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: NDFIP2

Gene summary for NDFIP2

Gene summary.

Gene information	Species	Human
	Gene symbol	NDFIP2
	Gene ID	54602
	Gene name	Nedd4 family interacting protein 2
	Gene Alias	N4WBP5A
	Cytomap	13q31.1
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	B4DGY6

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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
54602	NDFIP2	LZE24T	Human	Esophagus	ESCC	1.16e-06	3.66e-01	0.0596
54602	NDFIP2	P2T-E	Human	Esophagus	ESCC	8.01e-14	-8.58e-02	0.1177
54602	NDFIP2	P4T-E	Human	Esophagus	ESCC	3.39e-17	7.58e-02	0.1323
54602	NDFIP2	P5T-E	Human	Esophagus	ESCC	3.08e-16	1.53e-02	0.1327
54602	NDFIP2	P8T-E	Human	Esophagus	ESCC	6.25e-19	6.35e-01	0.0889
54602	NDFIP2	P9T-E	Human	Esophagus	ESCC	2.96e-14	1.69e-02	0.1131
54602	NDFIP2	P10T-E	Human	Esophagus	ESCC	1.83e-13	3.61e-01	0.116
54602	NDFIP2	P11T-E	Human	Esophagus	ESCC	2.22e-07	1.12e+00	0.1426
54602	NDFIP2	P12T-E	Human	Esophagus	ESCC	5.12e-05	7.90e-02	0.1122
54602	NDFIP2	P15T-E	Human	Esophagus	ESCC	1.23e-08	5.62e-02	0.1149
54602	NDFIP2	P16T-E	Human	Esophagus	ESCC	1.24e-23	-8.16e-02	0.1153
54602	NDFIP2	P20T-E	Human	Esophagus	ESCC	1.32e-08	4.60e-02	0.1124
54602	NDFIP2	P21T-E	Human	Esophagus	ESCC	1.07e-19	6.35e-01	0.1617
54602	NDFIP2	P22T-E	Human	Esophagus	ESCC	1.58e-20	-2.76e-01	0.1236
54602	NDFIP2	P23T-E	Human	Esophagus	ESCC	1.32e-03	4.31e-01	0.108
54602	NDFIP2	P24T-E	Human	Esophagus	ESCC	6.73e-12	-2.71e-02	0.1287
54602	NDFIP2	P26T-E	Human	Esophagus	ESCC	1.36e-27	5.80e-01	0.1276
54602	NDFIP2	P27T-E	Human	Esophagus	ESCC	2.09e-15	7.17e-03	0.1055
54602	NDFIP2	P28T-E	Human	Esophagus	ESCC	1.99e-05	-1.29e-01	0.1149
54602	NDFIP2	P30T-E	Human	Esophagus	ESCC	9.11e-13	9.25e-01	0.137

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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
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

∗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:1903320	Colorectum	AD	regulation of protein modification by small protein conjugation or removal	86/3918	242/18723	9.43e-08	4.65e-06	86
GO:0007034	Colorectum	AD	vacuolar transport	60/3918	157/18723	4.97e-07	1.85e-05	60
GO:0031396	Colorectum	AD	regulation of protein ubiquitination	72/3918	210/18723	4.50e-06	1.21e-04	72
GO:0043123	Colorectum	AD	positive regulation of I-kappaB kinase/NF-kappaB signaling	60/3918	186/18723	1.91e-04	2.56e-03	60
GO:0043122	Colorectum	AD	regulation of I-kappaB kinase/NF-kappaB signaling	76/3918	249/18723	2.17e-04	2.85e-03	76
GO:0007249	Colorectum	AD	I-kappaB kinase/NF-kappaB signaling	82/3918	281/18723	6.09e-04	6.40e-03	82
GO:19033202	Colorectum	MSS	regulation of protein modification by small protein conjugation or removal	82/3467	242/18723	7.49e-09	4.63e-07	82
GO:00313962	Colorectum	MSS	regulation of protein ubiquitination	70/3467	210/18723	1.88e-07	8.26e-06	70
GO:00070342	Colorectum	MSS	vacuolar transport	52/3467	157/18723	8.25e-06	2.07e-04	52
GO:00431221	Colorectum	MSS	regulation of I-kappaB kinase/NF-kappaB signaling	71/3467	249/18723	7.12e-05	1.21e-03	71
GO:00072491	Colorectum	MSS	I-kappaB kinase/NF-kappaB signaling	77/3467	281/18723	1.51e-04	2.19e-03	77
GO:00431231	Colorectum	MSS	positive regulation of I-kappaB kinase/NF-kappaB signaling	55/3467	186/18723	1.60e-04	2.29e-03	55
GO:00324091	Colorectum	MSS	regulation of transporter activity	78/3467	310/18723	2.09e-03	1.78e-02	78
GO:00510511	Colorectum	MSS	negative regulation of transport	110/3467	470/18723	4.20e-03	3.04e-02	110
GO:19033204	Colorectum	FAP	regulation of protein modification by small protein conjugation or removal	61/2622	242/18723	2.36e-06	9.21e-05	61
GO:00313964	Colorectum	FAP	regulation of protein ubiquitination	50/2622	210/18723	9.03e-05	1.59e-03	50
GO:00070343	Colorectum	FAP	vacuolar transport	40/2622	157/18723	9.41e-05	1.61e-03	40
GO:00324092	Colorectum	FAP	regulation of transporter activity	67/2622	310/18723	1.59e-04	2.43e-03	67
GO:00431222	Colorectum	FAP	regulation of I-kappaB kinase/NF-kappaB signaling	56/2622	249/18723	1.82e-04	2.69e-03	56
GO:00510512	Colorectum	FAP	negative regulation of transport	91/2622	470/18723	7.09e-04	7.64e-03	91

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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

NDFIP2

SNV

Missense_Mutation

c.203N>T

p.Thr68Met

p.T68M

Q9NV92

protein_coding

deleterious_low_confidence(0)

benign(0.01)

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

NDFIP2

SNV

Missense_Mutation

c.943N>G

p.Leu315Val

p.L315V

Q9NV92

protein_coding

tolerated(0.12)

probably_damaging(0.999)

TCGA-AR-A0TX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NDFIP2

SNV

Missense_Mutation

rs754913477

c.341N>T

p.Asn114Ile

p.N114I

Q9NV92

protein_coding

deleterious(0.01)

benign(0.11)

TCGA-PL-A8LZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

NDFIP2

insertion

Frame_Shift_Ins

novel

c.765_766insTTGCTCTGTTGCCC

p.Asn256LeufsTer8

p.N256Lfs*8

Q9NV92

protein_coding

TCGA-B6-A0IA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NDFIP2

SNV

Missense_Mutation

novel

c.872N>A

p.Gly291Glu

p.G291E

Q9NV92

protein_coding

deleterious(0.03)

probably_damaging(1)

TCGA-VS-A94W-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NDFIP2

deletion

In_Frame_Del

novel

c.826_828delNNN

p.Ile276del

p.I276del

Q9NV92

protein_coding

TCGA-BI-A20A-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NDFIP2

SNV

Missense_Mutation

rs775126701

c.517N>A

p.Val173Met

p.V173M

Q9NV92

protein_coding

deleterious(0.01)

probably_damaging(0.961)

TCGA-AZ-4313-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

NDFIP2

SNV

Missense_Mutation

c.353N>T

p.Ser118Leu

p.S118L

Q9NV92

protein_coding

deleterious(0.03)

benign(0)

TCGA-AH-6544-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

oxaliplatin

NDFIP2

insertion

In_Frame_Ins

novel

c.829_830insTTATTGTCAGGGTGAGTGTCT

p.Arg280_Phe281insValSerValPheIleValArg

p.R280_F281insVSVFIVR

Q9NV92

protein_coding

TCGA-F4-6809-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

NDFIP2

SNV

Missense_Mutation

novel

c.932T>G

p.Phe311Cys

p.F311C

Q9NV92

protein_coding

deleterious(0.03)

probably_damaging(1)

TCGA-AP-A056-01

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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