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: TF

Gene summary for TF

Gene summary.

Gene information	Species	Human
	Gene symbol	TF
	Gene ID	7018
	Gene name	transferrin
	Gene Alias	HEL-S-71p
	Cytomap	3q22.1
	Gene Type	protein-coding
	GO ID	GO:0000041
	UniProtAcc	A0PJA6

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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
7018	TF	P8T-E	Human	Esophagus	ESCC	1.25e-10	4.06e-01	0.0889
7018	TF	P10T-E	Human	Esophagus	ESCC	1.42e-06	-5.41e-02	0.116
7018	TF	P16T-E	Human	Esophagus	ESCC	1.60e-16	2.50e-01	0.1153
7018	TF	P22T-E	Human	Esophagus	ESCC	2.40e-03	-8.78e-02	0.1236
7018	TF	P57T-E	Human	Esophagus	ESCC	9.24e-21	1.12e+00	0.0926
7018	TF	P74T-E	Human	Esophagus	ESCC	2.85e-03	1.43e-01	0.1479
7018	TF	P76T-E	Human	Esophagus	ESCC	5.67e-12	8.38e-01	0.1207
7018	TF	P128T-E	Human	Esophagus	ESCC	5.02e-19	1.31e+00	0.1241
7018	TF	NAFLD1	Human	Liver	NAFLD	1.33e-14	1.52e+00	-0.04
7018	TF	S43	Human	Liver	Cirrhotic	1.96e-06	4.81e-01	-0.0187
7018	TF	HCC1_Meng	Human	Liver	HCC	7.28e-77	1.16e+00	0.0246
7018	TF	HCC2_Meng	Human	Liver	HCC	6.25e-19	-6.79e-01	0.0107
7018	TF	cirrhotic1	Human	Liver	Cirrhotic	3.69e-15	-1.70e-01	0.0202
7018	TF	cirrhotic2	Human	Liver	Cirrhotic	1.67e-15	-1.87e-01	0.0201
7018	TF	cirrhotic3	Human	Liver	Cirrhotic	2.61e-02	-4.09e-01	0.0215
7018	TF	HCC1	Human	Liver	HCC	7.61e-40	8.09e+00	0.5336
7018	TF	HCC2	Human	Liver	HCC	6.48e-53	8.08e+00	0.5341
7018	TF	HCC5	Human	Liver	HCC	3.83e-07	4.78e+00	0.4932
7018	TF	Pt13.a	Human	Liver	HCC	1.44e-27	2.57e-01	0.021
7018	TF	Pt13.b	Human	Liver	HCC	8.21e-34	3.51e-02	0.0251

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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

∗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:00226139	Breast	Precancer	ribonucleoprotein complex biogenesis	79/1080	463/18723	2.11e-18	1.03e-15	79
GO:00971939	Breast	Precancer	intrinsic apoptotic signaling pathway	59/1080	288/18723	8.07e-18	3.60e-15	59
GO:20012339	Breast	Precancer	regulation of apoptotic signaling pathway	65/1080	356/18723	7.70e-17	3.17e-14	65
GO:00069799	Breast	Precancer	response to oxidative stress	70/1080	446/18723	1.59e-14	4.26e-12	70
GO:00525479	Breast	Precancer	regulation of peptidase activity	71/1080	461/18723	2.72e-14	6.94e-12	71
GO:00525489	Breast	Precancer	regulation of endopeptidase activity	67/1080	432/18723	1.06e-13	2.36e-11	67
GO:00422549	Breast	Precancer	ribosome biogenesis	52/1080	299/18723	7.35e-13	1.51e-10	52
GO:00064138	Breast	Precancer	translational initiation	30/1080	118/18723	3.23e-12	5.58e-10	30
GO:00064179	Breast	Precancer	regulation of translation	67/1080	468/18723	4.71e-12	7.64e-10	67
GO:20001169	Breast	Precancer	regulation of cysteine-type endopeptidase activity	43/1080	235/18723	1.30e-11	1.83e-09	43
GO:00621979	Breast	Precancer	cellular response to chemical stress	51/1080	337/18723	2.40e-10	2.34e-08	51
GO:00160329	Breast	Precancer	viral process	58/1080	415/18723	3.42e-10	3.16e-08	58
GO:00422749	Breast	Precancer	ribosomal small subunit biogenesis	21/1080	73/18723	4.84e-10	4.39e-08	21
GO:00190589	Breast	Precancer	viral life cycle	47/1080	317/18723	2.42e-09	1.99e-07	47
GO:00458619	Breast	Precancer	negative regulation of proteolysis	50/1080	351/18723	2.99e-09	2.39e-07	50
GO:00069869	Breast	Precancer	response to unfolded protein	28/1080	137/18723	3.81e-09	3.00e-07	28
GO:00709979	Breast	Precancer	neuron death	50/1080	361/18723	7.75e-09	5.70e-07	50
GO:00514029	Breast	Precancer	neuron apoptotic process	38/1080	246/18723	2.68e-08	1.75e-06	38
GO:00345999	Breast	Precancer	cellular response to oxidative stress	42/1080	288/18723	2.78e-08	1.79e-06	42
GO:00359669	Breast	Precancer	response to topologically incorrect protein	29/1080	159/18723	3.00e-08	1.89e-06	29

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0406629	Esophagus	ESCC	HIF-1 signaling pathway	75/4205	109/8465	3.66e-05	1.68e-04	8.60e-05	75
hsa043507	Esophagus	ESCC	TGF-beta signaling pathway	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa04066113	Esophagus	ESCC	HIF-1 signaling pathway	75/4205	109/8465	3.66e-05	1.68e-04	8.60e-05	75
hsa0435014	Esophagus	ESCC	TGF-beta signaling pathway	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa0421621	Liver	Cirrhotic	Ferroptosis	23/2530	41/8465	4.09e-04	2.57e-03	1.58e-03	23
hsa0406612	Liver	Cirrhotic	HIF-1 signaling pathway	46/2530	109/8465	4.00e-03	1.59e-02	9.78e-03	46
hsa0421631	Liver	Cirrhotic	Ferroptosis	23/2530	41/8465	4.09e-04	2.57e-03	1.58e-03	23
hsa0406613	Liver	Cirrhotic	HIF-1 signaling pathway	46/2530	109/8465	4.00e-03	1.59e-02	9.78e-03	46
hsa0421641	Liver	HCC	Ferroptosis	33/4020	41/8465	1.42e-05	9.88e-05	5.50e-05	33
hsa0406622	Liver	HCC	HIF-1 signaling pathway	70/4020	109/8465	2.96e-04	1.36e-03	7.57e-04	70
hsa0421651	Liver	HCC	Ferroptosis	33/4020	41/8465	1.42e-05	9.88e-05	5.50e-05	33
hsa0406632	Liver	HCC	HIF-1 signaling pathway	70/4020	109/8465	2.96e-04	1.36e-03	7.57e-04	70

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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

SNV

Missense_Mutation

c.1906N>T

p.Gly636Cys

p.G636C

P02787

protein_coding

deleterious(0.01)

possibly_damaging(0.767)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

SNV

Missense_Mutation

novel

c.693N>T

p.Glu231Asp

p.E231D

P02787

protein_coding

tolerated(0.09)

benign(0.138)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

c.1009N>C

p.Glu337Gln

p.E337Q

P02787

protein_coding

tolerated(0.24)

benign(0.03)

TCGA-AN-A0XW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

SNV

Missense_Mutation

c.1565N>C

p.Leu522Pro

p.L522P

P02787

protein_coding

tolerated(0.35)

benign(0)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SNV

Missense_Mutation

novel

c.1816N>C

p.Val606Leu

p.V606L

P02787

protein_coding

deleterious(0)

probably_damaging(0.979)

TCGA-B6-A0RG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SNV

Missense_Mutation

novel

c.1073G>T

p.Cys358Phe

p.C358F

P02787

protein_coding

deleterious(0.05)

benign(0.097)

TCGA-BH-A0BJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SNV

Missense_Mutation

novel

c.161N>T

p.Pro54Leu

p.P54L

P02787

protein_coding

tolerated(0.06)

possibly_damaging(0.843)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SNV

Missense_Mutation

c.1907N>T

p.Gly636Val

p.G636V

P02787

protein_coding

tolerated(0.05)

benign(0.375)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

c.493C>G

p.Leu165Val

p.L165V

P02787

protein_coding

tolerated(0.45)

benign(0.035)

TCGA-EW-A1J5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

insertion

Frame_Shift_Ins

novel

c.2011_2012insCCTCTGGGGGAACAACCACTCA

p.Gly671AlafsTer17

p.G671Afs*17

P02787

protein_coding

TCGA-A8-A07Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unspecific

Exemestane

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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
7018	TF	CELL SURFACE, DRUGGABLE GENOME		adalimumab	ADALIMUMAB	27115882
7018	TF	CELL SURFACE, DRUGGABLE GENOME		Ademetionine	ADEMETIONINE
7018	TF	CELL SURFACE, DRUGGABLE GENOME		CALAA-01
7018	TF	CELL SURFACE, DRUGGABLE GENOME		PF-06763809
7018	TF	CELL SURFACE, DRUGGABLE GENOME		EP-2167

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