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: FN1

Gene summary for FN1

Gene summary.

Gene information	Species	Human
	Gene symbol	FN1
	Gene ID	2335
	Gene name	fibronectin 1
	Gene Alias	CIG
	Cytomap	2q35
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	B7ZLE5

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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
2335	FN1	GSM4909281	Human	Breast	IDC	1.26e-02	2.49e-01	0.21
2335	FN1	GSM4909287	Human	Breast	IDC	3.77e-02	2.33e-01	0.2057
2335	FN1	GSM4909295	Human	Breast	IDC	3.02e-10	5.92e-01	0.0898
2335	FN1	GSM4909302	Human	Breast	IDC	2.28e-46	9.23e-01	0.1545
2335	FN1	GSM4909307	Human	Breast	IDC	3.08e-07	4.56e-01	0.1569
2335	FN1	GSM4909309	Human	Breast	IDC	2.29e-02	2.64e-01	0.0483
2335	FN1	GSM4909317	Human	Breast	IDC	2.42e-02	2.00e-01	0.1355
2335	FN1	M2	Human	Breast	IDC	8.50e-08	6.55e-01	0.21
2335	FN1	P2	Human	Breast	IDC	7.87e-08	5.15e-01	0.21
2335	FN1	HTA11_866_3004761011	Human	Colorectum	AD	1.80e-02	1.24e+00	0.096
2335	FN1	HTA11_99999973899_84307	Human	Colorectum	MSS	7.00e-04	1.12e+00	0.2585
2335	FN1	HTA11_99999974143_84620	Human	Colorectum	MSS	2.83e-09	1.84e+00	0.3005
2335	FN1	F007	Human	Colorectum	FAP	1.05e-03	-2.53e-01	0.1176
2335	FN1	A001-C-207	Human	Colorectum	FAP	6.53e-06	-2.53e-01	0.1278
2335	FN1	A002-C-201	Human	Colorectum	FAP	4.40e-09	-2.53e-01	0.0324
2335	FN1	A002-C-203	Human	Colorectum	FAP	2.00e-05	-2.47e-01	0.2786
2335	FN1	A001-C-119	Human	Colorectum	FAP	6.20e-23	1.12e+00	-0.1557
2335	FN1	A002-C-021	Human	Colorectum	FAP	1.07e-02	3.83e-01	0.1171
2335	FN1	A002-C-205	Human	Colorectum	FAP	8.74e-09	-2.53e-01	-0.1236
2335	FN1	A014-C-108	Human	Colorectum	FAP	2.28e-02	-2.19e-01	-0.124

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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
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:00432549	Breast	Precancer	regulation of protein-containing complex assembly	50/1080	428/18723	1.63e-06	5.97e-05	50
GO:00508219	Breast	Precancer	protein stabilization	29/1080	191/18723	1.67e-06	6.08e-05	29
GO:00313349	Breast	Precancer	positive regulation of protein-containing complex assembly	33/1080	237/18723	2.39e-06	8.21e-05	33
GO:00316479	Breast	Precancer	regulation of protein stability	38/1080	298/18723	3.73e-06	1.19e-04	38
GO:00106348	Breast	Precancer	positive regulation of epithelial cell migration	25/1080	176/18723	2.75e-05	6.21e-04	25
GO:19029059	Breast	Precancer	positive regulation of supramolecular fiber organization	28/1080	209/18723	2.79e-05	6.28e-04	28
GO:00106319	Breast	Precancer	epithelial cell migration	40/1080	357/18723	4.57e-05	9.71e-04	40
GO:19029039	Breast	Precancer	regulation of supramolecular fiber organization	42/1080	383/18723	4.92e-05	1.04e-03	42
GO:00901329	Breast	Precancer	epithelium migration	40/1080	360/18723	5.51e-05	1.14e-03	40
GO:00901309	Breast	Precancer	tissue migration	40/1080	365/18723	7.48e-05	1.47e-03	40
GO:00329709	Breast	Precancer	regulation of actin filament-based process	42/1080	397/18723	1.11e-04	2.01e-03	42
GO:00514959	Breast	Precancer	positive regulation of cytoskeleton organization	28/1080	226/18723	1.13e-04	2.04e-03	28
GO:00106329	Breast	Precancer	regulation of epithelial cell migration	33/1080	292/18723	1.74e-04	2.86e-03	33
GO:00016678	Breast	Precancer	ameboidal-type cell migration	47/1080	475/18723	2.19e-04	3.35e-03	47
GO:00434624	Breast	Precancer	regulation of ATPase activity	10/1080	46/18723	2.38e-04	3.57e-03	10
GO:00070159	Breast	Precancer	actin filament organization	44/1080	442/18723	3.02e-04	4.35e-03	44
GO:00329569	Breast	Precancer	regulation of actin cytoskeleton organization	36/1080	358/18723	8.56e-04	9.88e-03	36
GO:00351486	Breast	Precancer	tube formation	19/1080	148/18723	8.79e-04	1.01e-02	19
GO:00322739	Breast	Precancer	positive regulation of protein polymerization	18/1080	138/18723	9.85e-04	1.11e-02	18
GO:00313338	Breast	Precancer	negative regulation of protein-containing complex assembly	18/1080	141/18723	1.27e-03	1.35e-02	18

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0520523	Breast	IDC	Proteoglycans in cancer	42/867	205/8465	7.69e-06	9.99e-05	7.48e-05	42
hsa0510024	Breast	IDC	Bacterial invasion of epithelial cells	17/867	77/8465	1.69e-03	1.19e-02	8.93e-03	17
hsa0481014	Breast	IDC	Regulation of actin cytoskeleton	36/867	229/8465	5.79e-03	3.13e-02	2.34e-02	36
hsa045109	Breast	IDC	Focal adhesion	32/867	203/8465	8.60e-03	4.23e-02	3.17e-02	32
hsa0520533	Breast	IDC	Proteoglycans in cancer	42/867	205/8465	7.69e-06	9.99e-05	7.48e-05	42
hsa0510034	Breast	IDC	Bacterial invasion of epithelial cells	17/867	77/8465	1.69e-03	1.19e-02	8.93e-03	17
hsa0481015	Breast	IDC	Regulation of actin cytoskeleton	36/867	229/8465	5.79e-03	3.13e-02	2.34e-02	36
hsa0451013	Breast	IDC	Focal adhesion	32/867	203/8465	8.60e-03	4.23e-02	3.17e-02	32
hsa05205	Colorectum	AD	Proteoglycans in cancer	70/2092	205/8465	1.37e-03	8.46e-03	5.39e-03	70
hsa04810	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa04510	Colorectum	AD	Focal adhesion	67/2092	203/8465	4.40e-03	2.17e-02	1.38e-02	67
hsa052051	Colorectum	AD	Proteoglycans in cancer	70/2092	205/8465	1.37e-03	8.46e-03	5.39e-03	70
hsa048101	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa045101	Colorectum	AD	Focal adhesion	67/2092	203/8465	4.40e-03	2.17e-02	1.38e-02	67
hsa051004	Colorectum	MSS	Bacterial invasion of epithelial cells	36/1875	77/8465	1.41e-06	1.82e-05	1.11e-05	36
hsa051354	Colorectum	MSS	Yersinia infection	53/1875	137/8465	7.73e-06	8.93e-05	5.47e-05	53
hsa052054	Colorectum	MSS	Proteoglycans in cancer	65/1875	205/8465	8.66e-04	5.38e-03	3.29e-03	65
hsa048104	Colorectum	MSS	Regulation of actin cytoskeleton	68/1875	229/8465	4.27e-03	1.86e-02	1.14e-02	68
hsa05222	Colorectum	MSS	Small cell lung cancer	30/1875	92/8465	1.31e-02	4.30e-02	2.64e-02	30
hsa051005	Colorectum	MSS	Bacterial invasion of epithelial cells	36/1875	77/8465	1.41e-06	1.82e-05	1.11e-05	36

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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
FN1	ITGA4_ITGB1	FN1_ITGA4_ITGB1	FN1	Breast	ADJ
FN1	ITGA5_ITGB1	FN1_ITGA5_ITGB1	FN1	Breast	ADJ
FN1	CD44	FN1_CD44	FN1	Breast	ADJ
FN1	SDC4	FN1_SDC4	FN1	Breast	ADJ
FN1	ITGA4_ITGB1	FN1_ITGA4_ITGB1	FN1	Breast	DCIS
FN1	ITGA5_ITGB1	FN1_ITGA5_ITGB1	FN1	Breast	DCIS
FN1	ITGAV_ITGB1	FN1_ITGAV_ITGB1	FN1	Breast	DCIS
FN1	ITGA4_ITGB7	FN1_ITGA4_ITGB7	FN1	Breast	DCIS
FN1	CD44	FN1_CD44	FN1	Breast	DCIS
FN1	SDC1	FN1_SDC1	FN1	Breast	DCIS
FN1	SDC4	FN1_SDC4	FN1	Breast	DCIS
FN1	ITGA4_ITGB1	FN1_ITGA4_ITGB1	FN1	Breast	Healthy
FN1	ITGA5_ITGB1	FN1_ITGA5_ITGB1	FN1	Breast	Healthy
FN1	ITGAV_ITGB1	FN1_ITGAV_ITGB1	FN1	Breast	Healthy
FN1	ITGA4_ITGB7	FN1_ITGA4_ITGB7	FN1	Breast	Healthy
FN1	ITGAV_ITGB6	FN1_ITGAV_ITGB6	FN1	Breast	Healthy
FN1	ITGAV_ITGB8	FN1_ITGAV_ITGB8	FN1	Breast	Healthy
FN1	CD44	FN1_CD44	FN1	Breast	Healthy
FN1	SDC1	FN1_SDC1	FN1	Breast	Healthy
FN1	SDC4	FN1_SDC4	FN1	Breast	Healthy

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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

FN1

SNV

Missense_Mutation

c.7241N>A

p.Gly2414Glu

p.G2414E

P02751

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A2-A0SY-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

arimidex

FN1

SNV

Missense_Mutation

c.3291G>C

p.Glu1097Asp

p.E1097D

P02751

protein_coding

tolerated(0.31)

probably_damaging(0.992)

TCGA-A8-A085-01

Breast

breast invasive carcinoma

Male

<65

I/II

Hormone Therapy

tamoxiphen

FN1

SNV

Missense_Mutation

c.1094C>G

p.Thr365Ser

p.T365S

P02751

protein_coding

deleterious(0.02)

benign(0.066)

TCGA-A8-A09W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

FN1

SNV

Missense_Mutation

c.968N>C

p.Leu323Pro

p.L323P

P02751

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FN1

SNV

Missense_Mutation

rs750176227

c.274N>A

p.Glu92Lys

p.E92K

P02751

protein_coding

deleterious(0.01)

probably_damaging(0.992)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

FN1

SNV

Missense_Mutation

c.2488N>T

p.Arg830Cys

p.R830C

P02751

protein_coding

deleterious(0.01)

possibly_damaging(0.683)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FN1

SNV

Missense_Mutation

c.331A>G

p.Thr111Ala

p.T111A

P02751

protein_coding

deleterious(0.01)

probably_damaging(0.992)

TCGA-AN-A0XN-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

FN1

SNV

Missense_Mutation

c.4034N>A

p.Gly1345Asp

p.G1345D

P02751

protein_coding

tolerated(0.11)

probably_damaging(1)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

FN1

SNV

Missense_Mutation

rs149294265

c.7402N>A

p.Val2468Ile

p.V2468I

P02751

protein_coding

tolerated(0.1)

benign(0.023)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

FN1

SNV

Missense_Mutation

c.1717N>A

p.Gly573Arg

p.G573R

P02751

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-D8-A1JN-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozolum

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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
2335	FN1	DRUGGABLE GENOME		CHEMBL2109608	L19IL2
2335	FN1	DRUGGABLE GENOME		Ocriplasmin	OCRIPLASMIN
2335	FN1	DRUGGABLE GENOME		CHEMBL2095222	OCRIPLASMIN
2335	FN1	DRUGGABLE GENOME		AS1409
2335	FN1	DRUGGABLE GENOME		L19-TNF-alpha
2335	FN1	DRUGGABLE GENOME		CHEMBL2109589	L19TNFA
2335	FN1	DRUGGABLE GENOME		CHEMBL2109412	L19SIP 131I

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