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: PLCD1

Gene summary for PLCD1

Gene summary.

Gene information	Species	Human
	Gene symbol	PLCD1
	Gene ID	5333
	Gene name	phospholipase C delta 1
	Gene Alias	NDNC3
	Cytomap	3p22.2
	Gene Type	protein-coding
	GO ID	GO:0006629
	UniProtAcc	P51178

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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
5333	PLCD1	HTA11_2487_2000001011	Human	Colorectum	SER	1.64e-03	2.48e-01	-0.1808
5333	PLCD1	HTA11_347_2000001011	Human	Colorectum	AD	5.45e-09	3.38e-01	-0.1954
5333	PLCD1	HTA11_696_2000001011	Human	Colorectum	AD	7.62e-09	3.71e-01	-0.1464
5333	PLCD1	HTA11_1391_2000001011	Human	Colorectum	AD	6.12e-04	2.32e-01	-0.059
5333	PLCD1	HTA11_2992_2000001011	Human	Colorectum	SER	9.96e-04	3.44e-01	-0.1706
5333	PLCD1	HTA11_5212_2000001011	Human	Colorectum	AD	5.92e-06	4.51e-01	-0.2061
5333	PLCD1	CRC-1-8810	Human	Colorectum	CRC	8.13e-03	-9.59e-02	0.6257
5333	PLCD1	LZE7T	Human	Esophagus	ESCC	1.14e-03	2.93e-01	0.0667
5333	PLCD1	LZE24T	Human	Esophagus	ESCC	3.63e-05	8.50e-02	0.0596
5333	PLCD1	P2T-E	Human	Esophagus	ESCC	9.66e-07	3.57e-02	0.1177
5333	PLCD1	P4T-E	Human	Esophagus	ESCC	2.65e-10	1.32e-01	0.1323
5333	PLCD1	P5T-E	Human	Esophagus	ESCC	8.39e-04	1.58e-02	0.1327
5333	PLCD1	P12T-E	Human	Esophagus	ESCC	5.95e-14	2.04e-01	0.1122
5333	PLCD1	P16T-E	Human	Esophagus	ESCC	1.31e-05	2.43e-02	0.1153
5333	PLCD1	P20T-E	Human	Esophagus	ESCC	1.54e-02	4.39e-02	0.1124
5333	PLCD1	P21T-E	Human	Esophagus	ESCC	4.58e-09	1.52e-01	0.1617
5333	PLCD1	P22T-E	Human	Esophagus	ESCC	8.82e-09	4.48e-02	0.1236
5333	PLCD1	P24T-E	Human	Esophagus	ESCC	9.73e-05	8.20e-02	0.1287
5333	PLCD1	P26T-E	Human	Esophagus	ESCC	5.20e-04	6.96e-02	0.1276
5333	PLCD1	P27T-E	Human	Esophagus	ESCC	3.51e-06	6.90e-02	0.1055

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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

∗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:0016042	Colorectum	AD	lipid catabolic process	97/3918	320/18723	4.31e-05	7.56e-04	97
GO:0048017	Colorectum	AD	inositol lipid-mediated signaling	53/3918	182/18723	5.35e-03	3.52e-02	53
GO:0048015	Colorectum	AD	phosphatidylinositol-mediated signaling	52/3918	178/18723	5.37e-03	3.54e-02	52
GO:0006650	Colorectum	AD	glycerophospholipid metabolic process	83/3918	306/18723	5.40e-03	3.55e-02	83
GO:0006644	Colorectum	AD	phospholipid metabolic process	101/3918	383/18723	5.80e-03	3.67e-02	101
GO:00160421	Colorectum	SER	lipid catabolic process	77/2897	320/18723	3.52e-05	9.18e-04	77
GO:0046486	Colorectum	SER	glycerolipid metabolic process	82/2897	392/18723	2.26e-03	2.17e-02	82
GO:00066441	Colorectum	SER	phospholipid metabolic process	79/2897	383/18723	3.94e-03	3.24e-02	79
GO:00480171	Colorectum	SER	inositol lipid-mediated signaling	42/2897	182/18723	4.36e-03	3.49e-02	42
GO:00480151	Colorectum	SER	phosphatidylinositol-mediated signaling	41/2897	178/18723	4.97e-03	3.86e-02	41
GO:00066501	Colorectum	SER	glycerophospholipid metabolic process	64/2897	306/18723	6.41e-03	4.60e-02	64
GO:00066503	Colorectum	CRC	glycerophospholipid metabolic process	55/2078	306/18723	2.10e-04	3.55e-03	55
GO:00066443	Colorectum	CRC	phospholipid metabolic process	65/2078	383/18723	3.21e-04	4.95e-03	65
GO:00464861	Colorectum	CRC	glycerolipid metabolic process	64/2078	392/18723	1.01e-03	1.19e-02	64
GO:00160424	Colorectum	CRC	lipid catabolic process	53/2078	320/18723	1.89e-03	1.93e-02	53
GO:00066446	Esophagus	ESCC	phospholipid metabolic process	218/8552	383/18723	5.37e-06	5.59e-05	218
GO:00066505	Esophagus	ESCC	glycerophospholipid metabolic process	174/8552	306/18723	4.92e-05	3.85e-04	174
GO:00464864	Esophagus	ESCC	glycerolipid metabolic process	211/8552	392/18723	6.51e-04	3.46e-03	211
GO:00160427	Esophagus	ESCC	lipid catabolic process	168/8552	320/18723	7.97e-03	2.84e-02	168

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05131	Colorectum	AD	Shigellosis	109/2092	247/8465	1.09e-11	2.44e-10	1.55e-10	109
hsa04919	Colorectum	AD	Thyroid hormone signaling pathway	51/2092	121/8465	1.71e-05	1.73e-04	1.10e-04	51
hsa051311	Colorectum	AD	Shigellosis	109/2092	247/8465	1.09e-11	2.44e-10	1.55e-10	109
hsa049191	Colorectum	AD	Thyroid hormone signaling pathway	51/2092	121/8465	1.71e-05	1.73e-04	1.10e-04	51
hsa051312	Colorectum	SER	Shigellosis	87/1580	247/8465	3.07e-10	7.27e-09	5.28e-09	87
hsa049192	Colorectum	SER	Thyroid hormone signaling pathway	40/1580	121/8465	1.02e-04	1.06e-03	7.67e-04	40
hsa051313	Colorectum	SER	Shigellosis	87/1580	247/8465	3.07e-10	7.27e-09	5.28e-09	87
hsa049193	Colorectum	SER	Thyroid hormone signaling pathway	40/1580	121/8465	1.02e-04	1.06e-03	7.67e-04	40
hsa0513110	Colorectum	CRC	Shigellosis	59/1091	247/8465	1.19e-06	5.41e-05	3.66e-05	59
hsa0491910	Colorectum	CRC	Thyroid hormone signaling pathway	35/1091	121/8465	2.05e-06	6.85e-05	4.64e-05	35
hsa04070	Colorectum	CRC	Phosphatidylinositol signaling system	25/1091	97/8465	4.27e-04	4.60e-03	3.12e-03	25
hsa00562	Colorectum	CRC	Inositol phosphate metabolism	18/1091	73/8465	4.38e-03	2.52e-02	1.71e-02	18
hsa049332	Colorectum	CRC	AGE-RAGE signaling pathway in diabetic complications	22/1091	100/8465	7.59e-03	3.67e-02	2.49e-02	22
hsa0513111	Colorectum	CRC	Shigellosis	59/1091	247/8465	1.19e-06	5.41e-05	3.66e-05	59
hsa0491911	Colorectum	CRC	Thyroid hormone signaling pathway	35/1091	121/8465	2.05e-06	6.85e-05	4.64e-05	35
hsa040701	Colorectum	CRC	Phosphatidylinositol signaling system	25/1091	97/8465	4.27e-04	4.60e-03	3.12e-03	25
hsa005621	Colorectum	CRC	Inositol phosphate metabolism	18/1091	73/8465	4.38e-03	2.52e-02	1.71e-02	18
hsa049333	Colorectum	CRC	AGE-RAGE signaling pathway in diabetic complications	22/1091	100/8465	7.59e-03	3.67e-02	2.49e-02	22
hsa05131211	Esophagus	ESCC	Shigellosis	176/4205	247/8465	2.27e-12	4.01e-11	2.05e-11	176
hsa0493310	Esophagus	ESCC	AGE-RAGE signaling pathway in diabetic complications	72/4205	100/8465	4.15e-06	2.28e-05	1.17e-05	72

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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

PLCD1

SNV

Missense_Mutation

rs774417743

c.181N>T

p.Arg61Cys

p.R61C

P51178

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-B6-A0WT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PLCD1

SNV

Missense_Mutation

c.91N>T

p.Arg31Trp

p.R31W

P51178

protein_coding

deleterious(0)

possibly_damaging(0.598)

TCGA-E9-A1NA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

PLCD1

SNV

Missense_Mutation

novel

c.913N>T

p.Gly305Cys

p.G305C

P51178

protein_coding

deleterious(0)

probably_damaging(0.92)

TCGA-PL-A8LZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

PLCD1

deletion

In_Frame_Del

c.1316_1327delNNNNNNNNNNNN

p.Leu439_Thr443delinsPro

p.L439_T443delinsP

P51178

protein_coding

TCGA-C8-A138-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

PLCD1

SNV

Missense_Mutation

novel

c.1114N>A

p.Glu372Lys

p.E372K

P51178

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-C5-A902-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PLCD1

SNV

Missense_Mutation

novel

c.520G>A

p.Asp174Asn

p.D174N

P51178

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

PLCD1

SNV

Missense_Mutation

c.1348G>C

p.Glu450Gln

p.E450Q

P51178

protein_coding

tolerated(0.07)

probably_damaging(0.951)

TCGA-MY-A5BD-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PLCD1

SNV

Missense_Mutation

rs779608157

c.1916G>A

p.Arg639His

p.R639H

P51178

protein_coding

tolerated(0.08)

benign(0.146)

TCGA-VS-A9UL-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Unknown

PLCD1

SNV

Missense_Mutation

rs769966321

c.787N>T

p.Arg263Trp

p.R263W

P51178

protein_coding

deleterious(0.02)

possibly_damaging(0.773)

TCGA-AA-3941-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PLCD1

SNV

Missense_Mutation

novel

c.182G>A

p.Arg61His

p.R61H

P51178

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AA-3949-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

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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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