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: GHR

Gene summary for GHR

Gene summary.

Gene information	Species	Human
	Gene symbol	GHR
	Gene ID	2690
	Gene name	growth hormone receptor
	Gene Alias	GHBP
	Cytomap	5p13.1-p12
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	P10912

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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
2690	GHR	HTA11_3410_2000001011	Human	Colorectum	AD	5.45e-13	-5.10e-01	0.0155
2690	GHR	HTA11_2487_2000001011	Human	Colorectum	SER	1.75e-08	-5.28e-01	-0.1808
2690	GHR	HTA11_1938_2000001011	Human	Colorectum	AD	7.11e-05	-5.11e-01	-0.0811
2690	GHR	HTA11_78_2000001011	Human	Colorectum	AD	1.53e-02	-4.08e-01	-0.1088
2690	GHR	HTA11_696_2000001011	Human	Colorectum	AD	2.63e-04	-3.25e-01	-0.1464
2690	GHR	HTA11_1391_2000001011	Human	Colorectum	AD	4.10e-05	-4.27e-01	-0.059
2690	GHR	HTA11_866_3004761011	Human	Colorectum	AD	4.30e-07	-4.49e-01	0.096
2690	GHR	HTA11_8622_2000001021	Human	Colorectum	SER	3.27e-03	-5.38e-01	0.0528
2690	GHR	HTA11_10711_2000001011	Human	Colorectum	AD	9.07e-07	-5.16e-01	0.0338
2690	GHR	HTA11_7696_3000711011	Human	Colorectum	AD	2.25e-12	-4.58e-01	0.0674
2690	GHR	HTA11_99999970781_79442	Human	Colorectum	MSS	3.62e-02	-2.64e-01	0.294
2690	GHR	HTA11_99999971662_82457	Human	Colorectum	MSS	7.80e-03	-3.42e-01	0.3859
2690	GHR	HTA11_99999973899_84307	Human	Colorectum	MSS	6.15e-04	-5.21e-01	0.2585
2690	GHR	HTA11_99999974143_84620	Human	Colorectum	MSS	2.38e-12	-4.76e-01	0.3005
2690	GHR	F007	Human	Colorectum	FAP	2.03e-08	-5.09e-01	0.1176
2690	GHR	A002-C-010	Human	Colorectum	FAP	2.97e-16	-4.58e-01	0.242
2690	GHR	A001-C-207	Human	Colorectum	FAP	3.44e-08	-4.58e-01	0.1278
2690	GHR	A015-C-203	Human	Colorectum	FAP	6.59e-13	-3.84e-01	-0.1294
2690	GHR	A015-C-204	Human	Colorectum	FAP	1.68e-11	-5.04e-01	-0.0228
2690	GHR	A002-C-201	Human	Colorectum	FAP	1.72e-18	-5.30e-01	0.0324

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease

∗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:0032868	Colorectum	AD	response to insulin	91/3918	264/18723	2.02e-07	8.48e-06	91
GO:1901653	Colorectum	AD	cellular response to peptide	114/3918	359/18723	8.32e-07	2.88e-05	114
GO:0032869	Colorectum	AD	cellular response to insulin stimulus	72/3918	203/18723	1.10e-06	3.68e-05	72
GO:0070997	Colorectum	AD	neuron death	114/3918	361/18723	1.13e-06	3.72e-05	114
GO:0071375	Colorectum	AD	cellular response to peptide hormone stimulus	95/3918	290/18723	1.50e-06	4.66e-05	95
GO:0043434	Colorectum	AD	response to peptide hormone	126/3918	414/18723	2.70e-06	7.86e-05	126
GO:0031667	Colorectum	AD	response to nutrient levels	138/3918	474/18723	1.22e-05	2.68e-04	138
GO:1901214	Colorectum	AD	regulation of neuron death	99/3918	319/18723	1.26e-05	2.76e-04	99
GO:0048545	Colorectum	AD	response to steroid hormone	104/3918	339/18723	1.33e-05	2.90e-04	104
GO:0009755	Colorectum	AD	hormone-mediated signaling pathway	64/3918	190/18723	2.78e-05	5.24e-04	64
GO:0006790	Colorectum	AD	sulfur compound metabolic process	101/3918	339/18723	6.46e-05	1.07e-03	101
GO:1901215	Colorectum	AD	negative regulation of neuron death	67/3918	208/18723	8.81e-05	1.35e-03	67
GO:0033674	Colorectum	AD	positive regulation of kinase activity	131/3918	467/18723	1.28e-04	1.85e-03	131
GO:0045927	Colorectum	AD	positive regulation of growth	77/3918	259/18723	4.82e-04	5.27e-03	77
GO:0045860	Colorectum	AD	positive regulation of protein kinase activity	107/3918	386/18723	8.01e-04	7.92e-03	107
GO:0048638	Colorectum	AD	regulation of developmental growth	92/3918	330/18723	1.48e-03	1.25e-02	92
GO:0071900	Colorectum	AD	regulation of protein serine/threonine kinase activity	98/3918	359/18723	2.18e-03	1.73e-02	98
GO:0048639	Colorectum	AD	positive regulation of developmental growth	52/3918	174/18723	3.24e-03	2.38e-02	52
GO:0071902	Colorectum	AD	positive regulation of protein serine/threonine kinase activity	58/3918	200/18723	4.09e-03	2.84e-02	58
GO:00316671	Colorectum	SER	response to nutrient levels	106/2897	474/18723	3.94e-05	1.00e-03	106

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04935	Colorectum	MSS	Growth hormone synthesis, secretion and action	42/1875	120/8465	8.17e-04	5.16e-03	3.16e-03	42
hsa049351	Colorectum	MSS	Growth hormone synthesis, secretion and action	42/1875	120/8465	8.17e-04	5.16e-03	3.16e-03	42
hsa049352	Colorectum	FAP	Growth hormone synthesis, secretion and action	34/1404	120/8465	8.12e-04	5.14e-03	3.13e-03	34
hsa04151	Colorectum	FAP	PI3K-Akt signaling pathway	75/1404	354/8465	1.23e-02	4.19e-02	2.55e-02	75
hsa049353	Colorectum	FAP	Growth hormone synthesis, secretion and action	34/1404	120/8465	8.12e-04	5.14e-03	3.13e-03	34
hsa041511	Colorectum	FAP	PI3K-Akt signaling pathway	75/1404	354/8465	1.23e-02	4.19e-02	2.55e-02	75
hsa049354	Colorectum	CRC	Growth hormone synthesis, secretion and action	27/1091	120/8465	2.37e-03	1.69e-02	1.14e-02	27
hsa041512	Colorectum	CRC	PI3K-Akt signaling pathway	64/1091	354/8465	2.70e-03	1.77e-02	1.20e-02	64
hsa049355	Colorectum	CRC	Growth hormone synthesis, secretion and action	27/1091	120/8465	2.37e-03	1.69e-02	1.14e-02	27
hsa041513	Colorectum	CRC	PI3K-Akt signaling pathway	64/1091	354/8465	2.70e-03	1.77e-02	1.20e-02	64

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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

GHR

SNV

Missense_Mutation

c.1288N>A

p.Leu430Ile

p.L430I

protein_coding

deleterious(0.03)

possibly_damaging(0.506)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GHR

SNV

Missense_Mutation

novel

c.1859N>T

p.Ala620Val

p.A620V

protein_coding

tolerated(0.24)

probably_damaging(0.998)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GHR

SNV

Missense_Mutation

c.402N>G

p.Ile134Met

p.I134M

protein_coding

tolerated(0.38)

probably_damaging(0.985)

TCGA-AO-A03V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

GHR

insertion

Nonsense_Mutation

novel

c.151_152insCCTTAGCCCCGAGGTAGTGTCTAGGGGTGGGGTGCCTGCAACCCC

p.Lys51delinsThrLeuAlaProArgTerCysLeuGlyValGlyCysLeuGlnProGln

p.K51delinsTLAPR*CLGVGCLQPQ

protein_coding

TCGA-AN-A04C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

GHR

insertion

Frame_Shift_Ins

novel

c.1715_1716insCAAAATGAGATCTATG

p.Tyr573LysfsTer29

p.Y573Kfs*29

protein_coding

TCGA-AO-A03R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

GHR

insertion

Frame_Shift_Ins

novel

c.804_805insT

p.Asp269Ter

p.D269*

protein_coding

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

GHR

deletion

Frame_Shift_Del

novel

c.302delN

p.Trp101Ter

p.W101*

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

GHR

SNV

Missense_Mutation

c.113G>C

p.Arg38Thr

p.R38T

protein_coding

tolerated_low_confidence(0.26)

benign(0.075)

TCGA-EA-A3HQ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

GHR

SNV

Missense_Mutation

c.1759N>A

p.Gly587Arg

p.G587R

protein_coding

tolerated(0.36)

possibly_damaging(0.453)

TCGA-EK-A2GZ-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

GHR

SNV

Missense_Mutation

rs775194712

c.1853C>T

p.Ala618Val

p.A618V

protein_coding

deleterious(0.02)

probably_damaging(0.974)

TCGA-EX-A3L1-01

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
2690	GHR	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE		Syntropin
2690	GHR	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE		EP-51216
2690	GHR	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE		ACCCRETROPIN
2690	GHR	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE		BVT-A
2690	GHR	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE		Pegvisomant	PEGVISOMANT
2690	GHR	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE		ACP-001	ACP-001
2690	GHR	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE		AOD9604
2690	GHR	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE	agonist	178101641
2690	GHR	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE	antagonist	CHEMBL1201515	PEGVISOMANT
2690	GHR	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE	agonist	CHEMBL1201620	SOMATREM

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