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: SP1

Gene summary for SP1

Gene summary.

Gene information	Species	Human
	Gene symbol	SP1
	Gene ID	6667
	Gene name	Sp1 transcription factor
	Gene Alias	SP1
	Cytomap	12q13.13
	Gene Type	protein-coding
	GO ID	GO:0001525
	UniProtAcc	P08047

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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
6667	SP1	LZE4T	Human	Esophagus	ESCC	1.58e-05	8.02e-02	0.0811
6667	SP1	LZE7T	Human	Esophagus	ESCC	1.22e-04	2.12e-01	0.0667
6667	SP1	LZE8T	Human	Esophagus	ESCC	1.59e-06	1.11e-01	0.067
6667	SP1	LZE22T	Human	Esophagus	ESCC	1.22e-02	1.00e-01	0.068
6667	SP1	LZE24T	Human	Esophagus	ESCC	6.08e-11	2.26e-01	0.0596
6667	SP1	LZE21T	Human	Esophagus	ESCC	3.76e-03	8.41e-02	0.0655
6667	SP1	LZE6T	Human	Esophagus	ESCC	1.31e-02	6.57e-02	0.0845
6667	SP1	P1T-E	Human	Esophagus	ESCC	1.89e-08	3.88e-01	0.0875
6667	SP1	P2T-E	Human	Esophagus	ESCC	2.59e-25	4.75e-01	0.1177
6667	SP1	P4T-E	Human	Esophagus	ESCC	3.77e-07	1.06e-01	0.1323
6667	SP1	P5T-E	Human	Esophagus	ESCC	1.32e-10	8.41e-02	0.1327
6667	SP1	P8T-E	Human	Esophagus	ESCC	2.91e-24	3.77e-01	0.0889
6667	SP1	P9T-E	Human	Esophagus	ESCC	1.30e-07	1.24e-01	0.1131
6667	SP1	P10T-E	Human	Esophagus	ESCC	7.24e-13	2.20e-01	0.116
6667	SP1	P11T-E	Human	Esophagus	ESCC	2.19e-05	1.00e-01	0.1426
6667	SP1	P12T-E	Human	Esophagus	ESCC	1.74e-11	1.35e-01	0.1122
6667	SP1	P15T-E	Human	Esophagus	ESCC	4.18e-14	2.29e-01	0.1149
6667	SP1	P16T-E	Human	Esophagus	ESCC	1.21e-12	1.46e-01	0.1153
6667	SP1	P17T-E	Human	Esophagus	ESCC	8.00e-05	2.50e-01	0.1278
6667	SP1	P20T-E	Human	Esophagus	ESCC	2.95e-16	1.91e-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
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:004854518	Prostate	BPH	response to steroid hormone	109/3107	339/18723	9.35e-13	8.15e-11	109
GO:190305018	Prostate	BPH	regulation of proteolysis involved in cellular protein catabolic process	80/3107	221/18723	1.20e-12	1.02e-10	80
GO:003133418	Prostate	BPH	positive regulation of protein-containing complex assembly	84/3107	237/18723	1.24e-12	1.04e-10	84
GO:007233118	Prostate	BPH	signal transduction by p53 class mediator	64/3107	163/18723	3.51e-12	2.82e-10	64
GO:003227317	Prostate	BPH	positive regulation of protein polymerization	57/3107	138/18723	4.64e-12	3.68e-10	57
GO:003238610	Prostate	BPH	regulation of intracellular transport	106/3107	337/18723	8.77e-12	6.70e-10	106
GO:006145810	Prostate	BPH	reproductive system development	126/3107	427/18723	1.35e-11	9.95e-10	126
GO:005125818	Prostate	BPH	protein polymerization	96/3107	297/18723	1.52e-11	1.10e-09	96
GO:009719118	Prostate	BPH	extrinsic apoptotic signaling pathway	77/3107	219/18723	1.67e-11	1.19e-09	77
GO:005254718	Prostate	BPH	regulation of peptidase activity	133/3107	461/18723	2.08e-11	1.43e-09	133
GO:003227118	Prostate	BPH	regulation of protein polymerization	80/3107	233/18723	2.67e-11	1.78e-09	80
GO:200123618	Prostate	BPH	regulation of extrinsic apoptotic signaling pathway	59/3107	151/18723	3.07e-11	2.02e-09	59
GO:004860810	Prostate	BPH	reproductive structure development	124/3107	424/18723	3.76e-11	2.43e-09	124
GO:003158910	Prostate	BPH	cell-substrate adhesion	110/3107	363/18723	4.64e-11	2.96e-09	110
GO:003243418	Prostate	BPH	regulation of proteasomal ubiquitin-dependent protein catabolic process	54/3107	134/18723	5.22e-11	3.29e-09	54
GO:004206018	Prostate	BPH	wound healing	123/3107	422/18723	5.74e-11	3.59e-09	123
GO:000030218	Prostate	BPH	response to reactive oxygen species	76/3107	222/18723	9.75e-11	5.92e-09	76
GO:000716316	Prostate	BPH	establishment or maintenance of cell polarity	75/3107	218/18723	9.93e-11	5.97e-09	75
GO:006113618	Prostate	BPH	regulation of proteasomal protein catabolic process	67/3107	187/18723	1.34e-10	7.74e-09	67
GO:015011615	Prostate	BPH	regulation of cell-substrate junction organization	35/3107	71/18723	1.81e-10	1.02e-08	35

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05016210	Esophagus	ESCC	Huntington disease	226/4205	306/8465	1.38e-18	8.72e-17	4.46e-17	226
hsa05415211	Esophagus	ESCC	Diabetic cardiomyopathy	146/4205	203/8465	5.81e-11	7.78e-10	3.99e-10	146
hsa05163210	Esophagus	ESCC	Human cytomegalovirus infection	148/4205	225/8465	5.73e-07	4.00e-06	2.05e-06	148
hsa04137210	Esophagus	ESCC	Mitophagy - animal	54/4205	72/8465	9.33e-06	4.96e-05	2.54e-05	54
hsa0501728	Esophagus	ESCC	Spinocerebellar ataxia	94/4205	143/8465	6.77e-05	2.90e-04	1.48e-04	94
hsa043507	Esophagus	ESCC	TGF-beta signaling pathway	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa052028	Esophagus	ESCC	Transcriptional misregulation in cancer	116/4205	193/8465	2.08e-03	5.95e-03	3.05e-03	116
hsa015227	Esophagus	ESCC	Endocrine resistance	63/4205	98/8465	2.38e-03	6.58e-03	3.37e-03	63
hsa0492816	Esophagus	ESCC	Parathyroid hormone synthesis, secretion and action	66/4205	106/8465	5.86e-03	1.47e-02	7.51e-03	66
hsa052319	Esophagus	ESCC	Choline metabolism in cancer	61/4205	98/8465	7.97e-03	1.92e-02	9.84e-03	61
hsa0501638	Esophagus	ESCC	Huntington disease	226/4205	306/8465	1.38e-18	8.72e-17	4.46e-17	226
hsa0541538	Esophagus	ESCC	Diabetic cardiomyopathy	146/4205	203/8465	5.81e-11	7.78e-10	3.99e-10	146
hsa0516338	Esophagus	ESCC	Human cytomegalovirus infection	148/4205	225/8465	5.73e-07	4.00e-06	2.05e-06	148
hsa0413738	Esophagus	ESCC	Mitophagy - animal	54/4205	72/8465	9.33e-06	4.96e-05	2.54e-05	54
hsa0501736	Esophagus	ESCC	Spinocerebellar ataxia	94/4205	143/8465	6.77e-05	2.90e-04	1.48e-04	94
hsa0435014	Esophagus	ESCC	TGF-beta signaling pathway	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa0520213	Esophagus	ESCC	Transcriptional misregulation in cancer	116/4205	193/8465	2.08e-03	5.95e-03	3.05e-03	116
hsa0152215	Esophagus	ESCC	Endocrine resistance	63/4205	98/8465	2.38e-03	6.58e-03	3.37e-03	63
hsa0492817	Esophagus	ESCC	Parathyroid hormone synthesis, secretion and action	66/4205	106/8465	5.86e-03	1.47e-02	7.51e-03	66
hsa0523114	Esophagus	ESCC	Choline metabolism in cancer	61/4205	98/8465	7.97e-03	1.92e-02	9.84e-03	61

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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
SP1	STM	Thyroid	goiters	PLA2G4A,UACA,AC096733.2, etc.	6.95e-01

∗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

SP1

SNV

Missense_Mutation

rs775622089

c.314A>G

p.Asn105Ser

p.N105S

P08047

protein_coding

deleterious(0.01)

probably_damaging(0.968)

TCGA-AN-A0AR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SP1

SNV

Missense_Mutation

c.49N>T

p.Ile17Phe

p.I17F

P08047

protein_coding

tolerated_low_confidence(0.08)

benign(0.227)

TCGA-AN-A0FJ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

SP1

SNV

Missense_Mutation

c.1262N>T

p.Ser421Leu

p.S421L

P08047

protein_coding

deleterious(0.01)

possibly_damaging(0.587)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SP1

SNV

Missense_Mutation

c.1997N>A

p.Arg666His

p.R666H

P08047

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SP1

SNV

Missense_Mutation

c.202T>C

p.Cys68Arg

p.C68R

P08047

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-EW-A1IZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

SP1

SNV

Missense_Mutation

novel

c.407N>G

p.Ser136Cys

p.S136C

P08047

protein_coding

deleterious(0.01)

possibly_damaging(0.648)

TCGA-GM-A3XL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

SP1

insertion

Nonsense_Mutation

novel

c.1611_1612insCCAGTTTTATTTTGATTGTTTTCTTTGGAA

p.Leu537_Gly538insProValLeuPheTerLeuPheSerLeuGlu

p.L537_G538insPVLF*LFSLE

P08047

protein_coding

TCGA-A7-A0DA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SP1

SNV

Missense_Mutation

c.2022N>C

p.Gln674His

p.Q674H

P08047

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

SP1

SNV

Missense_Mutation

c.2022N>C

p.Gln674His

p.Q674H

P08047

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-C5-A3HL-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

SP1

SNV

Missense_Mutation

novel

c.2009N>T

p.Ser670Leu

p.S670L

P08047

protein_coding

deleterious(0)

probably_damaging(0.982)

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

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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
6667	SP1	TRANSCRIPTION FACTOR		Terameprocol	TERAMEPROCOL
6667	SP1	TRANSCRIPTION FACTOR		metformin	METFORMIN	24853734,29352482

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