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	P32T-E	Human	Esophagus	ESCC	3.62e-32	7.64e-01	0.1666
55023	PHIP	P36T-E	Human	Esophagus	ESCC	3.50e-28	8.99e-01	0.1187
55023	PHIP	P37T-E	Human	Esophagus	ESCC	8.39e-25	5.72e-01	0.1371
55023	PHIP	P39T-E	Human	Esophagus	ESCC	7.66e-17	3.11e-01	0.0894
55023	PHIP	P40T-E	Human	Esophagus	ESCC	4.45e-09	3.03e-01	0.109
55023	PHIP	P42T-E	Human	Esophagus	ESCC	2.63e-30	8.25e-01	0.1175
55023	PHIP	P44T-E	Human	Esophagus	ESCC	1.70e-16	5.66e-01	0.1096
55023	PHIP	P47T-E	Human	Esophagus	ESCC	2.68e-13	3.23e-01	0.1067
55023	PHIP	P48T-E	Human	Esophagus	ESCC	7.02e-34	9.70e-01	0.0959
55023	PHIP	P49T-E	Human	Esophagus	ESCC	7.71e-10	1.11e+00	0.1768
55023	PHIP	P52T-E	Human	Esophagus	ESCC	1.52e-37	9.73e-01	0.1555
55023	PHIP	P54T-E	Human	Esophagus	ESCC	4.05e-33	7.93e-01	0.0975
55023	PHIP	P56T-E	Human	Esophagus	ESCC	5.75e-10	1.57e+00	0.1613
55023	PHIP	P57T-E	Human	Esophagus	ESCC	2.45e-25	7.55e-01	0.0926
55023	PHIP	P61T-E	Human	Esophagus	ESCC	9.41e-34	9.03e-01	0.099
55023	PHIP	P62T-E	Human	Esophagus	ESCC	6.28e-56	1.02e+00	0.1302
55023	PHIP	P65T-E	Human	Esophagus	ESCC	2.74e-18	3.89e-01	0.0978
55023	PHIP	P74T-E	Human	Esophagus	ESCC	2.10e-39	1.15e+00	0.1479
55023	PHIP	P75T-E	Human	Esophagus	ESCC	3.61e-38	9.35e-01	0.1125
55023	PHIP	P76T-E	Human	Esophagus	ESCC	2.42e-44	9.31e-01	0.1207

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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:200123310	Cervix	CC	regulation of apoptotic signaling pathway	96/2311	356/18723	4.08e-14	3.05e-11	96
GO:002260410	Cervix	CC	regulation of cell morphogenesis	84/2311	309/18723	1.00e-12	4.29e-10	84
GO:200123410	Cervix	CC	negative regulation of apoptotic signaling pathway	56/2311	224/18723	1.39e-07	6.70e-06	56
GO:009719110	Cervix	CC	extrinsic apoptotic signaling pathway	52/2311	219/18723	2.06e-06	6.34e-05	52
GO:00457876	Cervix	CC	positive regulation of cell cycle	66/2311	313/18723	7.78e-06	1.81e-04	66
GO:00073466	Cervix	CC	regulation of mitotic cell cycle	88/2311	457/18723	1.26e-05	2.60e-04	88
GO:00083608	Cervix	CC	regulation of cell shape	38/2311	154/18723	1.86e-05	3.46e-04	38
GO:19016538	Cervix	CC	cellular response to peptide	72/2311	359/18723	1.89e-05	3.48e-04	72
GO:200123610	Cervix	CC	regulation of extrinsic apoptotic signaling pathway	37/2311	151/18723	2.80e-05	4.65e-04	37
GO:00900685	Cervix	CC	positive regulation of cell cycle process	50/2311	236/18723	8.25e-05	1.11e-03	50
GO:00434349	Cervix	CC	response to peptide hormone	77/2311	414/18723	1.40e-04	1.70e-03	77
GO:00713757	Cervix	CC	cellular response to peptide hormone stimulus	57/2311	290/18723	2.32e-04	2.59e-03	57
GO:00328698	Cervix	CC	cellular response to insulin stimulus	42/2311	203/18723	4.95e-04	4.83e-03	42
GO:00328688	Cervix	CC	response to insulin	50/2311	264/18723	1.28e-03	1.02e-02	50
GO:200123710	Cervix	CC	negative regulation of extrinsic apoptotic signaling pathway	23/2311	97/18723	1.39e-03	1.10e-02	23
GO:00082865	Cervix	CC	insulin receptor signaling pathway	25/2311	116/18723	3.59e-03	2.30e-02	25
GO:01400143	Cervix	CC	mitotic nuclear division	50/2311	287/18723	7.27e-03	3.91e-02	50
GO:00482851	Cervix	CC	organelle fission	78/2311	488/18723	9.70e-03	4.79e-02	78
GO:0022604	Colorectum	AD	regulation of cell morphogenesis	109/3918	309/18723	3.08e-09	2.07e-07	109
GO:2001233	Colorectum	AD	regulation of apoptotic signaling pathway	119/3918	356/18723	2.14e-08	1.21e-06	119

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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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