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: DBP

Gene summary for DBP

Gene summary.

Gene information	Species	Human
	Gene symbol	DBP
	Gene ID	1628
	Gene name	D-box binding PAR bZIP transcription factor
	Gene Alias	DABP
	Cytomap	19q13.33
	Gene Type	protein-coding
	GO ID	GO:0001889
	UniProtAcc	Q10586

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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
1628	DBP	LZE4T	Human	Esophagus	ESCC	4.74e-04	2.18e-01	0.0811
1628	DBP	LZE5T	Human	Esophagus	ESCC	2.70e-03	2.56e-01	0.0514
1628	DBP	LZE22T	Human	Esophagus	ESCC	3.64e-05	3.39e-01	0.068
1628	DBP	LZE24T	Human	Esophagus	ESCC	1.20e-08	2.35e-01	0.0596
1628	DBP	P1T-E	Human	Esophagus	ESCC	1.56e-05	3.58e-01	0.0875
1628	DBP	P2T-E	Human	Esophagus	ESCC	6.11e-13	2.99e-01	0.1177
1628	DBP	P4T-E	Human	Esophagus	ESCC	1.09e-16	3.45e-01	0.1323
1628	DBP	P5T-E	Human	Esophagus	ESCC	4.95e-06	1.03e-01	0.1327
1628	DBP	P8T-E	Human	Esophagus	ESCC	4.89e-27	5.79e-01	0.0889
1628	DBP	P10T-E	Human	Esophagus	ESCC	9.62e-45	8.11e-01	0.116
1628	DBP	P11T-E	Human	Esophagus	ESCC	6.62e-08	3.52e-01	0.1426
1628	DBP	P12T-E	Human	Esophagus	ESCC	4.84e-31	5.37e-01	0.1122
1628	DBP	P15T-E	Human	Esophagus	ESCC	8.38e-23	4.52e-01	0.1149
1628	DBP	P16T-E	Human	Esophagus	ESCC	1.96e-08	1.74e-01	0.1153
1628	DBP	P20T-E	Human	Esophagus	ESCC	9.53e-09	1.29e-01	0.1124
1628	DBP	P21T-E	Human	Esophagus	ESCC	2.17e-06	1.59e-01	0.1617
1628	DBP	P22T-E	Human	Esophagus	ESCC	4.13e-11	2.93e-01	0.1236
1628	DBP	P23T-E	Human	Esophagus	ESCC	2.31e-19	3.95e-01	0.108
1628	DBP	P24T-E	Human	Esophagus	ESCC	3.86e-04	1.05e-01	0.1287
1628	DBP	P26T-E	Human	Esophagus	ESCC	4.84e-43	8.76e-01	0.1276

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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
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:0016032	Colorectum	AD	viral process	168/3918	415/18723	4.67e-20	3.66e-17	168
GO:0008380	Colorectum	AD	RNA splicing	169/3918	434/18723	3.59e-18	2.04e-15	169
GO:0009896	Colorectum	AD	positive regulation of catabolic process	180/3918	492/18723	4.33e-16	1.94e-13	180
GO:1903311	Colorectum	AD	regulation of mRNA metabolic process	117/3918	288/18723	1.69e-14	4.23e-12	117
GO:0031331	Colorectum	AD	positive regulation of cellular catabolic process	156/3918	427/18723	4.68e-14	1.05e-11	156
GO:0009895	Colorectum	AD	negative regulation of catabolic process	124/3918	320/18723	1.66e-13	3.35e-11	124
GO:1903829	Colorectum	AD	positive regulation of cellular protein localization	110/3918	276/18723	4.58e-13	8.44e-11	110
GO:0031330	Colorectum	AD	negative regulation of cellular catabolic process	104/3918	262/18723	2.66e-12	3.96e-10	104
GO:0072594	Colorectum	AD	establishment of protein localization to organelle	148/3918	422/18723	7.95e-12	1.04e-09	148
GO:0031647	Colorectum	AD	regulation of protein stability	108/3918	298/18723	6.33e-10	5.08e-08	108
GO:0006401	Colorectum	AD	RNA catabolic process	102/3918	278/18723	8.64e-10	6.76e-08	102
GO:1904951	Colorectum	AD	positive regulation of establishment of protein localization	112/3918	319/18723	2.55e-09	1.80e-07	112
GO:0044270	Colorectum	AD	cellular nitrogen compound catabolic process	147/3918	451/18723	3.35e-09	2.23e-07	147
GO:0046700	Colorectum	AD	heterocycle catabolic process	145/3918	445/18723	4.37e-09	2.84e-07	145
GO:0006402	Colorectum	AD	mRNA catabolic process	87/3918	232/18723	4.40e-09	2.84e-07	87
GO:0051222	Colorectum	AD	positive regulation of protein transport	106/3918	303/18723	8.45e-09	5.08e-07	106
GO:0034655	Colorectum	AD	nucleobase-containing compound catabolic process	133/3918	407/18723	1.56e-08	9.12e-07	133
GO:0019439	Colorectum	AD	aromatic compound catabolic process	146/3918	467/18723	7.48e-08	3.84e-06	146
GO:1901361	Colorectum	AD	organic cyclic compound catabolic process	153/3918	495/18723	8.23e-08	4.18e-06	153
GO:0034976	Colorectum	AD	response to endoplasmic reticulum stress	90/3918	256/18723	8.48e-08	4.28e-06	90

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa047105	Esophagus	ESCC	Circadian rhythm	24/4205	34/8465	1.09e-02	2.51e-02	1.29e-02	24
hsa0471012	Esophagus	ESCC	Circadian rhythm	24/4205	34/8465	1.09e-02	2.51e-02	1.29e-02	24

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
DBP	CD8TEXP	Breast	ADJ	HS2ST1,TNFRSF10B,MARCH3, etc.	6.60e-02
DBP	ECM	Breast	IDC	PLTP,SELENOP,CTSF, etc.	2.43e-01
DBP	INCAF	Cervix	CC	TSC22D3,SFRP4,H3-3B, etc.	3.47e-01
DBP	TFH	Liver	Cirrhotic	MIR181A2HG,ZNRF2,NEDD4L, etc.	4.26e-01
DBP	TFH	Liver	HCC	MIR181A2HG,ZNRF2,NEDD4L, etc.	1.95e-01
DBP	BN	Liver	Healthy	MIR181A2HG,ZNRF2,NEDD4L, etc.	3.78e-02

∗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

DBP

insertion

Frame_Shift_Ins

novel

c.557_558insAAGA

p.Ser187ArgfsTer21

p.S187Rfs*21

Q10586

protein_coding

TCGA-AO-A03R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

DBP

insertion

Frame_Shift_Ins

novel

c.556_557insGGCAGGAGGATCTCTTGAGCTCGGGAGTT

p.Thr186ArgfsTer27

p.T186Rfs*27

Q10586

protein_coding

TCGA-AO-A03R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

DBP

insertion

Frame_Shift_Ins

novel

c.829_830insAG

p.Arg277GlnfsTer136

p.R277Qfs*136

Q10586

protein_coding

TCGA-B6-A0I6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DBP

insertion

In_Frame_Ins

novel

c.626_627insTTTTCTCACAGTCAAGCCTGGGCTTCTCCTTGGGAT

p.Pro209_Ala210insPheLeuThrValLysProGlyLeuLeuLeuGlyIle

p.P209_A210insFLTVKPGLLLGI

Q10586

protein_coding

TCGA-BH-A0HY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

taxotere

DBP

SNV

Missense_Mutation

novel

c.4N>A

p.Ala2Thr

p.A2T

Q10586

protein_coding

deleterious_low_confidence(0)

benign(0.014)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DBP

SNV

Missense_Mutation

novel

c.829N>T

p.Arg277Trp

p.R277W

Q10586

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AA-3845-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

DBP

SNV

Missense_Mutation

novel

c.677N>A

p.Arg226Gln

p.R226Q

Q10586

protein_coding

deleterious(0)

probably_damaging(0.924)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

DBP

SNV

Missense_Mutation

novel

c.949C>G

p.Arg317Gly

p.R317G

Q10586

protein_coding

deleterious(0)

possibly_damaging(0.532)

TCGA-AJ-A2QM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

DBP

SNV

Missense_Mutation

novel

c.134N>T

p.Ala45Val

p.A45V

Q10586

protein_coding

deleterious(0.03)

benign(0.006)

TCGA-AP-A0LS-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

DBP

SNV

Missense_Mutation

c.817N>T

p.Arg273Cys

p.R273C

Q10586

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-D1-A167-01

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
1628	DBP	TRANSCRIPTION FACTOR		ALBUMIN	ALBUMIN HUMAN	2331750

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