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: MDFI

Gene summary for MDFI

Gene summary.

Gene information	Species	Human
	Gene symbol	MDFI
	Gene ID	4188
	Gene name	MyoD family inhibitor
	Gene Alias	I-MF
	Cytomap	6p21.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	A0A024RCY2

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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
4188	MDFI	GSM4909281	Human	Breast	IDC	2.90e-55	8.29e-01	0.21
4188	MDFI	GSM4909282	Human	Breast	IDC	5.21e-20	4.08e-01	-0.0288
4188	MDFI	GSM4909285	Human	Breast	IDC	8.44e-52	7.31e-01	0.21
4188	MDFI	GSM4909305	Human	Breast	IDC	9.84e-04	2.39e-01	0.0436
4188	MDFI	GSM4909306	Human	Breast	IDC	6.38e-06	2.77e-01	0.1564
4188	MDFI	GSM4909312	Human	Breast	IDC	1.92e-22	6.23e-01	0.1552
4188	MDFI	brca1	Human	Breast	Precancer	7.51e-03	1.65e-01	-0.0338
4188	MDFI	DCIS2	Human	Breast	DCIS	1.18e-16	7.62e-02	0.0085
4188	MDFI	LZE4T	Human	Esophagus	ESCC	6.13e-10	1.60e-01	0.0811
4188	MDFI	LZE22T	Human	Esophagus	ESCC	1.02e-06	4.37e-01	0.068
4188	MDFI	LZE24T	Human	Esophagus	ESCC	3.62e-08	2.16e-01	0.0596
4188	MDFI	P1T-E	Human	Esophagus	ESCC	2.39e-08	4.54e-01	0.0875
4188	MDFI	P2T-E	Human	Esophagus	ESCC	4.28e-90	1.72e+00	0.1177
4188	MDFI	P4T-E	Human	Esophagus	ESCC	6.77e-34	7.98e-01	0.1323
4188	MDFI	P5T-E	Human	Esophagus	ESCC	3.41e-24	5.27e-01	0.1327
4188	MDFI	P8T-E	Human	Esophagus	ESCC	7.37e-21	1.60e-01	0.0889
4188	MDFI	P9T-E	Human	Esophagus	ESCC	2.78e-09	2.31e-01	0.1131
4188	MDFI	P10T-E	Human	Esophagus	ESCC	2.72e-28	4.77e-01	0.116
4188	MDFI	P11T-E	Human	Esophagus	ESCC	4.20e-15	7.55e-01	0.1426
4188	MDFI	P12T-E	Human	Esophagus	ESCC	5.39e-08	2.57e-03	0.1122

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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:019873825	Thyroid	ATC	cell-cell signaling by wnt	234/6293	446/18723	9.26e-17	8.25e-15	234
GO:0046822112	Thyroid	ATC	regulation of nucleocytoplasmic transport	75/6293	106/18723	5.49e-15	3.62e-13	75
GO:003011125	Thyroid	ATC	regulation of Wnt signaling pathway	177/6293	328/18723	1.83e-14	1.05e-12	177
GO:190018023	Thyroid	ATC	regulation of protein localization to nucleus	87/6293	136/18723	3.94e-13	1.79e-11	87
GO:001908023	Thyroid	ATC	viral gene expression	64/6293	94/18723	8.44e-12	3.16e-10	64
GO:004518532	Thyroid	ATC	maintenance of protein location	64/6293	94/18723	8.44e-12	3.16e-10	64
GO:000170126	Thyroid	ATC	in utero embryonic development	183/6293	367/18723	6.62e-11	2.11e-09	183
GO:001703822	Thyroid	ATC	protein import	110/6293	206/18723	3.49e-09	8.09e-08	110
GO:005079228	Thyroid	ATC	regulation of viral process	90/6293	164/18723	1.61e-08	3.23e-07	90
GO:004852424	Thyroid	ATC	positive regulation of viral process	44/6293	65/18723	2.00e-08	3.93e-07	44
GO:005117018	Thyroid	ATC	import into nucleus	86/6293	159/18723	8.02e-08	1.40e-06	86
GO:190382816	Thyroid	ATC	negative regulation of cellular protein localization	67/6293	117/18723	1.23e-07	2.06e-06	67
GO:000660617	Thyroid	ATC	protein import into nucleus	83/6293	155/18723	2.38e-07	3.70e-06	83
GO:005110027	Thyroid	ATC	negative regulation of binding	86/6293	162/18723	2.41e-07	3.73e-06	86
GO:190458918	Thyroid	ATC	regulation of protein import	41/6293	63/18723	3.19e-07	4.76e-06	41
GO:006145827	Thyroid	ATC	reproductive system development	193/6293	427/18723	3.32e-07	4.92e-06	193
GO:003109826	Thyroid	ATC	stress-activated protein kinase signaling cascade	120/6293	247/18723	7.06e-07	9.46e-06	120
GO:005123532	Thyroid	ATC	maintenance of location	152/6293	327/18723	7.84e-07	1.04e-05	152
GO:004860825	Thyroid	ATC	reproductive structure development	190/6293	424/18723	8.40e-07	1.11e-05	190
GO:005140326	Thyroid	ATC	stress-activated MAPK cascade	115/6293	239/18723	2.17e-06	2.58e-05	115

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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

MDFI

SNV

Missense_Mutation

c.522C>G

p.Cys174Trp

p.C174W

Q99750

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AO-A0J6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

MDFI

insertion

Nonsense_Mutation

novel

c.637_638insTGGGATTACAGGCATGAGCCACTGGGCCCGGCCGACTTCTCTTA

p.Asp213ValfsTer6

p.D213Vfs*6

Q99750

protein_coding

TCGA-A2-A0CU-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

MDFI

SNV

Missense_Mutation

c.500N>A

p.Cys167Tyr

p.C167Y

Q99750

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-CK-4951-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

MDFI

SNV

Missense_Mutation

c.500N>A

p.Cys167Tyr

p.C167Y

Q99750

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-AG-3909-01

Colorectum

rectum adenocarcinoma

Female

>=65

III/IV

Chemotherapy

folinic

MDFI

SNV

Missense_Mutation

rs770572756

c.343N>T

p.Arg115Trp

p.R115W

Q99750

protein_coding

deleterious(0.03)

possibly_damaging(0.528)

TCGA-AJ-A3BG-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

MDFI

SNV

Missense_Mutation

novel

c.446N>G

p.Lys149Arg

p.K149R

Q99750

protein_coding

tolerated(0.17)

benign(0.01)

TCGA-AX-A3G9-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

MDFI

SNV

Missense_Mutation

rs768704952

c.382N>T

p.Arg128Trp

p.R128W

Q99750

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-B5-A11H-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Hormone Therapy

megace

MDFI

SNV

Missense_Mutation

rs753464609

c.170N>T

p.Ala57Val

p.A57V

Q99750

protein_coding

tolerated(0.88)

benign(0.003)

TCGA-B5-A3FC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

MDFI

SNV

Missense_Mutation

rs767995449

c.409N>A

p.Ala137Thr

p.A137T

Q99750

protein_coding

tolerated(0.68)

benign(0.009)

TCGA-D1-A167-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

MDFI

SNV

Missense_Mutation

novel

c.371N>T

p.Pro124Leu

p.P124L

Q99750

protein_coding

deleterious(0)

benign(0.036)

TCGA-EY-A215-01

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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