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: MICAL3

Gene summary for MICAL3

Gene summary.

Gene information	Species	Human
	Gene symbol	MICAL3
	Gene ID	57553
	Gene name	microtubule associated monooxygenase, calponin and LIM domain containing 3
	Gene Alias	MICAL-3
	Cytomap	22q11.21
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	Q7RTP6

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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
57553	MICAL3	P80T-E	Human	Esophagus	ESCC	6.96e-12	3.33e-01	0.155
57553	MICAL3	P82T-E	Human	Esophagus	ESCC	5.97e-09	3.44e-01	0.1072
57553	MICAL3	P83T-E	Human	Esophagus	ESCC	3.22e-27	6.72e-01	0.1738
57553	MICAL3	P84T-E	Human	Esophagus	ESCC	3.37e-09	3.45e-01	0.0933
57553	MICAL3	P89T-E	Human	Esophagus	ESCC	6.02e-08	6.16e-01	0.1752
57553	MICAL3	P91T-E	Human	Esophagus	ESCC	2.10e-19	1.09e+00	0.1828
57553	MICAL3	P104T-E	Human	Esophagus	ESCC	2.70e-02	1.59e-01	0.0931
57553	MICAL3	P107T-E	Human	Esophagus	ESCC	1.00e-36	7.25e-01	0.171
57553	MICAL3	P127T-E	Human	Esophagus	ESCC	1.56e-02	7.62e-02	0.0826
57553	MICAL3	P128T-E	Human	Esophagus	ESCC	1.58e-15	4.70e-01	0.1241
57553	MICAL3	P130T-E	Human	Esophagus	ESCC	1.70e-53	9.50e-01	0.1676
57553	MICAL3	NAFLD1	Human	Liver	NAFLD	2.09e-08	8.07e-01	-0.04
57553	MICAL3	S43	Human	Liver	Cirrhotic	2.92e-02	-6.42e-04	-0.0187
57553	MICAL3	HCC1_Meng	Human	Liver	HCC	1.98e-41	-4.94e-02	0.0246
57553	MICAL3	HCC2_Meng	Human	Liver	HCC	2.58e-07	-5.35e-02	0.0107
57553	MICAL3	HCC1	Human	Liver	HCC	8.11e-05	2.08e+00	0.5336
57553	MICAL3	HCC2	Human	Liver	HCC	2.29e-12	2.85e+00	0.5341
57553	MICAL3	HCC5	Human	Liver	HCC	2.48e-03	2.59e+00	0.4932
57553	MICAL3	S027	Human	Liver	HCC	4.51e-04	4.64e-01	0.2446
57553	MICAL3	S028	Human	Liver	HCC	8.03e-10	4.79e-01	0.2503

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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
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
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:000701510	Cervix	CC	actin filament organization	109/2311	442/18723	4.92e-13	2.45e-10	109
GO:00081549	Cervix	CC	actin polymerization or depolymerization	51/2311	218/18723	4.05e-06	1.05e-04	51
GO:002241110	Cervix	CC	cellular component disassembly	83/2311	443/18723	6.04e-05	8.68e-04	83
GO:00329847	Cervix	CC	protein-containing complex disassembly	41/2311	224/18723	6.13e-03	3.48e-02	41
GO:00068873	Cervix	CC	exocytosis	59/2311	352/18723	8.74e-03	4.48e-02	59
GO:0007015	Colorectum	AD	actin filament organization	167/3918	442/18723	1.65e-16	7.94e-14	167
GO:0008154	Colorectum	AD	actin polymerization or depolymerization	90/3918	218/18723	6.14e-12	8.23e-10	90
GO:0022411	Colorectum	AD	cellular component disassembly	147/3918	443/18723	8.53e-10	6.76e-08	147
GO:0032984	Colorectum	AD	protein-containing complex disassembly	81/3918	224/18723	9.41e-08	4.65e-06	81
GO:0030042	Colorectum	AD	actin filament depolymerization	27/3918	59/18723	1.65e-05	3.47e-04	27
GO:0043624	Colorectum	AD	cellular protein complex disassembly	45/3918	136/18723	6.24e-04	6.48e-03	45
GO:0051261	Colorectum	AD	protein depolymerization	39/3918	114/18723	6.74e-04	6.91e-03	39
GO:0006887	Colorectum	AD	exocytosis	96/3918	352/18723	2.48e-03	1.90e-02	96
GO:00070152	Colorectum	MSS	actin filament organization	146/3467	442/18723	1.16e-13	2.67e-11	146
GO:00081542	Colorectum	MSS	actin polymerization or depolymerization	79/3467	218/18723	4.14e-10	3.49e-08	79
GO:00224112	Colorectum	MSS	cellular component disassembly	130/3467	443/18723	1.44e-08	8.46e-07	130
GO:00329842	Colorectum	MSS	protein-containing complex disassembly	69/3467	224/18723	5.61e-06	1.50e-04	69
GO:00300422	Colorectum	MSS	actin filament depolymerization	22/3467	59/18723	5.35e-04	6.02e-03	22
GO:00070154	Colorectum	FAP	actin filament organization	125/2622	442/18723	1.97e-15	3.03e-12	125
GO:00081544	Colorectum	FAP	actin polymerization or depolymerization	60/2622	218/18723	1.15e-07	7.43e-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

MICAL3

SNV

Missense_Mutation

rs770532587

c.2119N>G

p.Leu707Val

p.L707V

Q7RTP6

protein_coding

tolerated_low_confidence(0.13)

benign(0.418)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

MICAL3

SNV

Missense_Mutation

novel

c.2977N>C

p.Glu993Gln

p.E993Q

Q7RTP6

protein_coding

deleterious_low_confidence(0.04)

benign(0.422)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

MICAL3

SNV

Missense_Mutation

novel

c.755G>A

p.Arg252Gln

p.R252Q

Q7RTP6

protein_coding

deleterious(0)

possibly_damaging(0.859)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MICAL3

SNV

Missense_Mutation

c.639N>T

p.Glu213Asp

p.E213D

Q7RTP6

protein_coding

tolerated(0.2)

probably_damaging(0.97)

TCGA-AO-A03O-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

MICAL3

SNV

Missense_Mutation

c.4886N>T

p.Ala1629Val

p.A1629V

Q7RTP6

protein_coding

tolerated_low_confidence(0.06)

benign(0.003)

TCGA-BH-A0AU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MICAL3

SNV

Missense_Mutation

novel

c.3671N>C

p.Arg1224Pro

p.R1224P

Q7RTP6

protein_coding

tolerated_low_confidence(0.1)

benign(0.301)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MICAL3

SNV

Missense_Mutation

c.1432T>C

p.Phe478Leu

p.F478L

Q7RTP6

protein_coding

tolerated(0.16)

benign(0.444)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

MICAL3

SNV

Missense_Mutation

rs201688866

c.4343N>T

p.Ser1448Leu

p.S1448L

Q7RTP6

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.988)

TCGA-EW-A3E8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

anastrozole

MICAL3

SNV

Missense_Mutation

novel

c.3904N>C

p.Ser1302Arg

p.S1302R

Q7RTP6

protein_coding

tolerated_low_confidence(0.05)

benign(0)

TCGA-OL-A5RW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

MICAL3

insertion

Frame_Shift_Ins

novel

c.421_422insTATCTAGAGATGGTCCT

p.Gly141ValfsTer30

p.G141Vfs*30

Q7RTP6

protein_coding

TCGA-A8-A0A4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

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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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