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: PHLDB2

Gene summary for PHLDB2

Gene summary.

Gene information	Species	Human
	Gene symbol	PHLDB2
	Gene ID	90102
	Gene name	pleckstrin homology like domain family B member 2
	Gene Alias	LL5b
	Cytomap	3q13.2
	Gene Type	protein-coding
	GO ID	GO:0000226
	UniProtAcc	Q86SQ0

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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
90102	PHLDB2	CCI_1	Human	Cervix	CC	1.53e-03	9.03e-01	0.528
90102	PHLDB2	CCI_3	Human	Cervix	CC	7.19e-05	6.17e-01	0.516
90102	PHLDB2	CCII_1	Human	Cervix	CC	7.87e-06	3.42e-01	0.3249
90102	PHLDB2	sample1	Human	Cervix	CC	3.20e-22	8.14e-01	0.0959
90102	PHLDB2	T1	Human	Cervix	CC	6.64e-45	9.32e-01	0.0918
90102	PHLDB2	LZE4T	Human	Esophagus	ESCC	1.39e-33	1.16e+00	0.0811
90102	PHLDB2	LZE7T	Human	Esophagus	ESCC	6.41e-08	1.60e+00	0.0667
90102	PHLDB2	LZE8T	Human	Esophagus	ESCC	3.86e-08	3.59e-01	0.067
90102	PHLDB2	LZE20T	Human	Esophagus	ESCC	4.68e-02	1.11e-01	0.0662
90102	PHLDB2	LZE21T	Human	Esophagus	ESCC	5.44e-07	3.37e-01	0.0655
90102	PHLDB2	P2T-E	Human	Esophagus	ESCC	5.40e-04	-1.07e-01	0.1177
90102	PHLDB2	P4T-E	Human	Esophagus	ESCC	1.44e-16	7.51e-01	0.1323
90102	PHLDB2	P5T-E	Human	Esophagus	ESCC	1.71e-14	5.23e-01	0.1327
90102	PHLDB2	P9T-E	Human	Esophagus	ESCC	2.88e-34	1.29e+00	0.1131
90102	PHLDB2	P10T-E	Human	Esophagus	ESCC	3.36e-07	2.54e-01	0.116
90102	PHLDB2	P11T-E	Human	Esophagus	ESCC	1.31e-24	1.24e+00	0.1426
90102	PHLDB2	P12T-E	Human	Esophagus	ESCC	3.70e-04	2.27e-01	0.1122
90102	PHLDB2	P15T-E	Human	Esophagus	ESCC	2.04e-23	6.81e-01	0.1149
90102	PHLDB2	P16T-E	Human	Esophagus	ESCC	3.44e-09	5.54e-02	0.1153
90102	PHLDB2	P17T-E	Human	Esophagus	ESCC	2.22e-06	4.54e-01	0.1278

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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
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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:004206010	Cervix	CC	wound healing	109/2311	422/18723	1.84e-14	1.57e-11	109
GO:001081010	Cervix	CC	regulation of cell-substrate adhesion	69/2311	221/18723	8.57e-14	5.69e-11	69
GO:00315898	Cervix	CC	cell-substrate adhesion	96/2311	363/18723	1.48e-13	8.85e-11	96
GO:000701510	Cervix	CC	actin filament organization	109/2311	442/18723	4.92e-13	2.45e-10	109
GO:003297010	Cervix	CC	regulation of actin filament-based process	96/2311	397/18723	4.00e-11	8.54e-09	96
GO:190290310	Cervix	CC	regulation of supramolecular fiber organization	92/2311	383/18723	1.49e-10	2.48e-08	92
GO:01501159	Cervix	CC	cell-substrate junction organization	37/2311	101/18723	3.20e-10	4.46e-08	37
GO:003295610	Cervix	CC	regulation of actin cytoskeleton organization	86/2311	358/18723	5.90e-10	7.51e-08	86
GO:00070448	Cervix	CC	cell-substrate junction assembly	34/2311	95/18723	3.35e-09	3.45e-07	34
GO:00019528	Cervix	CC	regulation of cell-matrix adhesion	40/2311	128/18723	1.32e-08	1.04e-06	40
GO:00071608	Cervix	CC	cell-matrix adhesion	60/2311	233/18723	1.58e-08	1.23e-06	60
GO:00071626	Cervix	CC	negative regulation of cell adhesion	72/2311	303/18723	2.36e-08	1.70e-06	72
GO:011005310	Cervix	CC	regulation of actin filament organization	67/2311	278/18723	4.01e-08	2.54e-06	67
GO:00443193	Cervix	CC	wound healing, spreading of cells	17/2311	34/18723	9.86e-08	5.25e-06	17
GO:00905053	Cervix	CC	epiboly involved in wound healing	17/2311	34/18723	9.86e-08	5.25e-06	17
GO:00905043	Cervix	CC	epiboly	17/2311	35/18723	1.70e-07	7.93e-06	17
GO:006157210	Cervix	CC	actin filament bundle organization	44/2311	161/18723	2.08e-07	9.34e-06	44
GO:005101710	Cervix	CC	actin filament bundle assembly	43/2311	157/18723	2.66e-07	1.12e-05	43
GO:00343298	Cervix	CC	cell junction assembly	88/2311	420/18723	3.42e-07	1.38e-05	88
GO:01501169	Cervix	CC	regulation of cell-substrate junction organization	25/2311	71/18723	5.58e-07	2.06e-05	25

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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

PHLDB2

SNV

Missense_Mutation

c.2706G>T

p.Lys902Asn

p.K902N

Q86SQ0

protein_coding

deleterious(0.02)

possibly_damaging(0.579)

TCGA-AP-A056-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PHLDB2

SNV

Missense_Mutation

c.2172N>A

p.Asp724Glu

p.D724E

Q86SQ0

protein_coding

deleterious(0.02)

probably_damaging(0.925)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PHLDB2

SNV

Missense_Mutation

novel

c.139N>A

p.Leu47Met

p.L47M

Q86SQ0

protein_coding

tolerated_low_confidence(0.09)

probably_damaging(0.942)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

PHLDB2

SNV

Missense_Mutation

c.3119N>T

p.Arg1040Ile

p.R1040I

Q86SQ0

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

PHLDB2

SNV

Missense_Mutation

novel

c.241A>T

p.Ser81Cys

p.S81C

Q86SQ0

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.533)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PHLDB2

SNV

Missense_Mutation

novel

c.1225C>A

p.Leu409Ile

p.L409I

Q86SQ0

protein_coding

tolerated(0.17)

benign(0.001)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PHLDB2

SNV

Missense_Mutation

rs202130294

c.1133N>T

p.Ala378Val

p.A378V

Q86SQ0

protein_coding

tolerated(0.31)

benign(0)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PHLDB2

SNV

Missense_Mutation

c.1706N>T

p.Ser569Ile

p.S569I

Q86SQ0

protein_coding

deleterious(0.01)

benign(0.214)

TCGA-AX-A05Z-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

PHLDB2

SNV

Missense_Mutation

novel

c.953C>T

p.Ala318Val

p.A318V

Q86SQ0

protein_coding

tolerated(0.86)

benign(0)

TCGA-AX-A0J1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PHLDB2

SNV

Missense_Mutation

novel

c.3257N>A

p.Ser1086Asn

p.S1086N

Q86SQ0

protein_coding

tolerated(0.15)

benign(0.05)

TCGA-AX-A1CE-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

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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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