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: MTCH1

Gene summary for MTCH1

Gene summary.

Gene information	Species	Human
	Gene symbol	MTCH1
	Gene ID	23787
	Gene name	mitochondrial carrier 1
	Gene Alias	CGI-64
	Cytomap	6p21.2
	Gene Type	protein-coding
	GO ID	GO:0006508
	UniProtAcc	A0A024RCX4

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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
23787	MTCH1	P10_cSCC	Human	Skin	cSCC	1.75e-11	7.04e-01	0.1017
23787	MTCH1	cSCC_p7	Human	Skin	cSCC	3.52e-03	-3.23e-01	-0.2332
23787	MTCH1	cSCC_p8	Human	Skin	cSCC	2.77e-05	-8.83e-02	-0.1971
23787	MTCH1	cSCC_p9	Human	Skin	cSCC	5.66e-03	-3.50e-02	-0.1991
23787	MTCH1	Adj_PTCwithHT_6	Human	Thyroid	HT	8.07e-04	-3.60e-01	0.02
23787	MTCH1	PTCwithHT_1	Human	Thyroid	HT	6.80e-05	-5.58e-01	0.0238
23787	MTCH1	male-WTA	Human	Thyroid	PTC	4.86e-66	7.04e-01	0.1037
23787	MTCH1	nodule-WTA	Human	Thyroid	goiters	6.21e-08	7.04e-01	0.0534
23787	MTCH1	PTC01	Human	Thyroid	PTC	2.97e-13	7.70e-01	0.1899
23787	MTCH1	PTC04	Human	Thyroid	PTC	3.97e-33	1.11e+00	0.1927
23787	MTCH1	PTC05	Human	Thyroid	PTC	1.14e-19	1.67e+00	0.2065
23787	MTCH1	PTC06	Human	Thyroid	PTC	7.27e-62	2.45e+00	0.2057
23787	MTCH1	PTC07	Human	Thyroid	PTC	2.95e-89	1.84e+00	0.2044
23787	MTCH1	ATC08	Human	Thyroid	ATC	1.68e-15	-1.65e-01	0.0541
23787	MTCH1	ATC09	Human	Thyroid	ATC	5.24e-05	3.61e-01	0.2871
23787	MTCH1	ATC12	Human	Thyroid	ATC	1.35e-10	4.92e-01	0.34
23787	MTCH1	ATC13	Human	Thyroid	ATC	2.21e-85	2.94e+00	0.34
23787	MTCH1	ATC1	Human	Thyroid	ATC	1.05e-04	4.82e-01	0.2878
23787	MTCH1	ATC2	Human	Thyroid	ATC	7.82e-13	1.68e+00	0.34
23787	MTCH1	ATC3	Human	Thyroid	ATC	5.20e-07	2.60e-02	0.338

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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:0045862	Colorectum	AD	positive regulation of proteolysis	129/3918	372/18723	4.04e-10	3.46e-08	129
GO:0043281	Colorectum	AD	regulation of cysteine-type endopeptidase activity involved in apoptotic process	72/3918	209/18723	3.70e-06	1.03e-04	72
GO:2000116	Colorectum	AD	regulation of cysteine-type endopeptidase activity	79/3918	235/18723	3.74e-06	1.03e-04	79
GO:0052547	Colorectum	AD	regulation of peptidase activity	137/3918	461/18723	4.12e-06	1.12e-04	137
GO:0010952	Colorectum	AD	positive regulation of peptidase activity	68/3918	197/18723	6.30e-06	1.59e-04	68
GO:0052548	Colorectum	AD	regulation of endopeptidase activity	124/3918	432/18723	6.58e-05	1.07e-03	124
GO:0010950	Colorectum	AD	positive regulation of endopeptidase activity	59/3918	179/18723	1.11e-04	1.65e-03	59
GO:2001056	Colorectum	AD	positive regulation of cysteine-type endopeptidase activity	47/3918	148/18723	1.30e-03	1.14e-02	47
GO:0043280	Colorectum	AD	positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	42/3918	129/18723	1.33e-03	1.16e-02	42
GO:00458621	Colorectum	SER	positive regulation of proteolysis	106/2897	372/18723	8.40e-11	1.20e-08	106
GO:00525471	Colorectum	SER	regulation of peptidase activity	114/2897	461/18723	1.18e-07	7.17e-06	114
GO:00525481	Colorectum	SER	regulation of endopeptidase activity	103/2897	432/18723	2.86e-06	1.16e-04	103
GO:00109521	Colorectum	SER	positive regulation of peptidase activity	55/2897	197/18723	5.44e-06	2.00e-04	55
GO:00432811	Colorectum	SER	regulation of cysteine-type endopeptidase activity involved in apoptotic process	57/2897	209/18723	8.08e-06	2.74e-04	57
GO:20001161	Colorectum	SER	regulation of cysteine-type endopeptidase activity	62/2897	235/18723	1.05e-05	3.39e-04	62
GO:00109501	Colorectum	SER	positive regulation of endopeptidase activity	47/2897	179/18723	1.32e-04	2.66e-03	47
GO:00432801	Colorectum	SER	positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	33/2897	129/18723	1.97e-03	1.97e-02	33
GO:20010561	Colorectum	SER	positive regulation of cysteine-type endopeptidase activity	36/2897	148/18723	3.21e-03	2.76e-02	36
GO:0006919	Colorectum	SER	activation of cysteine-type endopeptidase activity involved in apoptotic process	21/2897	78/18723	6.50e-03	4.66e-02	21
GO:00458622	Colorectum	MSS	positive regulation of proteolysis	119/3467	372/18723	2.14e-10	2.09e-08	119

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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

MTCH1

SNV

Missense_Mutation

c.1070T>C

p.Ile357Thr

p.I357T

Q9NZJ7

protein_coding

tolerated(0.11)

possibly_damaging(0.702)

TCGA-D8-A147-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

MTCH1

SNV

Missense_Mutation

c.901N>G

p.Ser301Ala

p.S301A

Q9NZJ7

protein_coding

tolerated_low_confidence(0.12)

benign(0.18)

TCGA-D8-A1Y3-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicine+cyclophosphamide

MTCH1

insertion

Frame_Shift_Ins

novel

c.961_962insCAGTACCAACCTTGGGTTCTCGTGTTCTG

p.Val321AlafsTer11

p.V321Afs*11

Q9NZJ7

protein_coding

TCGA-A7-A0CD-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

MTCH1

SNV

Missense_Mutation

c.182N>T

p.Ser61Leu

p.S61L

Q9NZJ7

protein_coding

deleterious_low_confidence(0.05)

benign(0.025)

TCGA-VS-A958-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MTCH1

SNV

Missense_Mutation

novel

c.685N>T

p.Arg229Trp

p.R229W

Q9NZJ7

protein_coding

tolerated(0.07)

benign(0.04)

TCGA-AA-3966-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

MTCH1

SNV

Missense_Mutation

novel

c.902C>T

p.Ser301Phe

p.S301F

Q9NZJ7

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.477)

TCGA-AA-A00N-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

MTCH1

SNV

Missense_Mutation

c.1068N>T

p.Trp356Cys

p.W356C

Q9NZJ7

protein_coding

deleterious(0)

possibly_damaging(0.584)

TCGA-DM-A28C-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

MTCH1

SNV

Missense_Mutation

c.1133G>A

p.Arg378His

p.R378H

Q9NZJ7

protein_coding

tolerated(0.06)

benign(0.009)

TCGA-NH-A5IV-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

MTCH1

SNV

Missense_Mutation

novel

c.1072N>T

p.His358Tyr

p.H358Y

Q9NZJ7

protein_coding

deleterious(0.02)

possibly_damaging(0.651)

TCGA-A5-A0G1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

MTCH1

SNV

Missense_Mutation

c.871G>T

p.Gly291Trp

p.G291W

Q9NZJ7

protein_coding

deleterious_low_confidence(0.01)

benign(0.157)

TCGA-AP-A059-01

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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