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: ENC1

Gene summary for ENC1

Gene summary.

Gene information	Species	Human
	Gene symbol	ENC1
	Gene ID	8507
	Gene name	ectodermal-neural cortex 1
	Gene Alias	CCL28
	Cytomap	5q13.3
	Gene Type	protein-coding
	GO ID	GO:0006412
	UniProtAcc	O14682

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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
8507	ENC1	HTA11_99999965104_69814	Human	Colorectum	MSS	2.74e-11	7.33e-01	0.281
8507	ENC1	F007	Human	Colorectum	FAP	4.95e-06	6.38e-01	0.1176
8507	ENC1	A002-C-010	Human	Colorectum	FAP	1.67e-03	3.26e-01	0.242
8507	ENC1	A001-C-207	Human	Colorectum	FAP	1.79e-07	6.09e-01	0.1278
8507	ENC1	A015-C-203	Human	Colorectum	FAP	8.36e-35	8.76e-01	-0.1294
8507	ENC1	A015-C-204	Human	Colorectum	FAP	2.51e-12	7.00e-01	-0.0228
8507	ENC1	A014-C-040	Human	Colorectum	FAP	2.34e-04	6.43e-01	-0.1184
8507	ENC1	A002-C-201	Human	Colorectum	FAP	9.78e-16	6.55e-01	0.0324
8507	ENC1	A002-C-203	Human	Colorectum	FAP	9.09e-10	5.88e-01	0.2786
8507	ENC1	A001-C-108	Human	Colorectum	FAP	1.97e-18	6.47e-01	-0.0272
8507	ENC1	A002-C-021	Human	Colorectum	FAP	2.29e-08	4.05e-01	0.1171
8507	ENC1	A002-C-205	Human	Colorectum	FAP	2.58e-14	5.19e-01	-0.1236
8507	ENC1	A001-C-104	Human	Colorectum	FAP	1.92e-14	6.19e-01	0.0184
8507	ENC1	A015-C-005	Human	Colorectum	FAP	4.09e-04	4.67e-01	-0.0336
8507	ENC1	A015-C-006	Human	Colorectum	FAP	3.06e-15	6.83e-01	-0.0994
8507	ENC1	A015-C-106	Human	Colorectum	FAP	2.67e-22	7.69e-01	-0.0511
8507	ENC1	A002-C-114	Human	Colorectum	FAP	1.87e-04	2.00e-01	-0.1561
8507	ENC1	A015-C-104	Human	Colorectum	FAP	5.02e-31	7.96e-01	-0.1899
8507	ENC1	A001-C-014	Human	Colorectum	FAP	1.63e-13	6.56e-01	0.0135
8507	ENC1	A002-C-016	Human	Colorectum	FAP	1.29e-06	3.47e-01	0.0521

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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
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:00104982	Colorectum	MSS	proteasomal protein catabolic process	157/3467	490/18723	2.39e-13	5.25e-11	157
GO:00064172	Colorectum	MSS	regulation of translation	134/3467	468/18723	4.43e-08	2.38e-06	134
GO:00313462	Colorectum	MSS	positive regulation of cell projection organization	96/3467	353/18723	3.44e-05	6.70e-04	96
GO:00109752	Colorectum	MSS	regulation of neuron projection development	115/3467	445/18723	6.91e-05	1.20e-03	115
GO:0017148	Colorectum	MSS	negative regulation of translation	64/3467	245/18723	1.94e-03	1.67e-02	64
GO:0034249	Colorectum	MSS	negative regulation of cellular amide metabolic process	70/3467	273/18723	2.07e-03	1.76e-02	70
GO:00064174	Colorectum	FAP	regulation of translation	111/2622	468/18723	8.47e-09	1.13e-06	111
GO:00109753	Colorectum	FAP	regulation of neuron projection development	102/2622	445/18723	2.04e-07	1.24e-05	102
GO:00104984	Colorectum	FAP	proteasomal protein catabolic process	110/2622	490/18723	2.12e-07	1.26e-05	110
GO:00313463	Colorectum	FAP	positive regulation of cell projection organization	82/2622	353/18723	1.78e-06	7.35e-05	82
GO:00171481	Colorectum	FAP	negative regulation of translation	50/2622	245/18723	3.57e-03	2.57e-02	50
GO:00342491	Colorectum	FAP	negative regulation of cellular amide metabolic process	54/2622	273/18723	5.00e-03	3.33e-02	54
GO:00109754	Colorectum	CRC	regulation of neuron projection development	82/2078	445/18723	2.51e-06	1.19e-04	82
GO:00313464	Colorectum	CRC	positive regulation of cell projection organization	67/2078	353/18723	7.45e-06	2.72e-04	67
GO:00064175	Colorectum	CRC	regulation of translation	82/2078	468/18723	1.79e-05	5.40e-04	82
GO:00104985	Colorectum	CRC	proteasomal protein catabolic process	77/2078	490/18723	1.03e-03	1.21e-02	77
GO:00342492	Colorectum	CRC	negative regulation of cellular amide metabolic process	45/2078	273/18723	4.35e-03	3.47e-02	45
GO:00171482	Colorectum	CRC	negative regulation of translation	41/2078	245/18723	4.82e-03	3.72e-02	41
GO:0010498111	Esophagus	ESCC	proteasomal protein catabolic process	369/8552	490/18723	1.13e-41	1.80e-38	369
GO:0006417111	Esophagus	ESCC	regulation of translation	304/8552	468/18723	1.53e-17	1.33e-15	304

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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

ENC1

SNV

Missense_Mutation

novel

c.1040N>T

p.Gly347Val

p.G347V

O14682

protein_coding

deleterious(0.04)

probably_damaging(0.957)

TCGA-A7-A4SE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ENC1

SNV

Missense_Mutation

c.901G>C

p.Gly301Arg

p.G301R

O14682

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-A8-A09A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ENC1

SNV

Missense_Mutation

c.392N>T

p.Asp131Val

p.D131V

O14682

protein_coding

tolerated(0.25)

possibly_damaging(0.794)

TCGA-AO-A1KT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

fluorouracil

ENC1

insertion

Frame_Shift_Ins

novel

c.686_687insGAGC

p.Pro230SerfsTer35

p.P230Sfs*35

O14682

protein_coding

TCGA-A2-A0CQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ENC1

insertion

In_Frame_Ins

novel

c.685_686insAGTGGACCAAAGTGGGAGATGTGACAGCAAAGCGCA

p.Leu229delinsGlnTrpThrLysValGlyAspValThrAlaLysArgIle

p.L229delinsQWTKVGDVTAKRI

O14682

protein_coding

TCGA-A2-A0CQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ENC1

insertion

In_Frame_Ins

novel

c.229_230insAAT

p.Gly77delinsGluCys

p.G77delinsEC

O14682

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ENC1

insertion

In_Frame_Ins

novel

c.228_229insAAGGCTGGCACTTCTGCCAGCCATCTATCTCATGGA

p.Ser76_Gly77insLysAlaGlyThrSerAlaSerHisLeuSerHisGly

p.S76_G77insKAGTSASHLSHG

O14682

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ENC1

insertion

Frame_Shift_Ins

novel

c.290_291insTGGACTGCTACGATCCAACA

p.Leu98GlyfsTer103

p.L98Gfs*103

O14682

protein_coding

TCGA-BH-A0EB-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ENC1

SNV

Missense_Mutation

c.367N>T

p.Ala123Ser

p.A123S

O14682

protein_coding

deleterious(0.01)

probably_damaging(0.99)

TCGA-JW-A5VK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ENC1

SNV

Missense_Mutation

novel

c.1726N>C

p.Ile576Leu

p.I576L

O14682

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.626)

TCGA-A6-5665-01

Colorectum

colon adenocarcinoma

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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