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: PDZD11

Gene summary for PDZD11

Gene summary.

Gene information	Species	Human
	Gene symbol	PDZD11
	Gene ID	51248
	Gene name	PDZ domain containing 11
	Gene Alias	AIPP1
	Cytomap	Xq13.1
	Gene Type	protein-coding
	GO ID	GO:0001505
	UniProtAcc	Q5EBL8

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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
51248	PDZD11	LZE2T	Human	Esophagus	ESCC	3.55e-02	3.89e-01	0.082
51248	PDZD11	LZE4T	Human	Esophagus	ESCC	1.88e-13	2.37e-01	0.0811
51248	PDZD11	LZE5T	Human	Esophagus	ESCC	2.27e-05	3.15e-01	0.0514
51248	PDZD11	LZE7T	Human	Esophagus	ESCC	1.81e-06	6.73e-01	0.0667
51248	PDZD11	LZE8T	Human	Esophagus	ESCC	2.64e-10	1.29e-01	0.067
51248	PDZD11	LZE20T	Human	Esophagus	ESCC	8.35e-09	2.45e-01	0.0662
51248	PDZD11	LZE22T	Human	Esophagus	ESCC	1.68e-07	5.91e-01	0.068
51248	PDZD11	LZE24T	Human	Esophagus	ESCC	3.81e-28	9.88e-01	0.0596
51248	PDZD11	LZE21T	Human	Esophagus	ESCC	2.20e-02	5.49e-01	0.0655
51248	PDZD11	LZE6T	Human	Esophagus	ESCC	1.94e-08	5.59e-01	0.0845
51248	PDZD11	P1T-E	Human	Esophagus	ESCC	5.40e-15	6.37e-01	0.0875
51248	PDZD11	P2T-E	Human	Esophagus	ESCC	3.46e-35	8.24e-01	0.1177
51248	PDZD11	P4T-E	Human	Esophagus	ESCC	9.04e-25	6.73e-01	0.1323
51248	PDZD11	P5T-E	Human	Esophagus	ESCC	4.81e-23	6.25e-01	0.1327
51248	PDZD11	P8T-E	Human	Esophagus	ESCC	2.36e-41	8.46e-01	0.0889
51248	PDZD11	P9T-E	Human	Esophagus	ESCC	4.10e-24	6.13e-01	0.1131
51248	PDZD11	P10T-E	Human	Esophagus	ESCC	1.19e-16	3.00e-01	0.116
51248	PDZD11	P11T-E	Human	Esophagus	ESCC	9.50e-19	7.86e-01	0.1426
51248	PDZD11	P12T-E	Human	Esophagus	ESCC	1.01e-41	8.33e-01	0.1122
51248	PDZD11	P15T-E	Human	Esophagus	ESCC	8.79e-28	6.46e-01	0.1149

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:199077819	Esophagus	ESCC	protein localization to cell periphery	217/8552	333/18723	4.08e-13	1.88e-11	217
GO:000716320	Esophagus	ESCC	establishment or maintenance of cell polarity	143/8552	218/18723	2.05e-09	4.65e-08	143
GO:00469316	Esophagus	ESCC	pore complex assembly	16/8552	20/18723	1.85e-03	8.40e-03	16
GO:00350888	Esophagus	ESCC	establishment or maintenance of apical/basal cell polarity	32/8552	49/18723	4.39e-03	1.73e-02	32
GO:00612458	Esophagus	ESCC	establishment or maintenance of bipolar cell polarity	32/8552	49/18723	4.39e-03	1.73e-02	32
GO:00451978	Esophagus	ESCC	establishment or maintenance of epithelial cell apical/basal polarity	29/8552	44/18723	5.41e-03	2.02e-02	29
GO:199077811	Liver	Cirrhotic	protein localization to cell periphery	135/4634	333/18723	1.18e-10	6.21e-09	135
GO:000716312	Liver	Cirrhotic	establishment or maintenance of cell polarity	82/4634	218/18723	1.55e-05	2.11e-04	82
GO:0046931	Liver	Cirrhotic	pore complex assembly	12/4634	20/18723	8.43e-04	6.12e-03	12
GO:199077821	Liver	HCC	protein localization to cell periphery	200/7958	333/18723	6.07e-11	2.23e-09	200
GO:000716322	Liver	HCC	establishment or maintenance of cell polarity	133/7958	218/18723	2.48e-08	5.73e-07	133
GO:00469311	Liver	HCC	pore complex assembly	17/7958	20/18723	1.18e-04	9.87e-04	17
GO:199077816	Oral cavity	OSCC	protein localization to cell periphery	190/7305	333/18723	1.46e-11	5.13e-10	190
GO:000716318	Oral cavity	OSCC	establishment or maintenance of cell polarity	129/7305	218/18723	1.16e-09	2.86e-08	129
GO:00469315	Oral cavity	OSCC	pore complex assembly	15/7305	20/18723	1.19e-03	5.99e-03	15
GO:199077817	Oral cavity	LP	protein localization to cell periphery	133/4623	333/18723	4.42e-10	2.21e-08	133
GO:000716319	Oral cavity	LP	establishment or maintenance of cell polarity	79/4623	218/18723	8.84e-05	1.11e-03	79
GO:000716327	Skin	cSCC	establishment or maintenance of cell polarity	103/4864	218/18723	9.44e-12	4.85e-10	103
GO:199077824	Skin	cSCC	protein localization to cell periphery	134/4864	333/18723	7.09e-09	2.30e-07	134
GO:003508814	Skin	cSCC	establishment or maintenance of apical/basal cell polarity	26/4864	49/18723	4.78e-05	4.96e-04	26

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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

PDZD11

insertion

Frame_Shift_Ins

novel

c.136_137insATTCTGTGCTCTTGTCTTACAGTTGGGATTTAACATCCGAGGAG

p.Arg46HisfsTer20

p.R46Hfs*20

Q5EBL8

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

PDZD11

insertion

In_Frame_Ins

novel

c.177_178insGATAAGCAGGCCAATCGT

p.Gly59_Phe60insAspLysGlnAlaAsnArg

p.G59_F60insDKQANR

Q5EBL8

protein_coding

TCGA-BH-A0E2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

PDZD11

SNV

Missense_Mutation

rs751113363

c.367N>T

p.Arg123Cys

p.R123C

Q5EBL8

protein_coding

tolerated(0.14)

possibly_damaging(0.465)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PDZD11

SNV

Missense_Mutation

c.188N>A

p.Arg63Gln

p.R63Q

Q5EBL8

protein_coding

tolerated(0.11)

benign(0.003)

TCGA-A6-6781-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

oxaliplatin

PDZD11

SNV

Missense_Mutation

novel

c.98N>G

p.His33Arg

p.H33R

Q5EBL8

protein_coding

tolerated(0.05)

benign(0.047)

TCGA-AA-3811-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

PDZD11

SNV

Missense_Mutation

rs751113363

c.367N>T

p.Arg123Cys

p.R123C

Q5EBL8

protein_coding

tolerated(0.14)

possibly_damaging(0.465)

TCGA-AA-A022-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PDZD11

SNV

Missense_Mutation

novel

c.125N>T

p.Gln42Leu

p.Q42L

Q5EBL8

protein_coding

tolerated(0.08)

benign(0.031)

TCGA-AA-A02R-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PDZD11

SNV

Missense_Mutation

novel

c.323G>A

p.Ser108Asn

p.S108N

Q5EBL8

protein_coding

tolerated(0.12)

benign(0.13)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PDZD11

SNV

Missense_Mutation

c.111C>A

p.Asn37Lys

p.N37K

Q5EBL8

protein_coding

deleterious(0.02)

probably_damaging(0.968)

TCGA-B5-A0JN-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Chemotherapy

paclitaxel

PDZD11

SNV

Missense_Mutation

novel

c.374G>A

p.Arg125His

p.R125H

Q5EBL8

protein_coding

deleterious(0)

possibly_damaging(0.673)

TCGA-B5-A3FA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

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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