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: MIER1

Gene summary for MIER1

Gene summary.

Gene information	Species	Human
	Gene symbol	MIER1
	Gene ID	57708
	Gene name	MIER1 transcriptional regulator
	Gene Alias	ER1
	Cytomap	1p31.3
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q8N108

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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
57708	MIER1	HTA11_3410_2000001011	Human	Colorectum	AD	9.49e-11	-4.90e-01	0.0155
57708	MIER1	HTA11_347_2000001011	Human	Colorectum	AD	3.65e-06	3.93e-01	-0.1954
57708	MIER1	HTA11_10711_2000001011	Human	Colorectum	AD	3.04e-02	-3.46e-01	0.0338
57708	MIER1	HTA11_7696_3000711011	Human	Colorectum	AD	3.83e-02	-3.86e-01	0.0674
57708	MIER1	HTA11_99999973899_84307	Human	Colorectum	MSS	3.16e-02	-5.19e-01	0.2585
57708	MIER1	HTA11_99999974143_84620	Human	Colorectum	MSS	1.33e-10	-4.88e-01	0.3005
57708	MIER1	F007	Human	Colorectum	FAP	7.04e-05	-4.06e-01	0.1176
57708	MIER1	A002-C-010	Human	Colorectum	FAP	3.37e-04	-2.69e-01	0.242
57708	MIER1	A001-C-207	Human	Colorectum	FAP	9.41e-06	-3.27e-01	0.1278
57708	MIER1	A015-C-203	Human	Colorectum	FAP	2.10e-20	-4.11e-01	-0.1294
57708	MIER1	A015-C-204	Human	Colorectum	FAP	4.77e-06	-3.46e-01	-0.0228
57708	MIER1	A014-C-040	Human	Colorectum	FAP	8.57e-04	-2.79e-01	-0.1184
57708	MIER1	A002-C-201	Human	Colorectum	FAP	5.39e-16	-4.56e-01	0.0324
57708	MIER1	A002-C-203	Human	Colorectum	FAP	1.39e-06	-3.83e-01	0.2786
57708	MIER1	A001-C-119	Human	Colorectum	FAP	1.87e-06	-3.34e-01	-0.1557
57708	MIER1	A001-C-108	Human	Colorectum	FAP	1.80e-12	-3.91e-01	-0.0272
57708	MIER1	A002-C-205	Human	Colorectum	FAP	2.66e-21	-4.24e-01	-0.1236
57708	MIER1	A001-C-104	Human	Colorectum	FAP	3.89e-03	-3.23e-01	0.0184
57708	MIER1	A015-C-005	Human	Colorectum	FAP	7.45e-08	-4.26e-01	-0.0336
57708	MIER1	A015-C-006	Human	Colorectum	FAP	8.72e-18	-5.51e-01	-0.0994

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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: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: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:0016570	Colorectum	MSS	histone modification	113/3467	463/18723	8.37e-04	8.68e-03	113
GO:00165701	Colorectum	FAP	histone modification	94/2622	463/18723	1.06e-04	1.76e-03	94
GO:00431222	Colorectum	FAP	regulation of I-kappaB kinase/NF-kappaB signaling	56/2622	249/18723	1.82e-04	2.69e-03	56
GO:00431232	Colorectum	FAP	positive regulation of I-kappaB kinase/NF-kappaB signaling	42/2622	186/18723	1.01e-03	9.89e-03	42
GO:00072492	Colorectum	FAP	I-kappaB kinase/NF-kappaB signaling	58/2622	281/18723	1.37e-03	1.24e-02	58
GO:00165702	Colorectum	CRC	histone modification	75/2078	463/18723	4.95e-04	7.06e-03	75
GO:00431223	Colorectum	CRC	regulation of I-kappaB kinase/NF-kappaB signaling	41/2078	249/18723	6.39e-03	4.64e-02	41
GO:001657015	Esophagus	ESCC	histone modification	323/8552	463/18723	2.61e-26	7.88e-24	323
GO:004312318	Esophagus	ESCC	positive regulation of I-kappaB kinase/NF-kappaB signaling	132/8552	186/18723	2.07e-12	8.58e-11	132
GO:0043122110	Esophagus	ESCC	regulation of I-kappaB kinase/NF-kappaB signaling	167/8552	249/18723	6.11e-12	2.32e-10	167
GO:000724919	Esophagus	ESCC	I-kappaB kinase/NF-kappaB signaling	183/8552	281/18723	3.02e-11	1.01e-09	183
GO:00356015	Esophagus	ESCC	protein deacylation	79/8552	112/18723	8.30e-08	1.42e-06	79
GO:00987325	Esophagus	ESCC	macromolecule deacylation	80/8552	116/18723	3.19e-07	4.50e-06	80
GO:00165754	Esophagus	ESCC	histone deacetylation	60/8552	82/18723	3.85e-07	5.32e-06	60

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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

MIER1

SNV

Missense_Mutation

novel

c.1414N>C

p.Val472Leu

p.V472L

Q8N108

protein_coding

tolerated(0.21)

benign(0.003)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

MIER1

SNV

Missense_Mutation

c.1423N>C

p.Glu475Gln

p.E475Q

Q8N108

protein_coding

deleterious(0.05)

benign(0.03)

TCGA-A8-A06Q-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

MIER1

SNV

Missense_Mutation

c.328N>A

p.Asp110Asn

p.D110N

Q8N108

protein_coding

tolerated(0.09)

benign(0.387)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MIER1

deletion

Frame_Shift_Del

novel

c.1503delN

p.Asp502IlefsTer12

p.D502Ifs*12

Q8N108

protein_coding

TCGA-A7-A425-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

adriamycin

MIER1

insertion

Nonsense_Mutation

novel

c.160_161insAATGCACACAACACAAGGAAGTTACTGGGAATTCTTCTGTCTAGCCT

p.Val54GlufsTer15

p.V54Efs*15

Q8N108

protein_coding

TCGA-AR-A1AL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

anastrozole

MIER1

deletion

Frame_Shift_Del

novel

c.304delA

p.Thr102GlnfsTer7

p.T102Qfs*7

Q8N108

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

MIER1

SNV

Missense_Mutation

c.451N>A

p.Asp151Asn

p.D151N

Q8N108

protein_coding

tolerated(0.47)

benign(0.25)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

MIER1

SNV

Missense_Mutation

c.418G>A

p.Glu140Lys

p.E140K

Q8N108

protein_coding

tolerated(0.39)

benign(0.065)

TCGA-EA-A439-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MIER1

SNV

Missense_Mutation

c.658G>A

p.Glu220Lys

p.E220K

Q8N108

protein_coding

deleterious(0.04)

benign(0.277)

TCGA-EK-A2PG-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

MIER1

SNV

Missense_Mutation

c.138G>C

p.Arg46Ser

p.R46S

Q8N108

protein_coding

deleterious_low_confidence(0.04)

benign(0.027)

TCGA-A6-6781-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

oxaliplatin

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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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