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: MCUR1

Gene summary for MCUR1

Gene summary.

Gene information	Species	Human
	Gene symbol	MCUR1
	Gene ID	63933
	Gene name	mitochondrial calcium uniporter regulator 1
	Gene Alias	C6orf79
	Cytomap	6p23
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	Q96AQ8

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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
63933	MCUR1	LZE2T	Human	Esophagus	ESCC	1.09e-02	4.81e-01	0.082
63933	MCUR1	LZE4T	Human	Esophagus	ESCC	4.18e-17	4.28e-01	0.0811
63933	MCUR1	LZE7T	Human	Esophagus	ESCC	2.43e-04	4.79e-01	0.0667
63933	MCUR1	LZE20T	Human	Esophagus	ESCC	1.07e-02	2.06e-01	0.0662
63933	MCUR1	LZE22D1	Human	Esophagus	HGIN	1.46e-03	1.83e-01	0.0595
63933	MCUR1	LZE22T	Human	Esophagus	ESCC	1.98e-03	7.10e-01	0.068
63933	MCUR1	LZE24T	Human	Esophagus	ESCC	4.16e-16	4.24e-01	0.0596
63933	MCUR1	LZE21T	Human	Esophagus	ESCC	1.08e-08	3.83e-01	0.0655
63933	MCUR1	P1T-E	Human	Esophagus	ESCC	9.49e-17	6.50e-01	0.0875
63933	MCUR1	P2T-E	Human	Esophagus	ESCC	1.30e-50	1.03e+00	0.1177
63933	MCUR1	P4T-E	Human	Esophagus	ESCC	4.93e-44	1.15e+00	0.1323
63933	MCUR1	P5T-E	Human	Esophagus	ESCC	1.02e-36	6.97e-01	0.1327
63933	MCUR1	P8T-E	Human	Esophagus	ESCC	3.85e-24	3.24e-01	0.0889
63933	MCUR1	P9T-E	Human	Esophagus	ESCC	2.87e-25	7.57e-01	0.1131
63933	MCUR1	P10T-E	Human	Esophagus	ESCC	2.12e-60	1.13e+00	0.116
63933	MCUR1	P11T-E	Human	Esophagus	ESCC	1.92e-29	1.25e+00	0.1426
63933	MCUR1	P12T-E	Human	Esophagus	ESCC	8.71e-52	8.57e-01	0.1122
63933	MCUR1	P15T-E	Human	Esophagus	ESCC	1.23e-30	7.91e-01	0.1149
63933	MCUR1	P16T-E	Human	Esophagus	ESCC	1.06e-36	6.55e-01	0.1153
63933	MCUR1	P17T-E	Human	Esophagus	ESCC	3.99e-24	1.11e+00	0.1278

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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:000683920	Esophagus	HGIN	mitochondrial transport	74/2587	254/18723	1.32e-10	1.32e-08	74
GO:199054220	Esophagus	HGIN	mitochondrial transmembrane transport	29/2587	102/18723	8.52e-05	1.87e-03	29
GO:0006839110	Esophagus	ESCC	mitochondrial transport	187/8552	254/18723	8.35e-20	9.81e-18	187
GO:1990542110	Esophagus	ESCC	mitochondrial transmembrane transport	72/8552	102/18723	2.94e-07	4.23e-06	72
GO:00068397	Liver	Cirrhotic	mitochondrial transport	112/4634	254/18723	1.03e-11	6.66e-10	112
GO:005156011	Liver	Cirrhotic	mitochondrial calcium ion homeostasis	15/4634	26/18723	3.43e-04	2.93e-03	15
GO:19905425	Liver	Cirrhotic	mitochondrial transmembrane transport	41/4634	102/18723	4.08e-04	3.37e-03	41
GO:005156111	Liver	Cirrhotic	positive regulation of mitochondrial calcium ion concentration	8/4634	11/18723	1.10e-03	7.64e-03	8
GO:00364444	Liver	Cirrhotic	calcium import into the mitochondrion	8/4634	14/18723	9.65e-03	4.35e-02	8
GO:000683912	Liver	HCC	mitochondrial transport	184/7958	254/18723	2.30e-22	3.83e-20	184
GO:199054212	Liver	HCC	mitochondrial transmembrane transport	78/7958	102/18723	2.73e-12	1.26e-10	78
GO:003644411	Liver	HCC	calcium import into the mitochondrion	13/7958	14/18723	1.25e-04	1.03e-03	13
GO:005156021	Liver	HCC	mitochondrial calcium ion homeostasis	20/7958	26/18723	3.82e-04	2.61e-03	20
GO:00068513	Liver	HCC	mitochondrial calcium ion transmembrane transport	16/7958	20/18723	7.15e-04	4.37e-03	16
GO:00515612	Liver	HCC	positive regulation of mitochondrial calcium ion concentration	10/7958	11/18723	1.30e-03	7.01e-03	10
GO:000683918	Oral cavity	OSCC	mitochondrial transport	162/7305	254/18723	8.96e-16	6.52e-14	162
GO:00515615	Oral cavity	OSCC	positive regulation of mitochondrial calcium ion concentration	10/7305	11/18723	5.78e-04	3.30e-03	10
GO:199054218	Oral cavity	OSCC	mitochondrial transmembrane transport	56/7305	102/18723	8.06e-04	4.32e-03	56
GO:00515607	Oral cavity	OSCC	mitochondrial calcium ion homeostasis	18/7305	26/18723	1.75e-03	8.28e-03	18
GO:00068514	Oral cavity	OSCC	mitochondrial calcium ion transmembrane transport	14/7305	20/18723	4.95e-03	1.94e-02	14

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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

MCUR1

SNV

Missense_Mutation

c.733G>C

p.Glu245Gln

p.E245Q

Q96AQ8

protein_coding

deleterious(0.02)

possibly_damaging(0.899)

TCGA-BH-A0DZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

MCUR1

insertion

Nonsense_Mutation

novel

c.562_563insCTTTTTAGGGTAGACTAGATTATGTGTT

p.Ile188ThrfsTer3

p.I188Tfs*3

Q96AQ8

protein_coding

TCGA-AQ-A04J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

MCUR1

SNV

Missense_Mutation

rs774710482

c.499G>A

p.Asp167Asn

p.D167N

Q96AQ8

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

MCUR1

SNV

Missense_Mutation

rs772379179

c.955N>A

p.Glu319Lys

p.E319K

Q96AQ8

protein_coding

deleterious(0)

possibly_damaging(0.856)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

MCUR1

SNV

Missense_Mutation

rs780710613

c.1066N>T

p.Arg356Cys

p.R356C

Q96AQ8

protein_coding

deleterious(0)

possibly_damaging(0.479)

TCGA-EI-6917-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

5fluorouracil+oxaciplatina+l-folinian

MCUR1

SNV

Missense_Mutation

rs145895773

c.674N>T

p.Ala225Val

p.A225V

Q96AQ8

protein_coding

tolerated(0.07)

probably_damaging(0.967)

TCGA-A5-A0GP-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

MCUR1

SNV

Missense_Mutation

rs145895773

c.674N>T

p.Ala225Val

p.A225V

Q96AQ8

protein_coding

tolerated(0.07)

probably_damaging(0.967)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

MCUR1

SNV

Missense_Mutation

rs762334997

c.452N>A

p.Arg151His

p.R151H

Q96AQ8

protein_coding

tolerated(0.77)

benign(0)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

MCUR1

SNV

Missense_Mutation

c.536N>A

p.Gly179Glu

p.G179E

Q96AQ8

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AP-A1DP-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

paclitaxel

MCUR1

SNV

Missense_Mutation

rs756791116

c.925C>T

p.Arg309Trp

p.R309W

Q96AQ8

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AP-A1DV-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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