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: ERGIC1

Gene summary for ERGIC1

Gene summary.

Gene information	Species	Human
	Gene symbol	ERGIC1
	Gene ID	57222
	Gene name	endoplasmic reticulum-golgi intermediate compartment 1
	Gene Alias	AMC2
	Cytomap	5q35.1
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	Q969X5

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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
57222	ERGIC1	P84T-E	Human	Esophagus	ESCC	1.87e-04	1.87e-01	0.0933
57222	ERGIC1	P89T-E	Human	Esophagus	ESCC	2.22e-20	1.28e+00	0.1752
57222	ERGIC1	P91T-E	Human	Esophagus	ESCC	1.51e-05	8.22e-01	0.1828
57222	ERGIC1	P94T-E	Human	Esophagus	ESCC	5.20e-03	9.27e-01	0.0879
57222	ERGIC1	P104T-E	Human	Esophagus	ESCC	5.56e-04	5.70e-01	0.0931
57222	ERGIC1	P107T-E	Human	Esophagus	ESCC	5.05e-32	8.50e-01	0.171
57222	ERGIC1	P126T-E	Human	Esophagus	ESCC	4.11e-08	9.83e-01	0.1125
57222	ERGIC1	P127T-E	Human	Esophagus	ESCC	1.88e-06	1.03e-01	0.0826
57222	ERGIC1	P128T-E	Human	Esophagus	ESCC	7.11e-23	8.53e-01	0.1241
57222	ERGIC1	P130T-E	Human	Esophagus	ESCC	2.63e-25	6.68e-01	0.1676
57222	ERGIC1	NAFLD1	Human	Liver	NAFLD	2.90e-10	8.58e-01	-0.04
57222	ERGIC1	S43	Human	Liver	Cirrhotic	7.08e-09	9.60e-02	-0.0187
57222	ERGIC1	HCC1_Meng	Human	Liver	HCC	1.59e-74	1.14e-01	0.0246
57222	ERGIC1	HCC2_Meng	Human	Liver	HCC	4.52e-29	7.31e-02	0.0107
57222	ERGIC1	cirrhotic3	Human	Liver	Cirrhotic	3.87e-02	3.71e-02	0.0215
57222	ERGIC1	HCC2	Human	Liver	HCC	1.38e-19	2.97e+00	0.5341
57222	ERGIC1	HCC5	Human	Liver	HCC	4.12e-02	-9.26e-02	0.4932
57222	ERGIC1	Pt13.b	Human	Liver	HCC	3.54e-08	7.95e-02	0.0251
57222	ERGIC1	Pt14.a	Human	Liver	HCC	1.92e-03	3.32e-01	0.0169
57222	ERGIC1	Pt14.b	Human	Liver	HCC	4.86e-02	9.96e-02	0.018

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
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:00068906	Breast	IDC	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	10/1434	52/18723	5.49e-03	4.03e-02	10
GO:000689012	Breast	DCIS	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	10/1390	52/18723	4.41e-03	3.41e-02	10
GO:0048193	Colorectum	AD	Golgi vesicle transport	109/3918	296/18723	1.80e-10	1.68e-08	109
GO:0006890	Colorectum	AD	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	27/3918	52/18723	7.67e-07	2.70e-05	27
GO:0006888	Colorectum	AD	endoplasmic reticulum to Golgi vesicle-mediated transport	44/3918	130/18723	4.13e-04	4.68e-03	44
GO:00481931	Colorectum	SER	Golgi vesicle transport	79/2897	296/18723	4.20e-07	2.15e-05	79
GO:00068901	Colorectum	SER	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	20/2897	52/18723	4.80e-05	1.18e-03	20
GO:00068881	Colorectum	SER	endoplasmic reticulum to Golgi vesicle-mediated transport	34/2897	130/18723	1.13e-03	1.29e-02	34
GO:00481932	Colorectum	MSS	Golgi vesicle transport	101/3467	296/18723	9.09e-11	9.77e-09	101
GO:00068902	Colorectum	MSS	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	26/3467	52/18723	2.66e-07	1.10e-05	26
GO:00068882	Colorectum	MSS	endoplasmic reticulum to Golgi vesicle-mediated transport	44/3467	130/18723	2.17e-05	4.60e-04	44
GO:00068903	Colorectum	MSI-H	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	13/1319	52/18723	4.72e-05	1.69e-03	13
GO:00068883	Colorectum	MSI-H	endoplasmic reticulum to Golgi vesicle-mediated transport	22/1319	130/18723	1.05e-04	3.24e-03	22
GO:00481933	Colorectum	MSI-H	Golgi vesicle transport	39/1319	296/18723	1.17e-04	3.51e-03	39
GO:00481934	Colorectum	FAP	Golgi vesicle transport	77/2622	296/18723	2.86e-08	2.62e-06	77
GO:00068904	Colorectum	FAP	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	18/2622	52/18723	1.48e-04	2.29e-03	18
GO:00068884	Colorectum	FAP	endoplasmic reticulum to Golgi vesicle-mediated transport	30/2622	130/18723	3.51e-03	2.53e-02	30
GO:00481935	Colorectum	CRC	Golgi vesicle transport	59/2078	296/18723	5.47e-06	2.17e-04	59
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

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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

ERGIC1

SNV

Missense_Mutation

novel

c.854A>T

p.Gln285Leu

p.Q285L

Q969X5

protein_coding

deleterious(0.03)

benign(0.138)

TCGA-BH-A0B1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

adriamycin

ERGIC1

SNV

Missense_Mutation

novel

c.605N>T

p.Lys202Met

p.K202M

Q969X5

protein_coding

deleterious(0.03)

possibly_damaging(0.575)

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

ERGIC1

insertion

Frame_Shift_Ins

novel

c.649_650insAGGGAGGGAGGGGC

p.Val217GlufsTer125

p.V217Efs*125

Q969X5

protein_coding

TCGA-A2-A0EU-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ERGIC1

insertion

Frame_Shift_Ins

novel

c.855_856insGGGCTGCTAATGTCCTCTGGGGCCACACAACTGTTTATTTCTT

p.Leu286GlyfsTer26

p.L286Gfs*26

Q969X5

protein_coding

TCGA-BH-A0B1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

adriamycin

ERGIC1

insertion

Frame_Shift_Ins

novel

c.604_605insCT

p.Lys202ThrfsTer136

p.K202Tfs*136

Q969X5

protein_coding

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

ERGIC1

insertion

Frame_Shift_Ins

novel

c.839_840insTCTGTCCTTTGTAGCACTTGCCTTGG

p.Trp281LeufsTer65

p.W281Lfs*65

Q969X5

protein_coding

TCGA-BH-A0HB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

ERGIC1

SNV

Missense_Mutation

c.577N>T

p.Pro193Ser

p.P193S

Q969X5

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ERGIC1

SNV

Missense_Mutation

novel

c.320N>C

p.Ile107Thr

p.I107T

Q969X5

protein_coding

tolerated(0.42)

benign(0.005)

TCGA-EI-6507-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

ERGIC1

SNV

Missense_Mutation

novel

c.433N>T

p.Asp145Tyr

p.D145Y

Q969X5

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

ERGIC1

SNV

Missense_Mutation

rs376307473

c.695N>A

p.Arg232His

p.R232H

Q969X5

protein_coding

deleterious(0.05)

probably_damaging(0.988)

TCGA-AJ-A3NE-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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