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: GRB7

Gene summary for GRB7

Gene summary.

Gene information	Species	Human
	Gene symbol	GRB7
	Gene ID	2886
	Gene name	growth factor receptor bound protein 7
	Gene Alias	GRB7
	Cytomap	17q12
	Gene Type	protein-coding
	GO ID	GO:0006412
	UniProtAcc	A0A0S2Z4F6

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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
2886	GRB7	GSM4909287	Human	Breast	IDC	4.32e-05	-1.98e-01	0.2057
2886	GRB7	GSM4909290	Human	Breast	IDC	3.50e-32	9.03e-01	0.2096
2886	GRB7	GSM4909291	Human	Breast	IDC	1.10e-51	1.21e+00	0.1753
2886	GRB7	GSM4909292	Human	Breast	IDC	6.56e-09	8.94e-01	0.1236
2886	GRB7	GSM4909293	Human	Breast	IDC	3.22e-32	5.94e-01	0.1581
2886	GRB7	GSM4909294	Human	Breast	IDC	3.98e-19	4.95e-01	0.2022
2886	GRB7	GSM4909302	Human	Breast	IDC	2.98e-02	-1.64e-01	0.1545
2886	GRB7	GSM4909311	Human	Breast	IDC	7.75e-06	-2.29e-01	0.1534
2886	GRB7	GSM4909312	Human	Breast	IDC	6.24e-05	-1.70e-01	0.1552
2886	GRB7	GSM4909319	Human	Breast	IDC	7.22e-14	-9.39e-02	0.1563
2886	GRB7	GSM4909320	Human	Breast	IDC	2.80e-02	-1.38e-01	0.1575
2886	GRB7	GSM4909321	Human	Breast	IDC	1.48e-04	-5.21e-02	0.1559
2886	GRB7	brca3	Human	Breast	Precancer	6.30e-09	2.91e-01	-0.0263
2886	GRB7	M1	Human	Breast	IDC	1.32e-03	-2.19e-01	0.1577
2886	GRB7	M2	Human	Breast	IDC	3.93e-05	5.50e-01	0.21
2886	GRB7	NCCBC14	Human	Breast	DCIS	7.13e-11	5.25e-01	0.2021
2886	GRB7	NCCBC5	Human	Breast	DCIS	1.39e-09	3.09e-01	0.2046
2886	GRB7	P1	Human	Breast	IDC	9.37e-08	-2.26e-01	0.1527
2886	GRB7	P2	Human	Breast	IDC	1.59e-06	5.46e-01	0.21
2886	GRB7	DCIS2	Human	Breast	DCIS	5.14e-15	-4.24e-02	0.0085

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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
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:00064179	Breast	Precancer	regulation of translation	67/1080	468/18723	4.71e-12	7.64e-10	67
GO:00340635	Breast	Precancer	stress granule assembly	6/1080	26/18723	3.09e-03	2.62e-02	6
GO:000641714	Breast	IDC	regulation of translation	74/1434	468/18723	1.67e-09	1.53e-07	74
GO:000641724	Breast	DCIS	regulation of translation	72/1390	468/18723	2.46e-09	2.17e-07	72
GO:0038127	Colorectum	AD	ERBB signaling pathway	55/3918	121/18723	1.19e-09	8.85e-08	55
GO:0007173	Colorectum	AD	epidermal growth factor receptor signaling pathway	50/3918	108/18723	3.08e-09	2.07e-07	50
GO:0006417	Colorectum	AD	regulation of translation	141/3918	468/18723	1.32e-06	4.22e-05	141
GO:00064172	Colorectum	MSS	regulation of translation	134/3467	468/18723	4.43e-08	2.38e-06	134
GO:00071732	Colorectum	MSS	epidermal growth factor receptor signaling pathway	43/3467	108/18723	1.92e-07	8.31e-06	43
GO:00381272	Colorectum	MSS	ERBB signaling pathway	46/3467	121/18723	3.63e-07	1.45e-05	46
GO:0017148	Colorectum	MSS	negative regulation of translation	64/3467	245/18723	1.94e-03	1.67e-02	64
GO:0034249	Colorectum	MSS	negative regulation of cellular amide metabolic process	70/3467	273/18723	2.07e-03	1.76e-02	70
GO:0006417111	Esophagus	ESCC	regulation of translation	304/8552	468/18723	1.53e-17	1.33e-15	304
GO:003812718	Esophagus	ESCC	ERBB signaling pathway	82/8552	121/18723	7.23e-07	9.40e-06	82
GO:000717318	Esophagus	ESCC	epidermal growth factor receptor signaling pathway	73/8552	108/18723	3.36e-06	3.73e-05	73
GO:003406315	Esophagus	ESCC	stress granule assembly	23/8552	26/18723	6.82e-06	6.90e-05	23
GO:003424914	Esophagus	ESCC	negative regulation of cellular amide metabolic process	144/8552	273/18723	1.08e-02	3.67e-02	144
GO:000641712	Liver	Cirrhotic	regulation of translation	194/4634	468/18723	7.28e-16	8.79e-14	194
GO:003406311	Liver	Cirrhotic	stress granule assembly	18/4634	26/18723	2.21e-06	4.10e-05	18
GO:003424911	Liver	Cirrhotic	negative regulation of cellular amide metabolic process	100/4634	273/18723	7.34e-06	1.13e-04	100

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

GRB7

SNV

Missense_Mutation

novel

c.118N>T

p.Leu40Phe

p.L40F

Q14451

protein_coding

deleterious(0.03)

benign(0.112)

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

GRB7

SNV

Missense_Mutation

c.549N>A

p.Asp183Glu

p.D183E

Q14451

protein_coding

deleterious(0.02)

probably_damaging(0.993)

TCGA-B6-A400-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

GRB7

SNV

Missense_Mutation

rs368887935

c.233N>A

p.Arg78Gln

p.R78Q

Q14451

protein_coding

tolerated(1)

possibly_damaging(0.801)

TCGA-BH-A0BR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

GRB7

SNV

Missense_Mutation

c.461N>A

p.Leu154Gln

p.L154Q

Q14451

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A18V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

GRB7

SNV

Missense_Mutation

c.454N>C

p.Glu152Gln

p.E152Q

Q14451

protein_coding

tolerated(1)

possibly_damaging(0.812)

TCGA-D8-A1J9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

GRB7

SNV

Missense_Mutation

c.189G>C

p.Lys63Asn

p.K63N

Q14451

protein_coding

deleterious(0.04)

benign(0.012)

TCGA-EW-A1J5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

GRB7

insertion

In_Frame_Ins

novel

c.1602_1603insAGCCATCCACCGCACCCAACTCTGGTTCCACGGGCG

p.Phe534_His535insSerHisProProHisProThrLeuValProArgAla

p.F534_H535insSHPPHPTLVPRA

Q14451

protein_coding

TCGA-A8-A07O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

GRB7

insertion

In_Frame_Ins

novel

c.120_121insGTGCTAAAGAAAGAGCACTGGAGCCGGGCG

p.Leu40_Cys41insValLeuLysLysGluHisTrpSerArgAla

p.L40_C41insVLKKEHWSRA

Q14451

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

GRB7

insertion

In_Frame_Ins

novel

c.62_63insTCTGGCAACTGGGTCTGGCAACAAAGTGCTGGA

p.Ser21_Asp22insLeuAlaThrGlySerGlyAsnLysValLeuGlu

p.S21_D22insLATGSGNKVLE

Q14451

protein_coding

TCGA-BH-A0B4-01

Breast

breast invasive carcinoma

Male

>=65

III/IV

Hormone Therapy

tamoxiphen

GRB7

insertion

Frame_Shift_Ins

novel

c.942_943insTTGAGGCAGCCCCCGCCCCAGGA

p.Tyr316ArgfsTer80

p.Y316Rfs*80

Q14451

protein_coding

TCGA-C8-A12Z-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

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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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