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: PDE4B

Gene summary for PDE4B

Gene summary.

Gene information	Species	Human
	Gene symbol	PDE4B
	Gene ID	5142
	Gene name	phosphodiesterase 4B
	Gene Alias	DPDE4
	Cytomap	1p31.3
	Gene Type	protein-coding
	GO ID	GO:0001776
	UniProtAcc	Q07343

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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
5142	PDE4B	LZE7T	Human	Esophagus	ESCC	4.58e-03	3.97e-01	0.0667
5142	PDE4B	LZE6T	Human	Esophagus	ESCC	8.22e-06	5.41e-01	0.0845
5142	PDE4B	P2T-E	Human	Esophagus	ESCC	6.25e-43	1.66e+00	0.1177
5142	PDE4B	P10T-E	Human	Esophagus	ESCC	9.39e-20	6.10e-01	0.116
5142	PDE4B	P16T-E	Human	Esophagus	ESCC	8.79e-14	3.61e-01	0.1153
5142	PDE4B	P32T-E	Human	Esophagus	ESCC	3.69e-05	3.34e-01	0.1666
5142	PDE4B	P36T-E	Human	Esophagus	ESCC	3.98e-02	1.28e-01	0.1187
5142	PDE4B	P48T-E	Human	Esophagus	ESCC	2.65e-03	3.36e-01	0.0959
5142	PDE4B	P56T-E	Human	Esophagus	ESCC	1.21e-10	1.90e+00	0.1613
5142	PDE4B	P76T-E	Human	Esophagus	ESCC	5.42e-26	9.95e-01	0.1207
5142	PDE4B	P130T-E	Human	Esophagus	ESCC	6.32e-03	3.58e-01	0.1676
5142	PDE4B	C04	Human	Oral cavity	OSCC	7.20e-05	4.81e-01	0.2633
5142	PDE4B	C43	Human	Oral cavity	OSCC	9.93e-08	2.30e-01	0.1704
5142	PDE4B	C08	Human	Oral cavity	OSCC	1.28e-06	3.06e-01	0.1919
5142	PDE4B	C09	Human	Oral cavity	OSCC	1.73e-06	5.12e-01	0.1431
5142	PDE4B	EOLP-1	Human	Oral cavity	EOLP	1.26e-25	9.04e-01	-0.0202
5142	PDE4B	NEOLP-1	Human	Oral cavity	NEOLP	2.25e-06	2.51e-01	-0.0194
5142	PDE4B	GSM5252126_BPH283PrGF_Via	Human	Prostate	BPH	3.04e-04	4.73e-01	-0.1771
5142	PDE4B	GSM5252127_BPH283PrSF_Via	Human	Prostate	BPH	3.61e-06	5.91e-01	-0.1453
5142	PDE4B	GSM5252128_BPH327PrGF_Via	Human	Prostate	BPH	3.57e-04	3.13e-01	-0.1688

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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
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
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:0034655110	Esophagus	ESCC	nucleobase-containing compound catabolic process	272/8552	407/18723	2.92e-18	2.90e-16	272
GO:004670018	Esophagus	ESCC	heterocycle catabolic process	286/8552	445/18723	1.12e-15	7.47e-14	286
GO:004427019	Esophagus	ESCC	cellular nitrogen compound catabolic process	288/8552	451/18723	3.03e-15	1.79e-13	288
GO:001943918	Esophagus	ESCC	aromatic compound catabolic process	295/8552	467/18723	1.09e-14	5.98e-13	295
GO:190136118	Esophagus	ESCC	organic cyclic compound catabolic process	307/8552	495/18723	9.99e-14	4.80e-12	307
GO:0006753110	Esophagus	ESCC	nucleoside phosphate metabolic process	288/8552	497/18723	1.80e-08	3.50e-07	288
GO:0019693111	Esophagus	ESCC	ribose phosphate metabolic process	234/8552	396/18723	4.24e-08	7.76e-07	234
GO:0009117111	Esophagus	ESCC	nucleotide metabolic process	282/8552	489/18723	4.70e-08	8.50e-07	282
GO:0002262111	Esophagus	ESCC	myeloid cell homeostasis	104/8552	157/18723	1.49e-07	2.36e-06	104
GO:0032970111	Esophagus	ESCC	regulation of actin filament-based process	231/8552	397/18723	2.91e-07	4.20e-06	231
GO:0009259111	Esophagus	ESCC	ribonucleotide metabolic process	224/8552	385/18723	4.41e-07	6.00e-06	224
GO:0072521111	Esophagus	ESCC	purine-containing compound metabolic process	238/8552	416/18723	1.20e-06	1.49e-05	238
GO:0048872111	Esophagus	ESCC	homeostasis of number of cells	163/8552	272/18723	1.40e-06	1.69e-05	163
GO:0009150111	Esophagus	ESCC	purine ribonucleotide metabolic process	213/8552	368/18723	1.40e-06	1.69e-05	213
GO:0006163111	Esophagus	ESCC	purine nucleotide metabolic process	226/8552	396/18723	2.81e-06	3.21e-05	226
GO:000941020	Esophagus	ESCC	response to xenobiotic stimulus	253/8552	462/18723	4.55e-05	3.58e-04	253
GO:003249619	Esophagus	ESCC	response to lipopolysaccharide	191/8552	343/18723	1.11e-04	7.73e-04	191
GO:19011362	Esophagus	ESCC	carbohydrate derivative catabolic process	99/8552	172/18723	1.11e-03	5.54e-03	99
GO:00508528	Esophagus	ESCC	T cell receptor signaling pathway	73/8552	123/18723	1.54e-03	7.24e-03	73
GO:000223719	Esophagus	ESCC	response to molecule of bacterial origin	194/8552	363/18723	1.64e-03	7.61e-03	194

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0492816	Esophagus	ESCC	Parathyroid hormone synthesis, secretion and action	66/4205	106/8465	5.86e-03	1.47e-02	7.51e-03	66
hsa0492817	Esophagus	ESCC	Parathyroid hormone synthesis, secretion and action	66/4205	106/8465	5.86e-03	1.47e-02	7.51e-03	66
hsa0492814	Prostate	BPH	Parathyroid hormone synthesis, secretion and action	33/1718	106/8465	5.30e-03	1.75e-02	1.08e-02	33
hsa0492815	Prostate	BPH	Parathyroid hormone synthesis, secretion and action	33/1718	106/8465	5.30e-03	1.75e-02	1.08e-02	33
hsa0492822	Prostate	Tumor	Parathyroid hormone synthesis, secretion and action	35/1791	106/8465	2.89e-03	1.07e-02	6.67e-03	35
hsa0492832	Prostate	Tumor	Parathyroid hormone synthesis, secretion and action	35/1791	106/8465	2.89e-03	1.07e-02	6.67e-03	35

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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

PDE4B

SNV

Missense_Mutation

c.220N>T

p.Pro74Ser

p.P74S

Q07343

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.968)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PDE4B

SNV

Missense_Mutation

c.2031G>C

p.Lys677Asn

p.K677N

Q07343

protein_coding

deleterious(0.02)

probably_damaging(0.953)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PDE4B

SNV

Missense_Mutation

novel

c.936G>T

p.Lys312Asn

p.K312N

Q07343

protein_coding

deleterious(0.02)

possibly_damaging(0.821)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PDE4B

SNV

Missense_Mutation

novel

c.355G>T

p.Val119Leu

p.V119L

Q07343

protein_coding

deleterious(0.02)

benign(0.133)

TCGA-AN-A0FX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PDE4B

SNV

Missense_Mutation

c.1534G>A

p.Asp512Asn

p.D512N

Q07343

protein_coding

deleterious(0.01)

probably_damaging(0.931)

TCGA-AO-A1KR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

PDE4B

SNV

Missense_Mutation

novel

c.1124N>C

p.Arg375Thr

p.R375T

Q07343

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PDE4B

SNV

Missense_Mutation

c.72N>C

p.Leu24Phe

p.L24F

Q07343

protein_coding

tolerated_low_confidence(0.72)

probably_damaging(0.969)

TCGA-BH-A1FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PDE4B

SNV

Missense_Mutation

c.1865N>C

p.Ile622Thr

p.I622T

Q07343

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-C8-A12U-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PDE4B

SNV

Missense_Mutation

c.2007N>T

p.Arg669Ser

p.R669S

Q07343

protein_coding

tolerated_low_confidence(0.66)

benign(0.006)

TCGA-D8-A147-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

PDE4B

SNV

Missense_Mutation

rs752491251

c.1741C>T

p.Arg581Cys

p.R581C

Q07343

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-D8-A1XQ-01

Breast

breast invasive 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
5142	PDE4B	DRUGGABLE GENOME, ENZYME		RPL-554
5142	PDE4B	DRUGGABLE GENOME, ENZYME		DYPHYLLINE	DYPHYLLINE
5142	PDE4B	DRUGGABLE GENOME, ENZYME	inhibitor	CHEMBL484785	CRISABOROLE
5142	PDE4B	DRUGGABLE GENOME, ENZYME		APREMILAST	APREMILAST
5142	PDE4B	DRUGGABLE GENOME, ENZYME		RONOMILAST
5142	PDE4B	DRUGGABLE GENOME, ENZYME		THEOPHYLLINE	THEOPHYLLINE
5142	PDE4B	DRUGGABLE GENOME, ENZYME		AN-2728	CRISABOROLE
5142	PDE4B	DRUGGABLE GENOME, ENZYME		DENBUFYLLINE	DENBUFYLLINE
5142	PDE4B	DRUGGABLE GENOME, ENZYME		MEM 1414
5142	PDE4B	DRUGGABLE GENOME, ENZYME		ethanol	ALCOHOL	32451486

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