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: TMF1

Gene summary for TMF1

Gene summary.

Gene information	Species	Human
	Gene symbol	TMF1
	Gene ID	7110
	Gene name	TATA element modulatory factor 1
	Gene Alias	ARA160
	Cytomap	3p14.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	A0A024R370

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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
7110	TMF1	LZE4T	Human	Esophagus	ESCC	1.68e-17	4.69e-01	0.0811
7110	TMF1	LZE5T	Human	Esophagus	ESCC	6.23e-05	4.06e-01	0.0514
7110	TMF1	LZE7T	Human	Esophagus	ESCC	4.58e-04	1.58e-01	0.0667
7110	TMF1	LZE24T	Human	Esophagus	ESCC	1.11e-23	6.70e-01	0.0596
7110	TMF1	LZE21T	Human	Esophagus	ESCC	1.05e-05	2.99e-01	0.0655
7110	TMF1	LZE6T	Human	Esophagus	ESCC	9.62e-08	2.02e-01	0.0845
7110	TMF1	P1T-E	Human	Esophagus	ESCC	1.15e-05	3.86e-01	0.0875
7110	TMF1	P2T-E	Human	Esophagus	ESCC	1.53e-37	7.55e-01	0.1177
7110	TMF1	P4T-E	Human	Esophagus	ESCC	6.67e-28	7.12e-01	0.1323
7110	TMF1	P5T-E	Human	Esophagus	ESCC	1.35e-10	2.34e-01	0.1327
7110	TMF1	P8T-E	Human	Esophagus	ESCC	7.14e-19	3.63e-01	0.0889
7110	TMF1	P9T-E	Human	Esophagus	ESCC	6.56e-13	3.43e-01	0.1131
7110	TMF1	P10T-E	Human	Esophagus	ESCC	3.33e-19	4.20e-01	0.116
7110	TMF1	P11T-E	Human	Esophagus	ESCC	3.42e-13	5.21e-01	0.1426
7110	TMF1	P12T-E	Human	Esophagus	ESCC	6.70e-16	4.41e-01	0.1122
7110	TMF1	P15T-E	Human	Esophagus	ESCC	8.86e-15	2.87e-01	0.1149
7110	TMF1	P16T-E	Human	Esophagus	ESCC	2.80e-20	4.70e-01	0.1153
7110	TMF1	P17T-E	Human	Esophagus	ESCC	3.44e-05	3.61e-01	0.1278
7110	TMF1	P19T-E	Human	Esophagus	ESCC	9.11e-05	6.59e-01	0.1662
7110	TMF1	P20T-E	Human	Esophagus	ESCC	2.77e-07	2.38e-01	0.1124

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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
Prostate		BPH: Benign Prostatic Hyperplasia
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:0010498111	Esophagus	ESCC	proteasomal protein catabolic process	369/8552	490/18723	1.13e-41	1.80e-38	369
GO:0042176111	Esophagus	ESCC	regulation of protein catabolic process	280/8552	391/18723	8.65e-26	2.39e-23	280
GO:1903362111	Esophagus	ESCC	regulation of cellular protein catabolic process	188/8552	255/18723	5.12e-20	6.62e-18	188
GO:001605014	Esophagus	ESCC	vesicle organization	211/8552	300/18723	2.85e-18	2.87e-16	211
GO:1903050111	Esophagus	ESCC	regulation of proteolysis involved in cellular protein catabolic process	163/8552	221/18723	1.44e-17	1.27e-15	163
GO:0061136111	Esophagus	ESCC	regulation of proteasomal protein catabolic process	142/8552	187/18723	2.40e-17	2.00e-15	142
GO:000699713	Esophagus	ESCC	nucleus organization	96/8552	133/18723	4.66e-10	1.21e-08	96
GO:0030522110	Esophagus	ESCC	intracellular receptor signaling pathway	170/8552	265/18723	8.58e-10	2.09e-08	170
GO:0048545111	Esophagus	ESCC	response to steroid hormone	204/8552	339/18723	4.47e-08	8.11e-07	204
GO:0061458110	Esophagus	ESCC	reproductive system development	247/8552	427/18723	2.24e-07	3.42e-06	247
GO:004860818	Esophagus	ESCC	reproductive structure development	245/8552	424/18723	2.82e-07	4.14e-06	245
GO:0071383110	Esophagus	ESCC	cellular response to steroid hormone stimulus	127/8552	204/18723	1.26e-06	1.55e-05	127
GO:003051819	Esophagus	ESCC	intracellular steroid hormone receptor signaling pathway	76/8552	116/18723	1.25e-05	1.15e-04	76
GO:004340119	Esophagus	ESCC	steroid hormone mediated signaling pathway	87/8552	136/18723	1.25e-05	1.15e-04	87
GO:003052118	Esophagus	ESCC	androgen receptor signaling pathway	31/8552	44/18723	7.70e-04	3.99e-03	31
GO:000181916	Esophagus	ESCC	positive regulation of cytokine production	244/8552	467/18723	2.29e-03	1.01e-02	244
GO:000975516	Esophagus	ESCC	hormone-mediated signaling pathway	106/8552	190/18723	3.13e-03	1.30e-02	106
GO:001049812	Liver	Cirrhotic	proteasomal protein catabolic process	216/4634	490/18723	2.52e-21	9.29e-19	216
GO:004217612	Liver	Cirrhotic	regulation of protein catabolic process	181/4634	391/18723	7.94e-21	2.77e-18	181
GO:190336212	Liver	Cirrhotic	regulation of cellular protein catabolic process	124/4634	255/18723	9.85e-17	1.26e-14	124

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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

TMF1

SNV

Missense_Mutation

novel

c.467N>A

p.Ser156Tyr

p.S156Y

P82094

protein_coding

deleterious_low_confidence(0.01)

benign(0.044)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

TMF1

SNV

Missense_Mutation

novel

c.1513N>G

p.Gln505Glu

p.Q505E

P82094

protein_coding

deleterious(0.02)

benign(0.214)

TCGA-A7-A4SA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

TMF1

SNV

Missense_Mutation

rs764372262

c.356N>T

p.Pro119Leu

p.P119L

P82094

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.895)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TMF1

SNV

Missense_Mutation

rs760281565

c.1961N>A

p.Arg654Gln

p.R654Q

P82094

protein_coding

deleterious(0.02)

probably_damaging(0.973)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TMF1

SNV

Missense_Mutation

c.1117N>A

p.Ala373Thr

p.A373T

P82094

protein_coding

tolerated_low_confidence(0.54)

benign(0)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

TMF1

SNV

Missense_Mutation

c.437N>G

p.Glu146Gly

p.E146G

P82094

protein_coding

tolerated_low_confidence(0.05)

benign(0.05)

TCGA-E2-A1B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Adriamycin

TMF1

insertion

Nonsense_Mutation

novel

c.228_229insGGAGTGTAAGTGAAATCAATTCAGATGAT

p.Ser77GlyfsTer3

p.S77Gfs*3

P82094

protein_coding

TCGA-A2-A0EO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

TMF1

insertion

Frame_Shift_Ins

novel

c.638_639insAACAGCTCCCTCTTTTGACTGTGCTAGGATGCACCACG

p.Ser214ThrfsTer25

p.S214Tfs*25

P82094

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

TMF1

deletion

Frame_Shift_Del

novel

c.2611delN

p.Glu871LysfsTer3

p.E871Kfs*3

P82094

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

TMF1

SNV

Missense_Mutation

c.2382G>T

p.Lys794Asn

p.K794N

P82094

protein_coding

deleterious(0)

probably_damaging(0.972)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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