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: EMC1

Gene summary for EMC1

Gene summary.

Gene information	Species	Human
	Gene symbol	EMC1
	Gene ID	23065
	Gene name	ER membrane protein complex subunit 1
	Gene Alias	CAVIPMR
	Cytomap	1p36.13
	Gene Type	protein-coding
	GO ID	GO:0006996
	UniProtAcc	Q8N766

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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
23065	EMC1	LZE7T	Human	Esophagus	ESCC	1.81e-04	1.97e-01	0.0667
23065	EMC1	LZE8T	Human	Esophagus	ESCC	1.65e-03	6.35e-02	0.067
23065	EMC1	LZE24T	Human	Esophagus	ESCC	2.18e-10	1.29e-01	0.0596
23065	EMC1	P2T-E	Human	Esophagus	ESCC	1.09e-33	4.53e-01	0.1177
23065	EMC1	P4T-E	Human	Esophagus	ESCC	1.43e-05	2.18e-01	0.1323
23065	EMC1	P5T-E	Human	Esophagus	ESCC	3.47e-11	3.30e-02	0.1327
23065	EMC1	P8T-E	Human	Esophagus	ESCC	4.48e-17	1.90e-01	0.0889
23065	EMC1	P9T-E	Human	Esophagus	ESCC	3.31e-09	3.19e-02	0.1131
23065	EMC1	P10T-E	Human	Esophagus	ESCC	9.75e-20	2.82e-01	0.116
23065	EMC1	P11T-E	Human	Esophagus	ESCC	1.63e-20	5.04e-01	0.1426
23065	EMC1	P12T-E	Human	Esophagus	ESCC	2.95e-21	2.41e-01	0.1122
23065	EMC1	P15T-E	Human	Esophagus	ESCC	5.28e-26	6.56e-01	0.1149
23065	EMC1	P16T-E	Human	Esophagus	ESCC	1.02e-26	3.79e-01	0.1153
23065	EMC1	P17T-E	Human	Esophagus	ESCC	1.30e-08	4.18e-01	0.1278
23065	EMC1	P19T-E	Human	Esophagus	ESCC	8.91e-04	3.87e-01	0.1662
23065	EMC1	P20T-E	Human	Esophagus	ESCC	1.24e-10	3.34e-01	0.1124
23065	EMC1	P21T-E	Human	Esophagus	ESCC	4.54e-32	6.72e-01	0.1617
23065	EMC1	P22T-E	Human	Esophagus	ESCC	3.31e-21	1.18e-01	0.1236
23065	EMC1	P23T-E	Human	Esophagus	ESCC	1.46e-12	1.93e-01	0.108
23065	EMC1	P24T-E	Human	Esophagus	ESCC	1.35e-16	2.05e-01	0.1287

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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
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:0090132111	Thyroid	PTC	epithelium migration	149/5968	360/18723	7.89e-05	6.74e-04	149
GO:00450485	Thyroid	PTC	protein insertion into ER membrane	16/5968	22/18723	9.98e-05	8.15e-04	16
GO:0090130111	Thyroid	PTC	tissue migration	150/5968	365/18723	1.13e-04	9.01e-04	150
GO:0010632111	Thyroid	PTC	regulation of epithelial cell migration	123/5968	292/18723	1.33e-04	1.05e-03	123
GO:001059516	Thyroid	PTC	positive regulation of endothelial cell migration	61/5968	133/18723	4.95e-04	3.25e-03	61
GO:0070302110	Thyroid	PTC	regulation of stress-activated protein kinase signaling cascade	83/5968	195/18723	1.04e-03	6.21e-03	83
GO:00718165	Thyroid	PTC	tail-anchored membrane protein insertion into ER membrane	12/5968	17/18723	1.20e-03	6.89e-03	12
GO:0032872110	Thyroid	PTC	regulation of stress-activated MAPK cascade	81/5968	192/18723	1.62e-03	8.95e-03	81
GO:004354219	Thyroid	PTC	endothelial cell migration	112/5968	279/18723	2.03e-03	1.09e-02	112
GO:00450505	Thyroid	PTC	protein insertion into ER membrane by stop-transfer membrane-anchor sequence	8/5968	10/18723	2.46e-03	1.27e-02	8
GO:004576612	Thyroid	PTC	positive regulation of angiogenesis	75/5968	181/18723	4.09e-03	1.95e-02	75
GO:190401812	Thyroid	PTC	positive regulation of vasculature development	75/5968	181/18723	4.09e-03	1.95e-02	75
GO:001059416	Thyroid	PTC	regulation of endothelial cell migration	91/5968	232/18723	1.03e-02	4.18e-02	91
GO:001059522	Thyroid	goiters	positive regulation of endothelial cell migration	15/497	133/18723	2.55e-06	1.27e-04	15
GO:001063426	Thyroid	goiters	positive regulation of epithelial cell migration	17/497	176/18723	4.76e-06	2.22e-04	17
GO:001059422	Thyroid	goiters	regulation of endothelial cell migration	18/497	232/18723	5.06e-05	1.73e-03	18
GO:004354223	Thyroid	goiters	endothelial cell migration	20/497	279/18723	6.02e-05	2.03e-03	20
GO:009015026	Thyroid	goiters	establishment of protein localization to membrane	19/497	260/18723	7.09e-05	2.37e-03	19
GO:001063225	Thyroid	goiters	regulation of epithelial cell migration	20/497	292/18723	1.13e-04	3.45e-03	20
GO:009013027	Thyroid	goiters	tissue migration	23/497	365/18723	1.25e-04	3.77e-03	23

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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

EMC1

SNV

Missense_Mutation

novel

c.1799C>A

p.Ser600Tyr

p.S600Y

Q8N766

protein_coding

tolerated(1)

benign(0.086)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EMC1

SNV

Missense_Mutation

novel

c.1283A>G

p.His428Arg

p.H428R

Q8N766

protein_coding

tolerated(0.11)

benign(0.003)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EMC1

SNV

Missense_Mutation

novel

c.64G>A

p.Val22Ile

p.V22I

Q8N766

protein_coding

tolerated(0.1)

benign(0.228)

TCGA-B6-A2IU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

EMC1

SNV

Missense_Mutation

c.1525N>A

p.Ala509Thr

p.A509T

Q8N766

protein_coding

tolerated(0.08)

benign(0.015)

TCGA-BH-A18H-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

EMC1

SNV

Missense_Mutation

c.2567N>A

p.Ile856Asn

p.I856N

Q8N766

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-E9-A1RI-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

tamoxiphen

EMC1

insertion

Nonsense_Mutation

novel

c.1119_1120insTGACTTGTTAGAAGTCACAGTAAAGGCGGGTATTATTT

p.Thr374Ter

p.T374*

Q8N766

protein_coding

TCGA-A2-A04Y-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

EMC1

insertion

Frame_Shift_Ins

novel

c.1321_1322insATTGTTTTGAAGA

p.Val441AspfsTer10

p.V441Dfs*10

Q8N766

protein_coding

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EMC1

insertion

Nonsense_Mutation

novel

c.1319_1320insATAATGGGGATAATAGCACCAACGTCAGA

p.Val441Ter

p.V441*

Q8N766

protein_coding

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EMC1

insertion

In_Frame_Ins

novel

c.185_186insTCACTCTGTCACCCAGGCTAGAGTGCAGTG

p.Val62_Ile63insHisSerValThrGlnAlaArgValGlnTrp

p.V62_I63insHSVTQARVQW

Q8N766

protein_coding

TCGA-A8-A0A2-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

EMC1

insertion

Frame_Shift_Ins

novel

c.2326_2327insCAACCACCATCTTGTCGGGTTTTCTTACCTCCAT

p.Lys776ThrfsTer48

p.K776Tfs*48

Q8N766

protein_coding

TCGA-AO-A03R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

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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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