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: MIEN1

Gene summary for MIEN1

Gene summary.

Gene information	Species	Human
	Gene symbol	MIEN1
	Gene ID	84299
	Gene name	migration and invasion enhancer 1
	Gene Alias	C17orf37
	Cytomap	17q12
	Gene Type	protein-coding
	GO ID	GO:0006915
	UniProtAcc	J3KTI2

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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
84299	MIEN1	GSM4909285	Human	Breast	IDC	1.60e-03	-2.16e-01	0.21
84299	MIEN1	GSM4909288	Human	Breast	IDC	6.47e-05	-4.30e-01	0.0988
84299	MIEN1	GSM4909289	Human	Breast	IDC	8.97e-29	9.46e-01	0.1064
84299	MIEN1	GSM4909290	Human	Breast	IDC	1.48e-97	1.21e+00	0.2096
84299	MIEN1	GSM4909291	Human	Breast	IDC	9.07e-76	1.14e+00	0.1753
84299	MIEN1	GSM4909292	Human	Breast	IDC	2.11e-21	9.57e-01	0.1236
84299	MIEN1	GSM4909293	Human	Breast	IDC	4.48e-167	1.35e+00	0.1581
84299	MIEN1	GSM4909294	Human	Breast	IDC	2.29e-123	1.25e+00	0.2022
84299	MIEN1	GSM4909296	Human	Breast	IDC	6.77e-15	-2.25e-01	0.1524
84299	MIEN1	GSM4909297	Human	Breast	IDC	5.95e-16	-5.51e-02	0.1517
84299	MIEN1	GSM4909301	Human	Breast	IDC	4.14e-08	2.92e-01	0.1577
84299	MIEN1	GSM4909307	Human	Breast	IDC	5.05e-08	3.81e-01	0.1569
84299	MIEN1	GSM4909308	Human	Breast	IDC	5.95e-17	4.99e-01	0.158
84299	MIEN1	GSM4909309	Human	Breast	IDC	1.55e-04	6.36e-02	0.0483
84299	MIEN1	GSM4909311	Human	Breast	IDC	3.98e-33	-3.43e-01	0.1534
84299	MIEN1	GSM4909312	Human	Breast	IDC	3.10e-14	-2.29e-01	0.1552
84299	MIEN1	GSM4909315	Human	Breast	IDC	9.14e-05	-2.84e-01	0.21
84299	MIEN1	GSM4909316	Human	Breast	IDC	1.47e-03	-2.45e-01	0.21
84299	MIEN1	GSM4909318	Human	Breast	IDC	4.08e-02	2.56e-01	0.2031
84299	MIEN1	GSM4909319	Human	Breast	IDC	5.45e-50	-1.25e-01	0.1563

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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
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:00102691	Breast	IDC	response to selenium ion	6/1434	11/18723	6.59e-05	1.35e-03	6
GO:00102692	Breast	DCIS	response to selenium ion	6/1390	11/18723	5.53e-05	1.12e-03	6
GO:0031346	Colorectum	AD	positive regulation of cell projection organization	104/3918	353/18723	8.26e-05	1.30e-03	104
GO:0120034	Colorectum	AD	positive regulation of plasma membrane bounded cell projection assembly	33/3918	105/18723	7.49e-03	4.55e-02	33
GO:0120032	Colorectum	AD	regulation of plasma membrane bounded cell projection assembly	53/3918	186/18723	8.51e-03	4.97e-02	53
GO:00313461	Colorectum	SER	positive regulation of cell projection organization	75/2897	353/18723	2.22e-03	2.14e-02	75
GO:01200321	Colorectum	SER	regulation of plasma membrane bounded cell projection assembly	43/2897	186/18723	3.82e-03	3.16e-02	43
GO:0060491	Colorectum	SER	regulation of cell projection assembly	43/2897	188/18723	4.68e-03	3.70e-02	43
GO:00313462	Colorectum	MSS	positive regulation of cell projection organization	96/3467	353/18723	3.44e-05	6.70e-04	96
GO:01200322	Colorectum	MSS	regulation of plasma membrane bounded cell projection assembly	51/3467	186/18723	1.78e-03	1.58e-02	51
GO:00604911	Colorectum	MSS	regulation of cell projection assembly	51/3467	188/18723	2.28e-03	1.87e-02	51
GO:01200341	Colorectum	MSS	positive regulation of plasma membrane bounded cell projection assembly	30/3467	105/18723	7.74e-03	4.84e-02	30
GO:003134616	Esophagus	ESCC	positive regulation of cell projection organization	201/8552	353/18723	1.19e-05	1.11e-04	201
GO:006049118	Esophagus	ESCC	regulation of cell projection assembly	110/8552	188/18723	2.60e-04	1.58e-03	110
GO:012003218	Esophagus	ESCC	regulation of plasma membrane bounded cell projection assembly	108/8552	186/18723	4.37e-04	2.46e-03	108
GO:01200347	Esophagus	ESCC	positive regulation of plasma membrane bounded cell projection assembly	64/8552	105/18723	1.15e-03	5.70e-03	64
GO:01200326	Liver	Cirrhotic	regulation of plasma membrane bounded cell projection assembly	63/4634	186/18723	3.16e-03	1.78e-02	63
GO:00604915	Liver	Cirrhotic	regulation of cell projection assembly	63/4634	188/18723	4.17e-03	2.22e-02	63
GO:003134611	Liver	HCC	positive regulation of cell projection organization	193/7958	353/18723	2.28e-06	3.08e-05	193
GO:006049112	Liver	HCC	regulation of cell projection assembly	101/7958	188/18723	1.20e-03	6.69e-03	101

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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

MIEN1

SNV

Missense_Mutation

novel

c.328N>G

p.His110Asp

p.H110D

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.711)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MIEN1

deletion

Frame_Shift_Del

rs757438769

c.267_270delGAGT

p.Ser90PhefsTer24

p.S90Ffs*24

protein_coding

TCGA-A2-A0T1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Targeted Molecular therapy

herceptin

MIEN1

deletion

Frame_Shift_Del

rs757438769

c.267_270delNNNN

p.Ser90PhefsTer24

p.S90Ffs*24

protein_coding

TCGA-A2-A0YD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

MIEN1

deletion

Frame_Shift_Del

rs757438769

c.267_270delNNNN

p.Ser90PhefsTer24

p.S90Ffs*24

protein_coding

TCGA-EW-A1PC-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

MIEN1

SNV

Missense_Mutation

c.125T>C

p.Leu42Pro

p.L42P

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

MIEN1

SNV

Missense_Mutation

rs370459758

c.335N>T

p.Thr112Ile

p.T112I

protein_coding

tolerated_low_confidence(0.09)

benign(0.003)

TCGA-AY-6197-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

MIEN1

SNV

Missense_Mutation

c.106N>A

p.Glu36Lys

p.E36K

protein_coding

tolerated(0.24)

benign(0.163)

TCGA-AZ-6599-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

MIEN1

deletion

Frame_Shift_Del

rs757438769

c.267_270delNNNN

p.Ser90PhefsTer24

p.S90Ffs*24

protein_coding

TCGA-AD-6964-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

folfox

MIEN1

SNV

Missense_Mutation

rs190390525

c.317N>T

p.Ala106Val

p.A106V

protein_coding

tolerated_low_confidence(1)

benign(0.005)

TCGA-DI-A1BU-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

paclitaxel

MIEN1

deletion

In_Frame_Del

novel

c.152_154delCGG

p.Pro51_Gly52delinsArg

p.P51_G52delinsR

protein_coding

TCGA-B5-A0K0-01

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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