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: SREBF1

Gene summary for SREBF1

Gene summary.

Gene information	Species	Human
	Gene symbol	SREBF1
	Gene ID	6720
	Gene name	sterol regulatory element binding transcription factor 1
	Gene Alias	HMD
	Cytomap	17p11.2
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	P36956

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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
6720	SREBF1	GSM4909298	Human	Breast	IDC	1.39e-02	2.30e-01	0.1551
6720	SREBF1	GSM4909301	Human	Breast	IDC	1.56e-05	4.14e-01	0.1577
6720	SREBF1	GSM4909302	Human	Breast	IDC	1.52e-10	5.34e-01	0.1545
6720	SREBF1	GSM4909304	Human	Breast	IDC	2.76e-20	6.36e-01	0.1636
6720	SREBF1	GSM4909311	Human	Breast	IDC	7.52e-04	3.48e-02	0.1534
6720	SREBF1	GSM4909317	Human	Breast	IDC	3.52e-09	4.64e-01	0.1355
6720	SREBF1	GSM4909319	Human	Breast	IDC	7.03e-11	4.37e-02	0.1563
6720	SREBF1	M1	Human	Breast	IDC	2.50e-07	4.62e-01	0.1577
6720	SREBF1	NCCBC11	Human	Breast	DCIS	6.94e-07	6.67e-01	0.1232
6720	SREBF1	NCCBC14	Human	Breast	DCIS	1.79e-02	5.22e-02	0.2021
6720	SREBF1	DCIS2	Human	Breast	DCIS	1.55e-51	2.79e-01	0.0085
6720	SREBF1	CCI_2	Human	Cervix	CC	3.58e-09	1.03e+00	0.5249
6720	SREBF1	CCI_3	Human	Cervix	CC	4.06e-05	8.66e-01	0.516
6720	SREBF1	sample3	Human	Cervix	CC	2.05e-04	2.01e-01	0.1387
6720	SREBF1	T3	Human	Cervix	CC	7.49e-04	1.66e-01	0.1389
6720	SREBF1	LZE2T	Human	Esophagus	ESCC	4.20e-04	8.00e-01	0.082
6720	SREBF1	LZE7T	Human	Esophagus	ESCC	4.02e-06	2.07e-01	0.0667
6720	SREBF1	LZE20T	Human	Esophagus	ESCC	1.02e-07	1.47e-01	0.0662
6720	SREBF1	LZE21D1	Human	Esophagus	HGIN	2.84e-03	1.70e-01	0.0632
6720	SREBF1	LZE22T	Human	Esophagus	ESCC	5.21e-05	6.02e-01	0.068

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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
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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:003052222	Liver	HCC	intracellular receptor signaling pathway	171/7958	265/18723	3.00e-13	1.61e-11	171
GO:003286921	Liver	HCC	cellular response to insulin stimulus	137/7958	203/18723	4.69e-13	2.44e-11	137
GO:004343422	Liver	HCC	response to peptide hormone	247/7958	414/18723	9.55e-13	4.77e-11	247
GO:003166722	Liver	HCC	response to nutrient levels	276/7958	474/18723	2.30e-12	1.08e-10	276
GO:004854522	Liver	HCC	response to steroid hormone	206/7958	339/18723	6.81e-12	2.92e-10	206
GO:000042211	Liver	HCC	autophagy of mitochondrion	64/7958	81/18723	1.96e-11	7.72e-10	64
GO:006172611	Liver	HCC	mitochondrion disassembly	64/7958	81/18723	1.96e-11	7.72e-10	64
GO:007137521	Liver	HCC	cellular response to peptide hormone stimulus	179/7958	290/18723	2.54e-11	9.88e-10	179
GO:000606621	Liver	HCC	alcohol metabolic process	208/7958	353/18723	2.80e-10	9.50e-09	208
GO:190165321	Liver	HCC	cellular response to peptide	211/7958	359/18723	2.86e-10	9.63e-09	211
GO:19026522	Liver	HCC	secondary alcohol metabolic process	100/7958	147/18723	3.26e-10	1.09e-08	100
GO:007149622	Liver	HCC	cellular response to external stimulus	191/7958	320/18723	3.40e-10	1.13e-08	191
GO:00082032	Liver	HCC	cholesterol metabolic process	94/7958	137/18723	5.39e-10	1.72e-08	94
GO:00082022	Liver	HCC	steroid metabolic process	188/7958	319/18723	1.96e-09	5.63e-08	188
GO:00161252	Liver	HCC	sterol metabolic process	101/7958	152/18723	1.99e-09	5.63e-08	101
GO:001082112	Liver	HCC	regulation of mitochondrion organization	96/7958	144/18723	3.82e-09	1.02e-07	96
GO:003166812	Liver	HCC	cellular response to extracellular stimulus	149/7958	246/18723	7.35e-09	1.86e-07	149
GO:190353311	Liver	HCC	regulation of protein targeting	60/7958	81/18723	7.70e-09	1.94e-07	60
GO:190374711	Liver	HCC	regulation of establishment of protein localization to mitochondrion	41/7958	50/18723	1.14e-08	2.83e-07	41
GO:003105621	Liver	HCC	regulation of histone modification	99/7958	152/18723	1.40e-08	3.40e-07	99

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0493243	Breast	DCIS	Non-alcoholic fatty liver disease	49/846	155/8465	5.87e-14	1.35e-12	9.97e-13	49
hsa0493253	Breast	DCIS	Non-alcoholic fatty liver disease	49/846	155/8465	5.87e-14	1.35e-12	9.97e-13	49
hsa0493230	Esophagus	HGIN	Non-alcoholic fatty liver disease	66/1383	155/8465	5.21e-15	1.21e-13	9.64e-14	66
hsa04932113	Esophagus	HGIN	Non-alcoholic fatty liver disease	66/1383	155/8465	5.21e-15	1.21e-13	9.64e-14	66
hsa04932210	Esophagus	ESCC	Non-alcoholic fatty liver disease	122/4205	155/8465	5.69e-14	1.59e-12	8.14e-13	122
hsa0415210	Esophagus	ESCC	AMPK signaling pathway	80/4205	121/8465	1.73e-04	6.67e-04	3.42e-04	80
hsa049109	Esophagus	ESCC	Insulin signaling pathway	89/4205	137/8465	1.97e-04	7.32e-04	3.75e-04	89
hsa049318	Esophagus	ESCC	Insulin resistance	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa0493238	Esophagus	ESCC	Non-alcoholic fatty liver disease	122/4205	155/8465	5.69e-14	1.59e-12	8.14e-13	122
hsa0415213	Esophagus	ESCC	AMPK signaling pathway	80/4205	121/8465	1.73e-04	6.67e-04	3.42e-04	80
hsa0491014	Esophagus	ESCC	Insulin signaling pathway	89/4205	137/8465	1.97e-04	7.32e-04	3.75e-04	89
hsa0493113	Esophagus	ESCC	Insulin resistance	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa0493242	Liver	HCC	Non-alcoholic fatty liver disease	124/4020	155/8465	4.54e-17	2.54e-15	1.41e-15	124
hsa0491041	Liver	HCC	Insulin signaling pathway	95/4020	137/8465	1.53e-07	1.97e-06	1.10e-06	95
hsa0493121	Liver	HCC	Insulin resistance	77/4020	108/8465	3.89e-07	4.46e-06	2.48e-06	77
hsa049362	Liver	HCC	Alcoholic liver disease	89/4020	142/8465	1.73e-04	8.53e-04	4.75e-04	89
hsa0415241	Liver	HCC	AMPK signaling pathway	77/4020	121/8465	2.32e-04	1.11e-03	6.18e-04	77
hsa0493252	Liver	HCC	Non-alcoholic fatty liver disease	124/4020	155/8465	4.54e-17	2.54e-15	1.41e-15	124
hsa0491051	Liver	HCC	Insulin signaling pathway	95/4020	137/8465	1.53e-07	1.97e-06	1.10e-06	95
hsa0493131	Liver	HCC	Insulin resistance	77/4020	108/8465	3.89e-07	4.46e-06	2.48e-06	77

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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
SREBF1	MLUM	Breast	IDC	SCD,FASN,MUC1, etc.	5.53e-01
SREBF1	KER	Esophagus	ESCC	MT-ND4,SCD,MT-CO2, etc.	3.66e-01
SREBF1	CLUB	Lung	IAC	SFTPD,MVP,AQP5, etc.	2.38e-01
SREBF1	cDC	Lung	ADJ	NMB,WDR59,ZNF701, etc.	4.18e-02
SREBF1	LUM	Prostate	ADJ	SCD,SIM2,FASN, etc.	6.71e-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

SREBF1

SNV

Missense_Mutation

c.2306G>A

p.Arg769His

p.R769H

P36956

protein_coding

deleterious(0.04)

probably_damaging(0.96)

TCGA-A8-A07G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

SREBF1

SNV

Missense_Mutation

c.1247N>C

p.Ser416Thr

p.S416T

P36956

protein_coding

tolerated(0.35)

benign(0.015)

TCGA-D8-A1JD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SREBF1

insertion

In_Frame_Ins

novel

c.1439_1440insTGGCAG

p.Ser480_Gly481dup

p.S480_G481dup

P36956

protein_coding

TCGA-E2-A1IF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SREBF1

SNV

Missense_Mutation

c.3266N>A

p.Arg1089His

p.R1089H

P36956

protein_coding

tolerated(0.55)

probably_damaging(0.999)

TCGA-DG-A2KK-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

SREBF1

SNV

Missense_Mutation

c.571N>T

p.Pro191Ser

p.P191S

P36956

protein_coding

tolerated(0.17)

probably_damaging(0.991)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

SREBF1

SNV

Missense_Mutation

c.316N>G

p.Pro106Ala

p.P106A

P36956

protein_coding

tolerated(0.29)

benign(0.143)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

SREBF1

SNV

Missense_Mutation

novel

c.1348N>A

p.Glu450Lys

p.E450K

P36956

protein_coding

tolerated(0.11)

probably_damaging(0.995)

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

SREBF1

SNV

Missense_Mutation

c.1846N>T

p.Arg616Cys

p.R616C

P36956

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-EK-A2RB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SREBF1

SNV

Missense_Mutation

rs868055320

c.3168N>T

p.Gln1056His

p.Q1056H

P36956

protein_coding

tolerated(0.35)

benign(0.07)

TCGA-VS-A94X-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SREBF1

SNV

Missense_Mutation

novel

c.1040N>T

p.Ser347Phe

p.S347F

P36956

protein_coding

tolerated(0.67)

possibly_damaging(0.7)

TCGA-VS-A94X-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
6720	SREBF1	NUCLEAR HORMONE RECEPTOR, TRANSCRIPTION FACTOR		fluvastatin	FLUVASTATIN
6720	SREBF1	NUCLEAR HORMONE RECEPTOR, TRANSCRIPTION FACTOR		hmg coa reductase inhibitors		24329191
6720	SREBF1	NUCLEAR HORMONE RECEPTOR, TRANSCRIPTION FACTOR		INSULIN	INSULIN	10627507,12576518,14594997
6720	SREBF1	NUCLEAR HORMONE RECEPTOR, TRANSCRIPTION FACTOR		NEUROTROPHIC FACTOR		12788519

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