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: AQP5

Gene summary for AQP5

Gene summary.

Gene information	Species	Human
	Gene symbol	AQP5
	Gene ID	362
	Gene name	aquaporin 5
	Gene Alias	AQP-5
	Cytomap	12q13.12
	Gene Type	protein-coding
	GO ID	GO:0001654
	UniProtAcc	P55064

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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
362	AQP5	GSM4909286	Human	Breast	IDC	5.46e-23	5.25e-01	0.1081
362	AQP5	GSM4909290	Human	Breast	IDC	1.71e-33	9.46e-01	0.2096
362	AQP5	GSM4909291	Human	Breast	IDC	3.22e-03	-2.12e-01	0.1753
362	AQP5	GSM4909293	Human	Breast	IDC	1.06e-03	-1.93e-01	0.1581
362	AQP5	GSM4909297	Human	Breast	IDC	1.84e-03	-2.03e-01	0.1517
362	AQP5	GSM4909298	Human	Breast	IDC	3.19e-05	-2.09e-01	0.1551
362	AQP5	GSM4909301	Human	Breast	IDC	8.30e-08	-2.12e-01	0.1577
362	AQP5	GSM4909302	Human	Breast	IDC	5.94e-07	-2.12e-01	0.1545
362	AQP5	GSM4909304	Human	Breast	IDC	3.84e-07	-2.06e-01	0.1636
362	AQP5	GSM4909306	Human	Breast	IDC	1.51e-02	-1.96e-01	0.1564
362	AQP5	GSM4909307	Human	Breast	IDC	1.21e-05	-2.09e-01	0.1569
362	AQP5	GSM4909308	Human	Breast	IDC	5.80e-06	-2.12e-01	0.158
362	AQP5	GSM4909309	Human	Breast	IDC	5.43e-06	-2.12e-01	0.0483
362	AQP5	GSM4909311	Human	Breast	IDC	8.30e-08	-2.12e-01	0.1534
362	AQP5	GSM4909312	Human	Breast	IDC	1.31e-04	-1.98e-01	0.1552
362	AQP5	GSM4909315	Human	Breast	IDC	1.77e-06	-2.12e-01	0.21
362	AQP5	GSM4909319	Human	Breast	IDC	1.77e-06	-2.12e-01	0.1563
362	AQP5	GSM4909321	Human	Breast	IDC	3.85e-08	-2.12e-01	0.1559
362	AQP5	brca10	Human	Breast	Precancer	1.05e-05	-2.12e-01	-0.0029
362	AQP5	M1	Human	Breast	IDC	5.20e-03	-2.12e-01	0.1577

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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
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
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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma

∗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:0001654	Cervix	CC	eye development	62/2311	371/18723	7.83e-03	4.13e-02	62
GO:0048880	Cervix	CC	sensory system development	63/2311	381/18723	9.29e-03	4.66e-02	63
GO:005087814	Cervix	HSIL_HPV	regulation of body fluid levels	37/737	379/18723	3.81e-07	2.06e-05	37
GO:006219715	Cervix	HSIL_HPV	cellular response to chemical stress	29/737	337/18723	7.17e-05	1.65e-03	29
GO:00621971	Colorectum	SER	cellular response to chemical stress	87/2897	337/18723	5.33e-07	2.59e-05	87
GO:0022600	Colorectum	SER	digestive system process	29/2897	104/18723	8.57e-04	1.05e-02	29
GO:00508781	Colorectum	SER	regulation of body fluid levels	81/2897	379/18723	1.28e-03	1.43e-02	81
GO:00075891	Colorectum	SER	body fluid secretion	26/2897	93/18723	1.49e-03	1.60e-02	26
GO:0032941	Colorectum	SER	secretion by tissue	13/2897	38/18723	3.40e-03	2.90e-02	13
GO:0006970	Colorectum	SER	response to osmotic stress	23/2897	84/18723	3.61e-03	3.03e-02	23
GO:0062197111	Esophagus	ESCC	cellular response to chemical stress	234/8552	337/18723	5.37e-19	5.97e-17	234
GO:007121419	Esophagus	ESCC	cellular response to abiotic stimulus	206/8552	331/18723	7.52e-10	1.88e-08	206
GO:010400419	Esophagus	ESCC	cellular response to environmental stimulus	206/8552	331/18723	7.52e-10	1.88e-08	206
GO:00069707	Esophagus	ESCC	response to osmotic stress	57/8552	84/18723	3.26e-05	2.70e-04	57
GO:00714707	Esophagus	ESCC	cellular response to osmotic stress	31/8552	41/18723	9.32e-05	6.68e-04	31
GO:00512623	Esophagus	ESCC	protein tetramerization	54/8552	87/18723	1.50e-03	7.06e-03	54
GO:0006971	Esophagus	ESCC	hypotonic response	10/8552	11/18723	2.54e-03	1.08e-02	10
GO:00512592	Esophagus	ESCC	protein complex oligomerization	130/8552	238/18723	3.29e-03	1.36e-02	130
GO:006219720	Oral cavity	OSCC	cellular response to chemical stress	204/7305	337/18723	6.89e-16	5.19e-14	204
GO:007121416	Oral cavity	OSCC	cellular response to abiotic stimulus	186/7305	331/18723	1.38e-10	4.10e-09	186

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa049704	Breast	IDC	Salivary secretion	18/867	93/8465	5.69e-03	3.13e-02	2.34e-02	18
hsa0497011	Breast	IDC	Salivary secretion	18/867	93/8465	5.69e-03	3.13e-02	2.34e-02	18

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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

AQP5

SNV

Missense_Mutation

c.301G>A

p.Gly101Arg

p.G101R

P55064

protein_coding

deleterious(0.03)

probably_damaging(0.998)

TCGA-A7-A26H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

AQP5

SNV

Missense_Mutation

c.92N>G

p.Ser31Trp

p.S31W

P55064

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-E2-A152-01

Breast

breast invasive carcinoma

Female

<65

I/II

Targeted Molecular therapy

trastuzumab

AQP5

insertion

In_Frame_Ins

novel

c.702_703insGTG

p.Glu234_Arg235insVal

p.E234_R235insV

P55064

protein_coding

TCGA-A8-A09D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

AQP5

insertion

Nonsense_Mutation

novel

c.730_731insCACTTCAGATGGATGAGTCCAGCAGAGTTTA

p.Glu244AlafsTer11

p.E244Afs*11

P55064

protein_coding

TCGA-A8-A0A4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

AQP5

SNV

Missense_Mutation

c.226C>T

p.Leu76Phe

p.L76F

P55064

protein_coding

tolerated(1)

benign(0.035)

TCGA-EA-A6QX-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

AQP5

SNV

Missense_Mutation

novel

c.197G>T

p.Gly66Val

p.G66V

P55064

protein_coding

deleterious(0.01)

probably_damaging(0.977)

TCGA-ZJ-AAX4-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

AQP5

SNV

Missense_Mutation

novel

c.46N>A

p.Ala16Thr

p.A16T

P55064

protein_coding

tolerated(0.05)

probably_damaging(0.925)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

AQP5

SNV

Missense_Mutation

c.766N>T

p.Arg256Trp

p.R256W

P55064

protein_coding

deleterious(0)

possibly_damaging(0.857)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

AQP5

SNV

Missense_Mutation

novel

c.161N>A

p.Gly54Asp

p.G54D

P55064

protein_coding

deleterious(0)

possibly_damaging(0.684)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

AQP5

SNV

Missense_Mutation

novel

c.286G>A

p.Val96Met

p.V96M

P55064

protein_coding

deleterious(0.01)

benign(0.438)

TCGA-B5-A1MX-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Hormone Therapy

megace

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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
362	AQP5	ION CHANNEL, TRANSPORTER	inhibitor	178101032

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