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: DDX21

Gene summary for DDX21

Gene summary.

Gene information	Species	Human
	Gene symbol	DDX21
	Gene ID	9188
	Gene name	DExD-box helicase 21
	Gene Alias	GUA
	Cytomap	10q22.1
	Gene Type	protein-coding
	GO ID	GO:0001503
	UniProtAcc	Q9NR30

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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
9188	DDX21	HTA11_866_2000001011	Human	Colorectum	AD	8.03e-05	-2.38e-01	-0.1001
9188	DDX21	HTA11_99999965104_69814	Human	Colorectum	MSS	2.89e-13	1.01e+00	0.281
9188	DDX21	HTA11_99999971662_82457	Human	Colorectum	MSS	9.39e-08	7.44e-01	0.3859
9188	DDX21	A002-C-010	Human	Colorectum	FAP	6.54e-04	-2.31e-01	0.242
9188	DDX21	A015-C-203	Human	Colorectum	FAP	1.85e-20	-4.17e-01	-0.1294
9188	DDX21	A002-C-201	Human	Colorectum	FAP	2.06e-07	-2.99e-01	0.0324
9188	DDX21	A002-C-203	Human	Colorectum	FAP	1.46e-02	-2.13e-01	0.2786
9188	DDX21	A001-C-108	Human	Colorectum	FAP	2.35e-06	4.06e-02	-0.0272
9188	DDX21	A002-C-205	Human	Colorectum	FAP	3.55e-10	-2.59e-02	-0.1236
9188	DDX21	A015-C-006	Human	Colorectum	FAP	7.43e-05	4.39e-02	-0.0994
9188	DDX21	A015-C-106	Human	Colorectum	FAP	4.36e-05	8.19e-02	-0.0511
9188	DDX21	A002-C-114	Human	Colorectum	FAP	4.44e-07	-2.16e-01	-0.1561
9188	DDX21	A015-C-104	Human	Colorectum	FAP	2.84e-15	-1.80e-01	-0.1899
9188	DDX21	A001-C-014	Human	Colorectum	FAP	1.23e-06	1.60e-02	0.0135
9188	DDX21	A002-C-016	Human	Colorectum	FAP	3.55e-12	-1.95e-01	0.0521
9188	DDX21	A015-C-002	Human	Colorectum	FAP	3.30e-03	-1.82e-01	-0.0763
9188	DDX21	A001-C-203	Human	Colorectum	FAP	2.75e-05	-3.06e-02	-0.0481
9188	DDX21	A002-C-116	Human	Colorectum	FAP	3.99e-18	-2.30e-01	-0.0452
9188	DDX21	A014-C-008	Human	Colorectum	FAP	9.42e-06	6.15e-02	-0.191
9188	DDX21	A018-E-020	Human	Colorectum	FAP	2.30e-08	-3.30e-01	-0.2034

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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
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
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:000164914	Endometrium	EEC	osteoblast differentiation	53/2168	229/18723	5.32e-07	2.02e-05	53
GO:000150313	Endometrium	EEC	ossification	79/2168	408/18723	2.72e-06	7.67e-05	79
GO:004312216	Endometrium	EEC	regulation of I-kappaB kinase/NF-kappaB signaling	53/2168	249/18723	7.59e-06	1.73e-04	53
GO:004312314	Endometrium	EEC	positive regulation of I-kappaB kinase/NF-kappaB signaling	42/2168	186/18723	1.47e-05	2.87e-04	42
GO:000724915	Endometrium	EEC	I-kappaB kinase/NF-kappaB signaling	57/2168	281/18723	1.60e-05	3.12e-04	57
GO:000636416	Endometrium	EEC	rRNA processing	48/2168	225/18723	1.88e-05	3.50e-04	48
GO:001607216	Endometrium	EEC	rRNA metabolic process	49/2168	236/18723	3.27e-05	5.62e-04	49
GO:000961513	Endometrium	EEC	response to virus	66/2168	367/18723	1.78e-04	2.20e-03	66
GO:000181913	Endometrium	EEC	positive regulation of cytokine production	73/2168	467/18723	4.64e-03	2.97e-02	73
GO:003447012	Endometrium	EEC	ncRNA processing	63/2168	395/18723	5.20e-03	3.26e-02	63
GO:002261327	Esophagus	HGIN	ribonucleoprotein complex biogenesis	158/2587	463/18723	2.61e-29	5.23e-26	158
GO:004225426	Esophagus	HGIN	ribosome biogenesis	101/2587	299/18723	8.74e-19	4.03e-16	101
GO:001607219	Esophagus	HGIN	rRNA metabolic process	72/2587	236/18723	2.26e-11	2.56e-09	72
GO:000636419	Esophagus	HGIN	rRNA processing	69/2587	225/18723	4.53e-11	5.04e-09	69
GO:003447010	Esophagus	HGIN	ncRNA processing	97/2587	395/18723	5.92e-09	3.90e-07	97
GO:004312220	Esophagus	HGIN	regulation of I-kappaB kinase/NF-kappaB signaling	63/2587	249/18723	8.91e-07	3.61e-05	63
GO:00346606	Esophagus	HGIN	ncRNA metabolic process	104/2587	485/18723	2.26e-06	8.23e-05	104
GO:000724918	Esophagus	HGIN	I-kappaB kinase/NF-kappaB signaling	67/2587	281/18723	3.84e-06	1.29e-04	67
GO:004312317	Esophagus	HGIN	positive regulation of I-kappaB kinase/NF-kappaB signaling	49/2587	186/18723	4.22e-06	1.40e-04	49
GO:000164917	Esophagus	HGIN	osteoblast differentiation	50/2587	229/18723	5.88e-04	8.30e-03	50

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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

DDX21

SNV

Missense_Mutation

c.1756N>A

p.Val586Met

p.V586M

Q9NR30

protein_coding

deleterious(0.01)

possibly_damaging(0.646)

TCGA-AO-A03P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

DDX21

SNV

Missense_Mutation

rs780033357

c.2113N>G

p.Leu705Val

p.L705V

Q9NR30

protein_coding

deleterious(0.04)

probably_damaging(0.955)

TCGA-BH-A0HO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

DDX21

SNV

Missense_Mutation

c.526N>C

p.Glu176Gln

p.E176Q

Q9NR30

protein_coding

deleterious(0.02)

benign(0.005)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

DDX21

SNV

Missense_Mutation

rs868785299

c.1784A>G

p.Lys595Arg

p.K595R

Q9NR30

protein_coding

tolerated(0.73)

benign(0.009)

TCGA-BH-A201-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DDX21

SNV

Missense_Mutation

rs766890848

c.1873N>A

p.Asp625Asn

p.D625N

Q9NR30

protein_coding

deleterious(0.02)

possibly_damaging(0.484)

TCGA-C8-A12K-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DDX21

SNV

Missense_Mutation

c.1161G>C

p.Lys387Asn

p.K387N

Q9NR30

protein_coding

deleterious(0.04)

benign(0.248)

TCGA-D8-A1J9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DDX21

SNV

Missense_Mutation

novel

c.1209N>C

p.Lys403Asn

p.K403N

Q9NR30

protein_coding

tolerated(0.08)

benign(0.003)

TCGA-E2-A574-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

DDX21

SNV

Missense_Mutation

c.692N>A

p.Arg231Gln

p.R231Q

Q9NR30

protein_coding

deleterious(0.01)

possibly_damaging(0.826)

TCGA-GM-A2DF-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

DDX21

insertion

Frame_Shift_Ins

novel

c.1897_1898insG

p.Asn633ArgfsTer14

p.N633Rfs*14

Q9NR30

protein_coding

TCGA-A8-A0A4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

DDX21

insertion

Frame_Shift_Ins

novel

c.1898_1899insGACGGAGTTTCTTAAAATGATTGTG

p.Asn633LysfsTer22

p.N633Kfs*22

Q9NR30

protein_coding

TCGA-A8-A0A4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

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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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