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: MGA

Gene summary for MGA

Gene summary.

Gene information	Species	Human
	Gene symbol	MGA
	Gene ID	23269
	Gene name	MAX dimerization protein MGA
	Gene Alias	MAD5
	Cytomap	15q15.1
	Gene Type	protein-coding
	GO ID	GO:0001708
	UniProtAcc	B9EGR5

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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
23269	MGA	CCI_2	Human	Cervix	CC	6.89e-19	1.56e+00	0.5249
23269	MGA	CCI_3	Human	Cervix	CC	9.22e-05	6.23e-01	0.516
23269	MGA	LZE4T	Human	Esophagus	ESCC	2.75e-09	2.77e-01	0.0811
23269	MGA	LZE7T	Human	Esophagus	ESCC	1.98e-10	6.15e-01	0.0667
23269	MGA	LZE8T	Human	Esophagus	ESCC	3.34e-02	6.30e-02	0.067
23269	MGA	LZE24T	Human	Esophagus	ESCC	1.35e-13	2.65e-01	0.0596
23269	MGA	LZE6T	Human	Esophagus	ESCC	4.02e-04	1.30e-01	0.0845
23269	MGA	P1T-E	Human	Esophagus	ESCC	9.75e-07	3.57e-01	0.0875
23269	MGA	P2T-E	Human	Esophagus	ESCC	1.63e-21	2.74e-01	0.1177
23269	MGA	P4T-E	Human	Esophagus	ESCC	4.87e-05	1.58e-01	0.1323
23269	MGA	P5T-E	Human	Esophagus	ESCC	2.19e-12	1.42e-01	0.1327
23269	MGA	P8T-E	Human	Esophagus	ESCC	1.83e-26	4.24e-01	0.0889
23269	MGA	P9T-E	Human	Esophagus	ESCC	2.53e-08	2.07e-01	0.1131
23269	MGA	P10T-E	Human	Esophagus	ESCC	1.71e-31	5.82e-01	0.116
23269	MGA	P11T-E	Human	Esophagus	ESCC	5.49e-07	2.50e-01	0.1426
23269	MGA	P12T-E	Human	Esophagus	ESCC	3.21e-20	3.60e-01	0.1122
23269	MGA	P15T-E	Human	Esophagus	ESCC	2.19e-19	4.18e-01	0.1149
23269	MGA	P16T-E	Human	Esophagus	ESCC	7.43e-17	2.57e-01	0.1153
23269	MGA	P19T-E	Human	Esophagus	ESCC	6.57e-03	1.92e-01	0.1662
23269	MGA	P20T-E	Human	Esophagus	ESCC	1.11e-09	1.13e-01	0.1124

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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:001905820	Oral cavity	OSCC	viral life cycle	208/7305	317/18723	4.59e-22	1.00e-19	208
GO:00447728	Oral cavity	OSCC	mitotic cell cycle phase transition	255/7305	424/18723	5.29e-19	6.98e-17	255
GO:003465517	Oral cavity	OSCC	nucleobase-containing compound catabolic process	244/7305	407/18723	5.38e-18	5.49e-16	244
GO:00165707	Oral cavity	OSCC	histone modification	270/7305	463/18723	1.59e-17	1.50e-15	270
GO:00073469	Oral cavity	OSCC	regulation of mitotic cell cycle	266/7305	457/18723	3.87e-17	3.41e-15	266
GO:004670015	Oral cavity	OSCC	heterocycle catabolic process	254/7305	445/18723	5.07e-15	3.31e-13	254
GO:001907920	Oral cavity	OSCC	viral genome replication	95/7305	131/18723	6.35e-15	4.02e-13	95
GO:004427016	Oral cavity	OSCC	cellular nitrogen compound catabolic process	256/7305	451/18723	9.67e-15	5.88e-13	256
GO:001943915	Oral cavity	OSCC	aromatic compound catabolic process	263/7305	467/18723	1.49e-14	8.84e-13	263
GO:000961515	Oral cavity	OSCC	response to virus	215/7305	367/18723	1.63e-14	9.41e-13	215
GO:005109820	Oral cavity	OSCC	regulation of binding	212/7305	363/18723	3.88e-14	2.15e-12	212
GO:190136115	Oral cavity	OSCC	organic cyclic compound catabolic process	272/7305	495/18723	2.73e-13	1.36e-11	272
GO:00062603	Oral cavity	OSCC	DNA replication	159/7305	260/18723	3.25e-13	1.59e-11	159
GO:005105210	Oral cavity	OSCC	regulation of DNA metabolic process	207/7305	359/18723	4.45e-13	2.17e-11	207
GO:004440320	Oral cavity	OSCC	biological process involved in symbiotic interaction	173/7305	290/18723	6.80e-13	3.19e-11	173
GO:005079220	Oral cavity	OSCC	regulation of viral process	109/7305	164/18723	8.95e-13	4.10e-11	109
GO:00102128	Oral cavity	OSCC	response to ionizing radiation	99/7305	148/18723	5.49e-12	2.08e-10	99
GO:000756818	Oral cavity	OSCC	aging	194/7305	339/18723	6.18e-12	2.33e-10	194
GO:000170116	Oral cavity	OSCC	in utero embryonic development	207/7305	367/18723	7.92e-12	2.95e-10	207
GO:001908010	Oral cavity	OSCC	viral gene expression	69/7305	94/18723	1.26e-11	4.44e-10	69

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
MGA	CD8TEFF	Breast	ADJ	NUP107,TUBGCP2,HIST2H2AC, etc.	1.77e-01
MGA	CD8TEXINT	Breast	DCIS	NUP107,TUBGCP2,HIST2H2AC, etc.	1.50e-01
MGA	CD8TEFF	Breast	DCIS	NUP107,TUBGCP2,HIST2H2AC, etc.	1.27e-01
MGA	CD8TEFF	Breast	Healthy	NUP107,TUBGCP2,HIST2H2AC, etc.	6.35e-02
MGA	CD8TEFF	Breast	IDC	NUP107,TUBGCP2,HIST2H2AC, etc.	9.26e-02
MGA	TH1	Colorectum	MSI-H	PARP9,WDFY1,MRPS9, etc.	2.42e-02
MGA	PERI	Colorectum	MSI-H	ERO1B,POLG,RFC3, etc.	2.53e-01
MGA	CD8TEFF	Lung	AAH	HEXIM1,ST8SIA6,PTPRA, etc.	1.97e-01
MGA	NEUT	Lung	AIS	AC010260.1,LNX2,AP002762.2, etc.	1.80e-02
MGA	CD8TEXP	Oral cavity	EOLP	TYW1B,MBNL3,ZNF266, etc.	1.80e-01

∗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

MGA

SNV

Missense_Mutation

c.7534N>G

p.Lys2512Glu

p.K2512E

Q8IWI9

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-A1-A0SE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MGA

SNV

Missense_Mutation

rs367727094

c.4180N>T

p.Arg1394Cys

p.R1394C

Q8IWI9

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-A1-A0SN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

MGA

SNV

Missense_Mutation

novel

c.7933T>G

p.Leu2645Val

p.L2645V

Q8IWI9

protein_coding

tolerated(0.16)

possibly_damaging(0.76)

TCGA-A7-A5ZX-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

MGA

SNV

Missense_Mutation

c.1279C>G

p.Leu427Val

p.L427V

Q8IWI9

protein_coding

deleterious(0.03)

probably_damaging(0.94)

TCGA-A8-A082-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

MGA

SNV

Missense_Mutation

novel

c.4252N>C

p.Asp1418His

p.D1418H

Q8IWI9

protein_coding

deleterious(0)

probably_damaging(0.921)

TCGA-A8-A08L-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

MGA

SNV

Missense_Mutation

rs773922303

c.2789C>G

p.Ser930Cys

p.S930C

Q8IWI9

protein_coding

deleterious(0)

benign(0.009)

TCGA-A8-A09I-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

MGA

SNV

Missense_Mutation

c.7384C>G

p.Leu2462Val

p.L2462V

Q8IWI9

protein_coding

deleterious(0.04)

benign(0.366)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MGA

SNV

Missense_Mutation

novel

c.1663G>A

p.Asp555Asn

p.D555N

Q8IWI9

protein_coding

tolerated_low_confidence(0.62)

benign(0.046)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

MGA

SNV

Missense_Mutation

novel

c.7330G>A

p.Glu2444Lys

p.E2444K

Q8IWI9

protein_coding

deleterious(0.04)

probably_damaging(0.98)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

MGA

SNV

Missense_Mutation

novel

c.383C>A

p.Ser128Tyr

p.S128Y

Q8IWI9

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-AN-A046-01

Breast

breast invasive 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
23269	MGA	TRANSCRIPTION FACTOR	inhibitor	CHEMBL1561	MIGLITOL
23269	MGA	TRANSCRIPTION FACTOR	inhibitor	CHEMBL1566	ACARBOSE

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