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: SAFB2

Gene summary for SAFB2

Gene summary.

Gene information	Species	Human
	Gene symbol	SAFB2
	Gene ID	9667
	Gene name	scaffold attachment factor B2
	Gene Alias	SAFB2
	Cytomap	19p13.3
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q14151

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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
9667	SAFB2	LZE4T	Human	Esophagus	ESCC	9.90e-10	3.58e-01	0.0811
9667	SAFB2	LZE7T	Human	Esophagus	ESCC	2.14e-17	7.93e-01	0.0667
9667	SAFB2	LZE8T	Human	Esophagus	ESCC	1.45e-08	2.05e-01	0.067
9667	SAFB2	LZE20T	Human	Esophagus	ESCC	3.30e-04	1.70e-01	0.0662
9667	SAFB2	LZE24T	Human	Esophagus	ESCC	1.41e-17	4.40e-01	0.0596
9667	SAFB2	LZE6T	Human	Esophagus	ESCC	1.39e-02	2.22e-01	0.0845
9667	SAFB2	P1T-E	Human	Esophagus	ESCC	2.09e-08	5.10e-01	0.0875
9667	SAFB2	P2T-E	Human	Esophagus	ESCC	1.13e-23	3.84e-01	0.1177
9667	SAFB2	P4T-E	Human	Esophagus	ESCC	6.14e-31	7.59e-01	0.1323
9667	SAFB2	P5T-E	Human	Esophagus	ESCC	6.56e-18	5.60e-01	0.1327
9667	SAFB2	P8T-E	Human	Esophagus	ESCC	1.73e-21	5.31e-01	0.0889
9667	SAFB2	P9T-E	Human	Esophagus	ESCC	5.26e-17	5.47e-01	0.1131
9667	SAFB2	P10T-E	Human	Esophagus	ESCC	2.74e-32	7.33e-01	0.116
9667	SAFB2	P11T-E	Human	Esophagus	ESCC	4.62e-11	5.20e-01	0.1426
9667	SAFB2	P12T-E	Human	Esophagus	ESCC	4.61e-28	6.12e-01	0.1122
9667	SAFB2	P15T-E	Human	Esophagus	ESCC	2.06e-23	5.34e-01	0.1149
9667	SAFB2	P16T-E	Human	Esophagus	ESCC	5.61e-17	3.46e-01	0.1153
9667	SAFB2	P17T-E	Human	Esophagus	ESCC	8.62e-09	2.83e-01	0.1278
9667	SAFB2	P19T-E	Human	Esophagus	ESCC	2.52e-06	5.65e-01	0.1662
9667	SAFB2	P20T-E	Human	Esophagus	ESCC	2.27e-22	5.26e-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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:1903311110	Esophagus	ESCC	regulation of mRNA metabolic process	210/8552	288/18723	3.25e-21	5.56e-19	210
GO:0050684110	Esophagus	ESCC	regulation of mRNA processing	109/8552	137/18723	3.51e-16	2.59e-14	109
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:00331438	Esophagus	ESCC	regulation of intracellular steroid hormone receptor signaling pathway	50/8552	74/18723	1.16e-04	8.04e-04	50
GO:003052118	Esophagus	ESCC	androgen receptor signaling pathway	31/8552	44/18723	7.70e-04	3.99e-03	31
GO:000975516	Esophagus	ESCC	hormone-mediated signaling pathway	106/8552	190/18723	3.13e-03	1.30e-02	106
GO:00607655	Esophagus	ESCC	regulation of androgen receptor signaling pathway	20/8552	28/18723	5.23e-03	1.97e-02	20
GO:190331111	Liver	Cirrhotic	regulation of mRNA metabolic process	140/4634	288/18723	1.07e-18	1.91e-16	140
GO:005068411	Liver	Cirrhotic	regulation of mRNA processing	81/4634	137/18723	1.05e-17	1.60e-15	81
GO:004854512	Liver	Cirrhotic	response to steroid hormone	146/4634	339/18723	7.87e-14	6.76e-12	146
GO:007138312	Liver	Cirrhotic	cellular response to steroid hormone stimulus	90/4634	204/18723	1.04e-09	4.70e-08	90
GO:003052212	Liver	Cirrhotic	intracellular receptor signaling pathway	105/4634	265/18723	5.44e-08	1.69e-06	105
GO:004340111	Liver	Cirrhotic	steroid hormone mediated signaling pathway	58/4634	136/18723	3.44e-06	5.95e-05	58
GO:003051811	Liver	Cirrhotic	intracellular steroid hormone receptor signaling pathway	50/4634	116/18723	1.11e-05	1.59e-04	50

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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

SAFB2

SNV

Missense_Mutation

novel

c.530N>A

p.Pro177His

p.P177H

Q14151

protein_coding

tolerated(0.43)

possibly_damaging(0.473)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

SAFB2

SNV

Missense_Mutation

rs777512759

c.2360N>T

p.Ser787Leu

p.S787L

Q14151

protein_coding

deleterious(0)

benign(0.343)

TCGA-A2-A0CL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

SAFB2

SNV

Missense_Mutation

c.2426N>A

p.Gly809Glu

p.G809E

Q14151

protein_coding

deleterious(0.02)

benign(0.381)

TCGA-AN-A0AT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SAFB2

SNV

Missense_Mutation

novel

c.254C>T

p.Ser85Leu

p.S85L

Q14151

protein_coding

deleterious(0.04)

benign(0.001)

TCGA-D8-A3Z6-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphane

SAFB2

SNV

Missense_Mutation

c.1508N>G

p.Glu503Gly

p.E503G

Q14151

protein_coding

deleterious(0.02)

possibly_damaging(0.553)

TCGA-E2-A1LH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SAFB2

SNV

Missense_Mutation

novel

c.221T>C

p.Ile74Thr

p.I74T

Q14151

protein_coding

deleterious(0.01)

benign(0.119)

TCGA-E9-A5FK-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

SAFB2

SNV

Missense_Mutation

c.1802N>T

p.Arg601Leu

p.R601L

Q14151

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-GM-A2DL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

SAFB2

SNV

Missense_Mutation

novel

c.1375N>A

p.Asp459Asn

p.D459N

Q14151

protein_coding

deleterious(0)

benign(0.168)

TCGA-GM-A3NW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

SAFB2

SNV

Missense_Mutation

novel

c.2824N>T

p.His942Tyr

p.H942Y

Q14151

protein_coding

deleterious_low_confidence(0)

benign(0.255)

TCGA-OL-A5RW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SAFB2

insertion

Nonsense_Mutation

novel

c.1489_1490insTTCAAGTGATTCTCCTACTTCAGCCTCCCAAGTAACTGGGACT

p.Glu497ValfsTer12

p.E497Vfs*12

Q14151

protein_coding

TCGA-A2-A0T2-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

xeloda

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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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