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: PHIP

Gene summary for PHIP

Gene summary.

Gene information	Species	Human
	Gene symbol	PHIP
	Gene ID	55023
	Gene name	pleckstrin homology domain interacting protein
	Gene Alias	BRWD2
	Cytomap	6q14.1
	Gene Type	protein-coding
	GO ID	GO:0000278
	UniProtAcc	Q8WWQ0

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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
55023	PHIP	CA_HPV_1	Human	Cervix	CC	1.96e-05	-8.89e-02	0.0264
55023	PHIP	CCI_1	Human	Cervix	CC	5.91e-03	6.57e-01	0.528
55023	PHIP	CCI_2	Human	Cervix	CC	4.54e-09	6.65e-01	0.5249
55023	PHIP	CCI_3	Human	Cervix	CC	8.57e-07	9.79e-01	0.516
55023	PHIP	L1	Human	Cervix	CC	1.75e-04	-1.30e-01	0.0802
55023	PHIP	HTA11_3410_2000001011	Human	Colorectum	AD	6.25e-18	-7.22e-01	0.0155
55023	PHIP	HTA11_2487_2000001011	Human	Colorectum	SER	1.73e-08	-7.27e-01	-0.1808
55023	PHIP	HTA11_2951_2000001011	Human	Colorectum	AD	4.29e-03	-8.68e-01	0.0216
55023	PHIP	HTA11_3361_2000001011	Human	Colorectum	AD	5.05e-04	-6.48e-01	-0.1207
55023	PHIP	HTA11_696_2000001011	Human	Colorectum	AD	5.92e-22	-6.24e-01	-0.1464
55023	PHIP	HTA11_866_2000001011	Human	Colorectum	AD	5.20e-07	-4.56e-01	-0.1001
55023	PHIP	HTA11_7862_2000001011	Human	Colorectum	AD	9.88e-06	-8.07e-01	-0.0179
55023	PHIP	HTA11_866_3004761011	Human	Colorectum	AD	3.95e-12	-6.75e-01	0.096
55023	PHIP	HTA11_9408_2000001011	Human	Colorectum	AD	8.33e-03	-9.26e-01	0.0451
55023	PHIP	HTA11_8622_2000001021	Human	Colorectum	SER	4.42e-02	-6.41e-01	0.0528
55023	PHIP	HTA11_10711_2000001011	Human	Colorectum	AD	4.24e-06	-6.65e-01	0.0338
55023	PHIP	HTA11_7696_3000711011	Human	Colorectum	AD	9.14e-18	-5.79e-01	0.0674
55023	PHIP	HTA11_6818_2000001021	Human	Colorectum	AD	4.82e-06	-5.49e-01	0.0588
55023	PHIP	HTA11_99999970781_79442	Human	Colorectum	MSS	2.26e-13	-5.31e-01	0.294
55023	PHIP	HTA11_99999971662_82457	Human	Colorectum	MSS	2.25e-05	-3.75e-01	0.3859

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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
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
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:000836025	Skin	cSCC	regulation of cell shape	57/4864	154/18723	1.61e-03	9.90e-03	57
GO:200123727	Skin	cSCC	negative regulation of extrinsic apoptotic signaling pathway	38/4864	97/18723	2.95e-03	1.64e-02	38
GO:000828616	Skin	cSCC	insulin receptor signaling pathway	43/4864	116/18723	5.44e-03	2.73e-02	43
GO:2001233113	Thyroid	PTC	regulation of apoptotic signaling pathway	197/5968	356/18723	2.58e-20	3.69e-18	197
GO:0022604112	Thyroid	PTC	regulation of cell morphogenesis	165/5968	309/18723	2.60e-15	1.82e-13	165
GO:2001234113	Thyroid	PTC	negative regulation of apoptotic signaling pathway	124/5968	224/18723	2.57e-13	1.32e-11	124
GO:0097191113	Thyroid	PTC	extrinsic apoptotic signaling pathway	117/5968	219/18723	2.73e-11	1.03e-09	117
GO:000734619	Thyroid	PTC	regulation of mitotic cell cycle	212/5968	457/18723	4.03e-11	1.44e-09	212
GO:0008360111	Thyroid	PTC	regulation of cell shape	86/5968	154/18723	6.22e-10	1.95e-08	86
GO:1901653111	Thyroid	PTC	cellular response to peptide	169/5968	359/18723	9.81e-10	2.89e-08	169
GO:0043434113	Thyroid	PTC	response to peptide hormone	188/5968	414/18723	4.13e-09	1.09e-07	188
GO:2001236113	Thyroid	PTC	regulation of extrinsic apoptotic signaling pathway	82/5968	151/18723	9.01e-09	2.18e-07	82
GO:01400148	Thyroid	PTC	mitotic nuclear division	135/5968	287/18723	4.90e-08	1.04e-06	135
GO:0071375110	Thyroid	PTC	cellular response to peptide hormone stimulus	136/5968	290/18723	5.49e-08	1.17e-06	136
GO:004578718	Thyroid	PTC	positive regulation of cell cycle	144/5968	313/18723	9.93e-08	1.99e-06	144
GO:0032869111	Thyroid	PTC	cellular response to insulin stimulus	100/5968	203/18723	1.70e-07	3.19e-06	100
GO:0032868111	Thyroid	PTC	response to insulin	124/5968	264/18723	1.87e-07	3.47e-06	124
GO:2001237113	Thyroid	PTC	negative regulation of extrinsic apoptotic signaling pathway	51/5968	97/18723	1.83e-05	1.88e-04	51
GO:000828617	Thyroid	PTC	insulin receptor signaling pathway	58/5968	116/18723	3.59e-05	3.36e-04	58
GO:009006816	Thyroid	PTC	positive regulation of cell cycle process	103/5968	236/18723	9.03e-05	7.50e-04	103

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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

PHIP

SNV

Missense_Mutation

novel

c.4808N>T

p.Ser1603Leu

p.S1603L

Q8WWQ0

protein_coding

tolerated_low_confidence(0.27)

benign(0.154)

TCGA-AO-A03P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

PHIP

SNV

Missense_Mutation

rs200729688

c.4529N>A

p.Arg1510Gln

p.R1510Q

Q8WWQ0

protein_coding

tolerated_low_confidence(0.08)

benign(0.388)

TCGA-AO-A0J5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate

zoledronic

PHIP

SNV

Missense_Mutation

rs754515374

c.4120N>G

p.Asn1374Asp

p.N1374D

Q8WWQ0

protein_coding

deleterious(0.03)

benign(0.003)

TCGA-B6-A1KF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PHIP

SNV

Missense_Mutation

c.3457N>A

p.Asp1153Asn

p.D1153N

Q8WWQ0

protein_coding

deleterious(0.04)

benign(0.321)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

PHIP

SNV

Missense_Mutation

c.2326N>A

p.Ala776Thr

p.A776T

Q8WWQ0

protein_coding

tolerated(0.63)

benign(0)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PHIP

SNV

Missense_Mutation

c.3929G>A

p.Arg1310His

p.R1310H

Q8WWQ0

protein_coding

deleterious(0.01)

probably_damaging(0.987)

TCGA-BH-A5IZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PHIP

SNV

Missense_Mutation

c.3754N>A

p.Val1252Met

p.V1252M

Q8WWQ0

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-BH-A6R8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PHIP

SNV

Missense_Mutation

c.2887N>A

p.Glu963Lys

p.E963K

Q8WWQ0

protein_coding

deleterious(0)

benign(0.07)

TCGA-C8-A12T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PHIP

SNV

Missense_Mutation

c.1292N>A

p.Ala431Asp

p.A431D

Q8WWQ0

protein_coding

deleterious(0)

possibly_damaging(0.908)

TCGA-E9-A1RF-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

PHIP

SNV

Missense_Mutation

c.4031N>G

p.Pro1344Arg

p.P1344R

Q8WWQ0

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-GM-A2DH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

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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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