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: DLG1

Gene summary for DLG1

Gene summary.

Gene information	Species	Human
	Gene symbol	DLG1
	Gene ID	1739
	Gene name	discs large MAGUK scaffold protein 1
	Gene Alias	DLGH1
	Cytomap	3q29
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q12959

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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
1739	DLG1	CA_HPV_2	Human	Cervix	CC	1.98e-02	2.22e-01	0.0391
1739	DLG1	CCI_1	Human	Cervix	CC	1.24e-27	2.41e+00	0.528
1739	DLG1	CCI_2	Human	Cervix	CC	3.31e-24	2.84e+00	0.5249
1739	DLG1	CCI_3	Human	Cervix	CC	4.67e-37	2.32e+00	0.516
1739	DLG1	Tumor	Human	Cervix	CC	9.70e-07	2.60e-01	0.1241
1739	DLG1	sample3	Human	Cervix	CC	2.68e-33	5.39e-01	0.1387
1739	DLG1	T3	Human	Cervix	CC	3.44e-24	4.93e-01	0.1389
1739	DLG1	HTA11_3410_2000001011	Human	Colorectum	AD	3.93e-43	-9.67e-01	0.0155
1739	DLG1	HTA11_2487_2000001011	Human	Colorectum	SER	2.29e-02	-4.74e-01	-0.1808
1739	DLG1	HTA11_2951_2000001011	Human	Colorectum	AD	9.19e-06	-7.17e-01	0.0216
1739	DLG1	HTA11_347_2000001011	Human	Colorectum	AD	5.38e-06	4.27e-01	-0.1954
1739	DLG1	HTA11_3361_2000001011	Human	Colorectum	AD	1.15e-12	-5.67e-01	-0.1207
1739	DLG1	HTA11_866_2000001011	Human	Colorectum	AD	2.97e-02	-2.85e-01	-0.1001
1739	DLG1	HTA11_9341_2000001011	Human	Colorectum	SER	5.76e-04	-8.21e-01	-0.00410000000000005
1739	DLG1	HTA11_866_3004761011	Human	Colorectum	AD	4.46e-16	-7.34e-01	0.096
1739	DLG1	HTA11_9408_2000001011	Human	Colorectum	AD	5.83e-03	-8.06e-01	0.0451
1739	DLG1	HTA11_8622_2000001021	Human	Colorectum	SER	2.94e-11	-8.81e-01	0.0528
1739	DLG1	HTA11_10623_2000001011	Human	Colorectum	AD	6.44e-06	-5.06e-01	-0.0177
1739	DLG1	HTA11_10711_2000001011	Human	Colorectum	AD	7.09e-07	-5.82e-01	0.0338
1739	DLG1	HTA11_7696_3000711011	Human	Colorectum	AD	2.77e-31	-6.80e-01	0.0674

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
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:199077820	Skin	AK	protein localization to cell periphery	66/1910	333/18723	9.18e-08	4.21e-06	66
GO:00448438	Skin	AK	cell cycle G1/S phase transition	52/1910	241/18723	1.32e-07	5.80e-06	52
GO:005067818	Skin	AK	regulation of epithelial cell proliferation	72/1910	381/18723	1.76e-07	7.28e-06	72
GO:004860819	Skin	AK	reproductive structure development	77/1910	424/18723	3.56e-07	1.36e-05	77
GO:000704319	Skin	AK	cell-cell junction assembly	36/1910	146/18723	3.88e-07	1.47e-05	36
GO:006145820	Skin	AK	reproductive system development	77/1910	427/18723	4.76e-07	1.74e-05	77
GO:004211019	Skin	AK	T cell activation	85/1910	487/18723	5.16e-07	1.85e-05	85
GO:002240725	Skin	AK	regulation of cell-cell adhesion	79/1910	448/18723	8.55e-07	2.81e-05	79
GO:003295628	Skin	AK	regulation of actin cytoskeleton organization	66/1910	358/18723	1.40e-06	4.26e-05	66
GO:004325428	Skin	AK	regulation of protein-containing complex assembly	75/1910	428/18723	2.05e-06	5.98e-05	75
GO:19019907	Skin	AK	regulation of mitotic cell cycle phase transition	57/1910	299/18723	2.47e-06	6.76e-05	57
GO:005140319	Skin	AK	stress-activated MAPK cascade	48/1910	239/18723	3.43e-06	8.82e-05	48
GO:003287218	Skin	AK	regulation of stress-activated MAPK cascade	41/1910	192/18723	3.57e-06	8.96e-05	41
GO:005165618	Skin	AK	establishment of organelle localization	69/1910	390/18723	3.69e-06	9.11e-05	69
GO:19019877	Skin	AK	regulation of cell cycle phase transition	69/1910	390/18723	3.69e-06	9.11e-05	69
GO:20000457	Skin	AK	regulation of G1/S transition of mitotic cell cycle	33/1910	142/18723	4.71e-06	1.12e-04	33
GO:007030218	Skin	AK	regulation of stress-activated protein kinase signaling cascade	41/1910	195/18723	5.36e-06	1.24e-04	41
GO:011005328	Skin	AK	regulation of actin filament organization	53/1910	278/18723	5.48e-06	1.26e-04	53
GO:003109819	Skin	AK	stress-activated protein kinase signaling cascade	48/1910	247/18723	8.76e-06	1.89e-04	48
GO:005086317	Skin	AK	regulation of T cell activation	59/1910	329/18723	1.20e-05	2.46e-04	59

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0516620	Cervix	CC	Human T-cell leukemia virus 1 infection	61/1267	222/8465	8.13e-07	7.98e-06	4.72e-06	61
hsa0453020	Cervix	CC	Tight junction	49/1267	169/8465	1.87e-06	1.78e-05	1.05e-05	49
hsa051657	Cervix	CC	Human papillomavirus infection	74/1267	331/8465	1.70e-04	1.02e-03	6.03e-04	74
hsa043908	Cervix	CC	Hippo signaling pathway	40/1267	157/8465	3.64e-04	1.82e-03	1.07e-03	40
hsa046604	Cervix	CC	T cell receptor signaling pathway	25/1267	104/8465	9.52e-03	2.94e-02	1.74e-02	25
hsa05166110	Cervix	CC	Human T-cell leukemia virus 1 infection	61/1267	222/8465	8.13e-07	7.98e-06	4.72e-06	61
hsa04530110	Cervix	CC	Tight junction	49/1267	169/8465	1.87e-06	1.78e-05	1.05e-05	49
hsa0516512	Cervix	CC	Human papillomavirus infection	74/1267	331/8465	1.70e-04	1.02e-03	6.03e-04	74
hsa0439013	Cervix	CC	Hippo signaling pathway	40/1267	157/8465	3.64e-04	1.82e-03	1.07e-03	40
hsa0466011	Cervix	CC	T cell receptor signaling pathway	25/1267	104/8465	9.52e-03	2.94e-02	1.74e-02	25
hsa04530	Colorectum	AD	Tight junction	76/2092	169/8465	5.49e-09	9.69e-08	6.18e-08	76
hsa05166	Colorectum	AD	Human T-cell leukemia virus 1 infection	72/2092	222/8465	5.24e-03	2.44e-02	1.55e-02	72
hsa045301	Colorectum	AD	Tight junction	76/2092	169/8465	5.49e-09	9.69e-08	6.18e-08	76
hsa051661	Colorectum	AD	Human T-cell leukemia virus 1 infection	72/2092	222/8465	5.24e-03	2.44e-02	1.55e-02	72
hsa045302	Colorectum	SER	Tight junction	59/1580	169/8465	3.24e-07	5.98e-06	4.34e-06	59
hsa045303	Colorectum	SER	Tight junction	59/1580	169/8465	3.24e-07	5.98e-06	4.34e-06	59
hsa045304	Colorectum	MSS	Tight junction	66/1875	169/8465	4.10e-07	6.25e-06	3.83e-06	66
hsa051662	Colorectum	MSS	Human T-cell leukemia virus 1 infection	68/1875	222/8465	1.84e-03	9.61e-03	5.89e-03	68
hsa04390	Colorectum	MSS	Hippo signaling pathway	48/1875	157/8465	8.32e-03	3.10e-02	1.90e-02	48
hsa045305	Colorectum	MSS	Tight junction	66/1875	169/8465	4.10e-07	6.25e-06	3.83e-06	66

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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

DLG1

SNV

Missense_Mutation

novel

c.301N>A

p.Leu101Ile

p.L101I

Q12959

protein_coding

tolerated_low_confidence(0.17)

possibly_damaging(0.689)

TCGA-A2-A4S1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DLG1

SNV

Missense_Mutation

c.731N>C

p.Asn244Thr

p.N244T

Q12959

protein_coding

deleterious(0.03)

probably_damaging(0.999)

TCGA-A8-A083-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DLG1

SNV

Missense_Mutation

novel

c.1434N>G

p.Phe478Leu

p.F478L

Q12959

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

DLG1

SNV

Missense_Mutation

c.16N>G

p.Gln6Glu

p.Q6E

Q12959

protein_coding

tolerated(0.38)

benign(0)

TCGA-AN-A0FW-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

DLG1

SNV

Missense_Mutation

c.1186N>T

p.Asp396Tyr

p.D396Y

Q12959

protein_coding

deleterious(0)

probably_damaging(0.987)

TCGA-BH-A0AZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

DLG1

SNV

Missense_Mutation

novel

c.2516N>C

p.Arg839Thr

p.R839T

Q12959

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BH-A209-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DLG1

SNV

Missense_Mutation

c.2251G>T

p.Asp751Tyr

p.D751Y

Q12959

protein_coding

deleterious(0)

probably_damaging(0.978)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DLG1

SNV

Missense_Mutation

c.1692G>A

p.Met564Ile

p.M564I

Q12959

protein_coding

tolerated(0.07)

benign(0.406)

TCGA-D8-A1JJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

DLG1

SNV

Missense_Mutation

novel

c.2013N>A

p.Phe671Leu

p.F671L

Q12959

protein_coding

tolerated(0.92)

benign(0)

TCGA-E2-A1LG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

DLG1

SNV

Missense_Mutation

novel

c.2432N>G

p.Tyr811Cys

p.Y811C

Q12959

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-LL-A740-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

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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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