5T	Human	Esophagus	ESCC	7.01e-04	1.10e-01	0.0514
1810	DR1	LZE8T	Human	Esophagus	ESCC	1.60e-02	-8.08e-02	0.067
1810	DR1	LZE20T	Human	Esophagus	ESCC	4.18e-07	1.65e-01	0.0662
1810	DR1	LZE22T	Human	Esophagus	ESCC	2.43e-03	2.40e-01	0.068
1810	DR1	LZE24T	Human	Esophagus	ESCC	2.94e-10	4.24e-01	0.0596
1810	DR1	P2T-E	Human	Esophagus	ESCC	7.94e-36	6.94e-01	0.1177
1810	DR1	P4T-E	Human	Esophagus	ESCC	4.76e-23	3.55e-01	0.1323
1810	DR1	P5T-E	Human	Esophagus	ESCC	4.54e-26	6.38e-01	0.1327
1810	DR1	P8T-E	Human	Esophagus	ESCC	1.15e-22	3.52e-01	0.0889
1810	DR1	P9T-E	Human	Esophagus	ESCC	2.00e-16	2.70e-01	0.1131
1810	DR1	P10T-E	Human	Esophagus	ESCC	1.51e-36	7.30e-01	0.116
1810	DR1	P11T-E	Human	Esophagus	ESCC	2.61e-11	5.52e-01	0.1426
1810	DR1	P12T-E	Human	Esophagus	ESCC	1.79e-84	2.02e+00	0.1122
1810	DR1	P15T-E	Human	Esophagus	ESCC	4.18e-26	6.79e-01	0.1149
1810	DR1	P16T-E	Human	Esophagus	ESCC	3.22e-27	2.94e-01	0.1153
1810	DR1	P17T-E	Human	Esophagus	ESCC	3.09e-05	4.32e-01	0.1278
1810	DR1	P19T-E	Human	Esophagus	ESCC	1.27e-06	8.87e-01	0.1662
1810	DR1	P20T-E	Human	Esophagus	ESCC	6.66e-28	7.21e-01	0.1124
1810	DR1	P21T-E	Human	Esophagus	ESCC	1.01e-20	1.98e-01	0.1617

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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
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
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:190290334	Oral cavity	NEOLP	regulation of supramolecular fiber organization	88/2005	383/18723	2.44e-12	4.83e-10	88
GO:000701534	Oral cavity	NEOLP	actin filament organization	94/2005	442/18723	4.49e-11	5.80e-09	94
GO:003009932	Oral cavity	NEOLP	myeloid cell differentiation	83/2005	381/18723	1.79e-10	1.69e-08	83
GO:003297033	Oral cavity	NEOLP	regulation of actin filament-based process	85/2005	397/18723	2.70e-10	2.51e-08	85
GO:003432923	Oral cavity	NEOLP	cell junction assembly	88/2005	420/18723	4.18e-10	3.44e-08	88
GO:190290533	Oral cavity	NEOLP	positive regulation of supramolecular fiber organization	53/2005	209/18723	1.47e-09	1.01e-07	53
GO:003295633	Oral cavity	NEOLP	regulation of actin cytoskeleton organization	77/2005	358/18723	1.51e-09	1.02e-07	77
GO:002260433	Oral cavity	NEOLP	regulation of cell morphogenesis	69/2005	309/18723	2.07e-09	1.29e-07	69
GO:000716333	Oral cavity	NEOLP	establishment or maintenance of cell polarity	53/2005	218/18723	7.21e-09	3.82e-07	53
GO:002241131	Oral cavity	NEOLP	cellular component disassembly	87/2005	443/18723	1.39e-08	6.46e-07	87
GO:000836033	Oral cavity	NEOLP	regulation of cell shape	41/2005	154/18723	2.35e-08	1.03e-06	41
GO:011005333	Oral cavity	NEOLP	regulation of actin filament organization	60/2005	278/18723	8.37e-08	3.17e-06	60
GO:004521625	Oral cavity	NEOLP	cell-cell junction organization	47/2005	200/18723	1.51e-07	5.21e-06	47
GO:005149532	Oral cavity	NEOLP	positive regulation of cytoskeleton organization	50/2005	226/18723	4.47e-07	1.35e-05	50
GO:003253532	Oral cavity	NEOLP	regulation of cellular component size	73/2005	383/18723	6.70e-07	1.93e-05	73
GO:003103224	Oral cavity	NEOLP	actomyosin structure organization	44/2005	196/18723	1.42e-06	3.58e-05	44
GO:000815431	Oral cavity	NEOLP	actin polymerization or depolymerization	47/2005	218/18723	2.11e-06	4.91e-05	47
GO:004269221	Oral cavity	NEOLP	muscle cell differentiation	71/2005	384/18723	2.97e-06	6.76e-05	71
GO:000806432	Oral cavity	NEOLP	regulation of actin polymerization or depolymerization	41/2005	188/18723	6.83e-06	1.36e-04	41
GO:003083232	Oral cavity	NEOLP	regulation of actin filament length	41/2005	189/18723	7.83e-06	1.54e-04	41

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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

DR1

SNV

Missense_Mutation

novel

c.25N>A

p.Asp9Asn

p.D9N

Q01658

protein_coding

deleterious(0)

probably_damaging(0.975)

TCGA-C5-A1MH-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

DR1

SNV

Missense_Mutation

c.145N>A

p.Leu49Ile

p.L49I

Q01658

protein_coding

deleterious(0.02)

probably_damaging(0.92)

TCGA-CA-6715-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

oxaliplatin

DR1

SNV

Missense_Mutation

c.146N>G

p.Leu49Arg

p.L49R

Q01658

protein_coding

deleterious(0)

probably_damaging(0.975)

TCGA-A5-A2K5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

DR1

SNV

Missense_Mutation

c.328N>C

p.Asn110His

p.N110H

Q01658

protein_coding

tolerated(0.08)

benign(0.222)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

DR1

SNV

Missense_Mutation

novel

c.253N>G

p.Ser85Gly

p.S85G

Q01658

protein_coding

tolerated(0.29)

benign(0.04)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

DR1

SNV

Missense_Mutation

c.161N>T

p.Ala54Val

p.A54V

Q01658

protein_coding

deleterious(0.02)

possibly_damaging(0.668)

TCGA-AX-A0J0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

DR1

SNV

Missense_Mutation

novel

c.41C>T

p.Pro14Leu

p.P14L

Q01658

protein_coding

deleterious(0)

possibly_damaging(0.618)

TCGA-AX-A3FT-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

DR1

SNV

Missense_Mutation

rs182894486

c.403G>A

p.Glu135Lys

p.E135K

Q01658

protein_coding

tolerated(0.16)

possibly_damaging(0.522)

TCGA-B5-A0JY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

DR1

SNV

Missense_Mutation

c.472G>A

p.Ala158Thr

p.A158T

Q01658

protein_coding

tolerated(0.38)

probably_damaging(0.956)

TCGA-BK-A0C9-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

DR1

SNV

Missense_Mutation

c.516N>A

p.Asp172Glu

p.D172E

Q01658

protein_coding

tolerated_low_confidence(0.32)

benign(0)

TCGA-D1-A176-01

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

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