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: ERGIC2

Gene summary for ERGIC2

Gene summary.

Gene information	Species	Human
	Gene symbol	ERGIC2
	Gene ID	51290
	Gene name	ERGIC and golgi 2
	Gene Alias	CDA14
	Cytomap	12p11.22
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	A0A024RB08

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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
51290	ERGIC2	LZE2T	Human	Esophagus	ESCC	2.46e-02	3.49e-01	0.082
51290	ERGIC2	LZE4T	Human	Esophagus	ESCC	2.27e-19	5.15e-01	0.0811
51290	ERGIC2	LZE7T	Human	Esophagus	ESCC	2.36e-07	5.96e-01	0.0667
51290	ERGIC2	LZE8T	Human	Esophagus	ESCC	5.81e-22	9.95e-01	0.067
51290	ERGIC2	LZE20T	Human	Esophagus	ESCC	3.10e-16	4.68e-01	0.0662
51290	ERGIC2	LZE22D1	Human	Esophagus	HGIN	9.57e-05	1.08e-01	0.0595
51290	ERGIC2	LZE22T	Human	Esophagus	ESCC	2.05e-04	3.00e-01	0.068
51290	ERGIC2	LZE24T	Human	Esophagus	ESCC	1.83e-31	7.36e-01	0.0596
51290	ERGIC2	LZE22D3	Human	Esophagus	HGIN	4.41e-02	2.75e-01	0.0653
51290	ERGIC2	LZE21T	Human	Esophagus	ESCC	9.44e-03	3.62e-01	0.0655
51290	ERGIC2	LZE6T	Human	Esophagus	ESCC	1.76e-08	2.58e-01	0.0845
51290	ERGIC2	P1T-E	Human	Esophagus	ESCC	3.31e-09	5.31e-01	0.0875
51290	ERGIC2	P2T-E	Human	Esophagus	ESCC	1.12e-64	1.12e+00	0.1177
51290	ERGIC2	P4T-E	Human	Esophagus	ESCC	2.82e-46	1.04e+00	0.1323
51290	ERGIC2	P5T-E	Human	Esophagus	ESCC	7.19e-28	6.65e-01	0.1327
51290	ERGIC2	P8T-E	Human	Esophagus	ESCC	8.73e-49	1.00e+00	0.0889
51290	ERGIC2	P9T-E	Human	Esophagus	ESCC	5.70e-17	3.81e-01	0.1131
51290	ERGIC2	P10T-E	Human	Esophagus	ESCC	2.94e-48	9.17e-01	0.116
51290	ERGIC2	P11T-E	Human	Esophagus	ESCC	3.08e-19	6.70e-01	0.1426
51290	ERGIC2	P12T-E	Human	Esophagus	ESCC	1.17e-62	1.21e+00	0.1122

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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
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:004819317	Esophagus	HGIN	Golgi vesicle transport	83/2587	296/18723	8.59e-11	8.89e-09	83
GO:00068889	Esophagus	HGIN	endoplasmic reticulum to Golgi vesicle-mediated transport	40/2587	130/18723	4.67e-07	2.07e-05	40
GO:000689016	Esophagus	HGIN	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	19/2587	52/18723	3.44e-05	8.67e-04	19
GO:004819318	Esophagus	ESCC	Golgi vesicle transport	231/8552	296/18723	1.82e-30	9.63e-28	231
GO:000688815	Esophagus	ESCC	endoplasmic reticulum to Golgi vesicle-mediated transport	102/8552	130/18723	1.73e-14	9.22e-13	102
GO:000689017	Esophagus	ESCC	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	46/8552	52/18723	1.23e-10	3.66e-09	46
GO:004819311	Liver	Cirrhotic	Golgi vesicle transport	153/4634	296/18723	1.02e-23	6.43e-21	153
GO:000688811	Liver	Cirrhotic	endoplasmic reticulum to Golgi vesicle-mediated transport	77/4634	130/18723	5.78e-17	7.56e-15	77
GO:00068905	Liver	Cirrhotic	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	29/4634	52/18723	1.69e-06	3.22e-05	29
GO:004819321	Liver	HCC	Golgi vesicle transport	217/7958	296/18723	2.58e-27	1.02e-24	217
GO:000688821	Liver	HCC	endoplasmic reticulum to Golgi vesicle-mediated transport	100/7958	130/18723	1.15e-15	8.67e-14	100
GO:000689011	Liver	HCC	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	36/7958	52/18723	8.79e-05	7.66e-04	36
GO:004819315	Oral cavity	OSCC	Golgi vesicle transport	209/7305	296/18723	1.39e-28	6.30e-26	209
GO:00068888	Oral cavity	OSCC	endoplasmic reticulum to Golgi vesicle-mediated transport	97/7305	130/18723	1.42e-16	1.15e-14	97
GO:000689010	Oral cavity	OSCC	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	40/7305	52/18723	2.86e-08	5.50e-07	40
GO:004819316	Oral cavity	LP	Golgi vesicle transport	141/4623	296/18723	6.11e-18	1.06e-15	141
GO:000688814	Oral cavity	LP	endoplasmic reticulum to Golgi vesicle-mediated transport	67/4623	130/18723	3.74e-11	2.39e-09	67
GO:000689015	Oral cavity	LP	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	29/4623	52/18723	1.60e-06	3.79e-05	29
GO:004819310	Prostate	BPH	Golgi vesicle transport	102/3107	296/18723	3.90e-14	4.56e-12	102
GO:00068887	Prostate	BPH	endoplasmic reticulum to Golgi vesicle-mediated transport	46/3107	130/18723	1.53e-07	3.53e-06	46

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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

ERGIC2

SNV

Missense_Mutation

novel

c.556C>T

p.His186Tyr

p.H186Y

Q96RQ1

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-VS-A94X-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ERGIC2

SNV

Missense_Mutation

novel

c.739N>C

p.Phe247Leu

p.F247L

Q96RQ1

protein_coding

deleterious(0.01)

possibly_damaging(0.489)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

ERGIC2

SNV

Missense_Mutation

novel

c.677T>C

p.Val226Ala

p.V226A

Q96RQ1

protein_coding

tolerated(0.4)

benign(0.009)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

ERGIC2

SNV

Missense_Mutation

novel

c.61N>C

p.Lys21Gln

p.K21Q

Q96RQ1

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AJ-A3BH-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

ERGIC2

SNV

Missense_Mutation

c.517C>A

p.His173Asn

p.H173N

Q96RQ1

protein_coding

deleterious(0)

probably_damaging(0.948)

TCGA-AP-A056-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

ERGIC2

SNV

Missense_Mutation

c.337G>A

p.Val113Ile

p.V113I

Q96RQ1

protein_coding

tolerated(0.41)

benign(0)

TCGA-AP-A056-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

ERGIC2

SNV

Missense_Mutation

c.224G>T

p.Arg75Ile

p.R75I

Q96RQ1

protein_coding

deleterious(0)

benign(0.206)

TCGA-AP-A056-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

ERGIC2

SNV

Missense_Mutation

novel

c.670G>A

p.Glu224Lys

p.E224K

Q96RQ1

protein_coding

tolerated(0.26)

benign(0.056)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

ERGIC2

SNV

Missense_Mutation

rs761483514

c.590N>A

p.Arg197His

p.R197H

Q96RQ1

protein_coding

deleterious(0.04)

possibly_damaging(0.88)

TCGA-AX-A05Z-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

ERGIC2

SNV

Missense_Mutation

rs375624509

c.17N>A

p.Arg6Gln

p.R6Q

Q96RQ1

protein_coding

tolerated(0.07)

benign(0.181)

TCGA-AX-A1CE-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

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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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