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: PLD3

Gene summary for PLD3

Gene summary.

Gene information	Species	Human
	Gene symbol	PLD3
	Gene ID	23646
	Gene name	phospholipase D family member 3
	Gene Alias	AD19
	Cytomap	19q13.2
	Gene Type	protein-coding
	GO ID	GO:0001816
	UniProtAcc	A0A024R0Q4

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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
23646	PLD3	CA_HPV_1	Human	Cervix	CC	4.09e-06	-2.07e-01	0.0264
23646	PLD3	CA_HPV_3	Human	Cervix	CC	2.22e-02	3.49e-02	0.0414
23646	PLD3	CCII_1	Human	Cervix	CC	1.99e-02	-3.28e-01	0.3249
23646	PLD3	sample1	Human	Cervix	CC	6.24e-05	5.44e-01	0.0959
23646	PLD3	sample3	Human	Cervix	CC	8.75e-07	2.42e-01	0.1387
23646	PLD3	L1	Human	Cervix	CC	2.23e-02	-2.47e-01	0.0802
23646	PLD3	T1	Human	Cervix	CC	1.32e-15	6.19e-01	0.0918
23646	PLD3	T3	Human	Cervix	CC	2.98e-04	1.37e-01	0.1389
23646	PLD3	AEH-subject1	Human	Endometrium	AEH	1.82e-07	-1.86e-01	-0.3059
23646	PLD3	AEH-subject2	Human	Endometrium	AEH	4.57e-04	-1.83e-01	-0.2525
23646	PLD3	AEH-subject3	Human	Endometrium	AEH	6.20e-10	-2.49e-01	-0.2576
23646	PLD3	AEH-subject4	Human	Endometrium	AEH	3.02e-06	-3.13e-01	-0.2657
23646	PLD3	AEH-subject5	Human	Endometrium	AEH	4.47e-14	-4.18e-01	-0.2953
23646	PLD3	EEC-subject1	Human	Endometrium	EEC	3.36e-08	-2.19e-01	-0.2682
23646	PLD3	EEC-subject2	Human	Endometrium	EEC	1.08e-06	-2.33e-01	-0.2607
23646	PLD3	EEC-subject3	Human	Endometrium	EEC	1.46e-35	-4.07e-01	-0.2525
23646	PLD3	EEC-subject4	Human	Endometrium	EEC	6.79e-03	-2.52e-01	-0.2571
23646	PLD3	EEC-subject5	Human	Endometrium	EEC	4.71e-09	-2.74e-01	-0.249
23646	PLD3	GSM5276934	Human	Endometrium	EEC	2.98e-06	-2.01e-01	-0.0913
23646	PLD3	GSM5276937	Human	Endometrium	EEC	3.14e-12	-4.31e-01	-0.0897

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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:00426924	Cervix	CC	muscle cell differentiation	69/2311	384/18723	8.12e-04	7.09e-03	69
GO:00511464	Cervix	CC	striated muscle cell differentiation	50/2311	283/18723	5.53e-03	3.19e-02	50
GO:00426925	Endometrium	AEH	muscle cell differentiation	68/2100	384/18723	8.88e-05	1.30e-03	68
GO:00511465	Endometrium	AEH	striated muscle cell differentiation	51/2100	283/18723	4.20e-04	4.46e-03	51
GO:004269212	Endometrium	EEC	muscle cell differentiation	67/2168	384/18723	3.87e-04	4.12e-03	67
GO:005114613	Endometrium	EEC	striated muscle cell differentiation	51/2168	283/18723	8.71e-04	7.97e-03	51
GO:00903053	Esophagus	ESCC	nucleic acid phosphodiester bond hydrolysis	163/8552	261/18723	3.07e-08	5.73e-07	163
GO:0090305	Liver	HCC	nucleic acid phosphodiester bond hydrolysis	152/7958	261/18723	1.90e-07	3.46e-06	152
GO:0042692	Lung	IAC	muscle cell differentiation	65/2061	384/18723	2.75e-04	4.54e-03	65
GO:00511462	Lung	IAC	striated muscle cell differentiation	47/2061	283/18723	2.66e-03	2.45e-02	47
GO:00426921	Lung	AIS	muscle cell differentiation	58/1849	384/18723	7.00e-04	1.03e-02	58
GO:00511461	Lung	AIS	striated muscle cell differentiation	42/1849	283/18723	4.88e-03	4.24e-02	42
GO:00426922	Lung	MIAC	muscle cell differentiation	39/967	384/18723	4.51e-05	2.36e-03	39
GO:00903052	Oral cavity	OSCC	nucleic acid phosphodiester bond hydrolysis	142/7305	261/18723	2.90e-07	4.43e-06	142
GO:00426927	Oral cavity	OSCC	muscle cell differentiation	175/7305	384/18723	4.79e-03	1.92e-02	175
GO:00903051	Oral cavity	LP	nucleic acid phosphodiester bond hydrolysis	92/4623	261/18723	8.07e-05	1.04e-03	92
GO:00426926	Prostate	BPH	muscle cell differentiation	88/3107	384/18723	7.59e-04	5.01e-03	88
GO:00511466	Prostate	BPH	striated muscle cell differentiation	62/3107	283/18723	1.15e-02	4.68e-02	62
GO:004269213	Prostate	Tumor	muscle cell differentiation	93/3246	384/18723	3.45e-04	2.73e-03	93
GO:005114614	Prostate	Tumor	striated muscle cell differentiation	69/3246	283/18723	1.56e-03	9.54e-03	69

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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

PLD3

SNV

Missense_Mutation

rs145892029

c.1154N>A

p.Arg385His

p.R385H

Q8IV08

protein_coding

tolerated(0.17)

benign(0)

TCGA-AO-A0JM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PLD3

SNV

Missense_Mutation

c.916N>G

p.Pro306Ala

p.P306A

Q8IV08

protein_coding

tolerated(0.82)

benign(0.005)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

PLD3

SNV

Missense_Mutation

novel

c.931C>G

p.Leu311Val

p.L311V

Q8IV08

protein_coding

tolerated(0.25)

benign(0.079)

TCGA-E9-A3HO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

PLD3

insertion

Frame_Shift_Ins

novel

c.893_894insAG

p.Leu299AlafsTer11

p.L299Afs*11

Q8IV08

protein_coding

TCGA-A7-A26I-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

PLD3

insertion

Frame_Shift_Ins

novel

c.894_895insTTTCTGGT

p.Leu299PhefsTer13

p.L299Ffs*13

Q8IV08

protein_coding

TCGA-A7-A26I-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

PLD3

insertion

Frame_Shift_Ins

novel

c.893_894insAGCTTTCTGGTCT

p.Leu299AlafsTer52

p.L299Afs*52

Q8IV08

protein_coding

TCGA-AC-A3QQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PLD3

insertion

Nonsense_Mutation

novel

c.1090_1091insCTGAGAAGCTTGGCTGGTATGTGAGCAAATAAACGGAACTAT

p.Ile364delinsThrGluLysLeuGlyTrpTyrValSerLysTerThrGluLeuPhe

p.I364delinsTEKLGWYVSK*TELF

Q8IV08

protein_coding

TCGA-BH-A0E2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

PLD3

insertion

Frame_Shift_Ins

novel

c.19_20insCCAGCCTGGGCAAAAGAGCGAA

p.Tyr7SerfsTer21

p.Y7Sfs*21

Q8IV08

protein_coding

TCGA-BH-A0HQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

PLD3

insertion

Frame_Shift_Ins

novel

c.21_22insT

p.Gln8SerfsTer13

p.Q8Sfs*13

Q8IV08

protein_coding

TCGA-BH-A0HQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

PLD3

SNV

Missense_Mutation

novel

c.95N>T

p.Ala32Val

p.A32V

Q8IV08

protein_coding

deleterious_low_confidence(0.04)

benign(0.006)

TCGA-2W-A8YY-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

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