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: AGT

Gene summary for AGT

Gene summary.

Gene information	Species	Human
	Gene symbol	AGT
	Gene ID	183
	Gene name	angiotensinogen
	Gene Alias	ANHU
	Cytomap	1q42.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	B0ZBE2

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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
183	AGT	NAFLD1	Human	Liver	NAFLD	4.58e-03	-3.05e-01	-0.04
183	AGT	S42	Human	Liver	HCC	2.40e-02	-4.14e-01	-0.0103
183	AGT	S43	Human	Liver	Cirrhotic	7.79e-28	-1.08e-01	-0.0187
183	AGT	HCC1_Meng	Human	Liver	HCC	2.73e-41	6.72e-01	0.0246
183	AGT	HCC2_Meng	Human	Liver	HCC	8.23e-41	-9.86e-01	0.0107
183	AGT	cirrhotic1	Human	Liver	Cirrhotic	5.97e-29	6.14e-01	0.0202
183	AGT	cirrhotic2	Human	Liver	Cirrhotic	2.37e-20	4.13e-01	0.0201
183	AGT	HCC1	Human	Liver	HCC	1.03e-25	5.85e+00	0.5336
183	AGT	HCC2	Human	Liver	HCC	2.33e-29	5.83e+00	0.5341
183	AGT	HCC5	Human	Liver	HCC	3.96e-03	1.91e+00	0.4932
183	AGT	Pt13.a	Human	Liver	HCC	1.99e-03	2.09e-01	0.021
183	AGT	Pt13.b	Human	Liver	HCC	2.28e-26	1.73e-01	0.0251
183	AGT	Pt14.a	Human	Liver	HCC	1.54e-04	2.14e-01	0.0169
183	AGT	Pt14.b	Human	Liver	HCC	9.40e-11	2.22e-01	0.018
183	AGT	S014	Human	Liver	HCC	8.01e-36	4.30e+00	0.2254
183	AGT	S015	Human	Liver	HCC	3.00e-44	4.72e+00	0.2375
183	AGT	S016	Human	Liver	HCC	9.89e-43	4.70e+00	0.2243
183	AGT	S027	Human	Liver	HCC	1.95e-20	2.60e+00	0.2446
183	AGT	S028	Human	Liver	HCC	3.71e-33	2.88e+00	0.2503
183	AGT	S029	Human	Liver	HCC	9.24e-41	3.24e+00	0.2581

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
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:00109517	Liver	NAFLD	negative regulation of endopeptidase activity	42/1882	252/18723	7.29e-04	9.29e-03	42
GO:00336736	Liver	NAFLD	negative regulation of kinase activity	40/1882	237/18723	7.49e-04	9.50e-03	40
GO:00075687	Liver	NAFLD	aging	53/1882	339/18723	7.78e-04	9.77e-03	53
GO:0032368	Liver	NAFLD	regulation of lipid transport	28/1882	149/18723	8.39e-04	1.03e-02	28
GO:00104667	Liver	NAFLD	negative regulation of peptidase activity	43/1882	262/18723	8.76e-04	1.07e-02	43
GO:00462097	Liver	NAFLD	nitric oxide metabolic process	18/1882	81/18723	9.60e-04	1.14e-02	18
GO:00454287	Liver	NAFLD	regulation of nitric oxide biosynthetic process	15/1882	62/18723	9.92e-04	1.18e-02	15
GO:20010577	Liver	NAFLD	reactive nitrogen species metabolic process	18/1882	82/18723	1.12e-03	1.29e-02	18
GO:0034433	Liver	NAFLD	steroid esterification	7/1882	18/18723	1.20e-03	1.37e-02	7
GO:0034434	Liver	NAFLD	sterol esterification	7/1882	18/18723	1.20e-03	1.37e-02	7
GO:0034435	Liver	NAFLD	cholesterol esterification	7/1882	18/18723	1.20e-03	1.37e-02	7
GO:1990776	Liver	NAFLD	response to angiotensin	9/1882	28/18723	1.20e-03	1.38e-02	9
GO:00801647	Liver	NAFLD	regulation of nitric oxide metabolic process	15/1882	64/18723	1.40e-03	1.57e-02	15
GO:1900076	Liver	NAFLD	regulation of cellular response to insulin stimulus	15/1882	64/18723	1.40e-03	1.57e-02	15
GO:00725947	Liver	NAFLD	establishment of protein localization to organelle	62/1882	422/18723	1.48e-03	1.64e-02	62
GO:00454296	Liver	NAFLD	positive regulation of nitric oxide biosynthetic process	11/1882	40/18723	1.51e-03	1.64e-02	11
GO:00019337	Liver	NAFLD	negative regulation of protein phosphorylation	52/1882	342/18723	1.63e-03	1.74e-02	52
GO:0045834	Liver	NAFLD	positive regulation of lipid metabolic process	27/1882	149/18723	1.80e-03	1.85e-02	27
GO:00033001	Liver	NAFLD	cardiac muscle hypertrophy	20/1882	99/18723	1.80e-03	1.85e-02	20
GO:19044076	Liver	NAFLD	positive regulation of nitric oxide metabolic process	11/1882	41/18723	1.88e-03	1.92e-02	11

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0541514	Liver	Cirrhotic	Diabetic cardiomyopathy	108/2530	203/8465	1.99e-12	4.41e-11	2.72e-11	108
hsa0541515	Liver	Cirrhotic	Diabetic cardiomyopathy	108/2530	203/8465	1.99e-12	4.41e-11	2.72e-11	108

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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
AGT	AGTR1	AGT_AGTR1B	AGT	Esophagus	ESCC
AGT	AGTR1	AGT_AGTR1B	AGT	HNSCC	ADJ
AGT	AGTR1	AGT_AGTR1B	AGT	Liver	Healthy
AGT	AGTR1	AGT_AGTR1B	AGT	Liver	Precancer
AGT	AGTR1	AGT_AGTR1B	AGT	THCA	Precancer

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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

AGT

SNV

Missense_Mutation

c.257N>T

p.Asp86Val

p.D86V

P01019

protein_coding

tolerated(0.09)

benign(0.007)

TCGA-A8-A08F-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

AGT

SNV

Missense_Mutation

c.559N>T

p.Val187Leu

p.V187L

P01019

protein_coding

deleterious(0.01)

benign(0.088)

TCGA-C8-A134-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

AGT

SNV

Missense_Mutation

c.1052N>G

p.Ser351Cys

p.S351C

P01019

protein_coding

deleterious(0)

possibly_damaging(0.729)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

AGT

SNV

Missense_Mutation

novel

c.740C>A

p.Ala247Asp

p.A247D

P01019

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-D8-A27F-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin+cyclophosphamide

AGT

SNV

Missense_Mutation

novel

c.815T>A

p.Val272Glu

p.V272E

P01019

protein_coding

deleterious(0)

benign(0)

TCGA-OL-A6VQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

AGT

insertion

Frame_Shift_Ins

novel

c.718_719insT

p.Asp240ValfsTer10

p.D240Vfs*10

P01019

protein_coding

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

AGT

insertion

Frame_Shift_Ins

novel

c.716_717insAGGATTTGGAGCTGCAGGGAAACGTGCTCCACAA

p.Asp240GlyfsTer21

p.D240Gfs*21

P01019

protein_coding

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

AGT

insertion

In_Frame_Ins

novel

c.949_950insAGGAGAGGAAGAATGCTTTTTCTACAC

p.Gly317delinsGluGluArgLysAsnAlaPheSerThrArg

p.G317delinsEERKNAFSTR

P01019

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

AGT

insertion

Frame_Shift_Ins

novel

c.366_367insTTGAAGGTTACGCAAG

p.Glu123LeufsTer39

p.E123Lfs*39

P01019

protein_coding

TCGA-B6-A0RG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

AGT

SNV

Missense_Mutation

rs760531325

c.142N>A

p.Glu48Lys

p.E48K

P01019

protein_coding

tolerated(1)

benign(0)

TCGA-IR-A3LH-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
183	AGT	ENZYME, DRUGGABLE GENOME, PROTEASE INHIBITOR, G PROTEIN COUPLED RECEPTOR, HORMONE ACTIVITY, GROWTH FACTOR		QUINAPRIL	QUINAPRIL	12693379,11849656
183	AGT	ENZYME, DRUGGABLE GENOME, PROTEASE INHIBITOR, G PROTEIN COUPLED RECEPTOR, HORMONE ACTIVITY, GROWTH FACTOR		chlorthalidone	CHLORTHALIDONE
183	AGT	ENZYME, DRUGGABLE GENOME, PROTEASE INHIBITOR, G PROTEIN COUPLED RECEPTOR, HORMONE ACTIVITY, GROWTH FACTOR		CYCLOSPORIN A		10642325
183	AGT	ENZYME, DRUGGABLE GENOME, PROTEASE INHIBITOR, G PROTEIN COUPLED RECEPTOR, HORMONE ACTIVITY, GROWTH FACTOR		ADENOVIRUS VECTOR		16014023
183	AGT	ENZYME, DRUGGABLE GENOME, PROTEASE INHIBITOR, G PROTEIN COUPLED RECEPTOR, HORMONE ACTIVITY, GROWTH FACTOR		Antiinflammatory agents, non-steroids		20538124
183	AGT	ENZYME, DRUGGABLE GENOME, PROTEASE INHIBITOR, G PROTEIN COUPLED RECEPTOR, HORMONE ACTIVITY, GROWTH FACTOR		CORTISOL	HYDROCORTISONE	15576665
183	AGT	ENZYME, DRUGGABLE GENOME, PROTEASE INHIBITOR, G PROTEIN COUPLED RECEPTOR, HORMONE ACTIVITY, GROWTH FACTOR		Ace Inhibitors, Plain		14643574
183	AGT	ENZYME, DRUGGABLE GENOME, PROTEASE INHIBITOR, G PROTEIN COUPLED RECEPTOR, HORMONE ACTIVITY, GROWTH FACTOR		atenolol	ATENOLOL	11593098,14700505
183	AGT	ENZYME, DRUGGABLE GENOME, PROTEASE INHIBITOR, G PROTEIN COUPLED RECEPTOR, HORMONE ACTIVITY, GROWTH FACTOR		irbesartan	IRBESARTAN	11593098,15614026,14700505
183	AGT	ENZYME, DRUGGABLE GENOME, PROTEASE INHIBITOR, G PROTEIN COUPLED RECEPTOR, HORMONE ACTIVITY, GROWTH FACTOR		ANTI-ANGIOGENIC AGENTS		15578913

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