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: MACF1

Gene summary for MACF1

Gene summary.

Gene information	Species	Human
	Gene symbol	MACF1
	Gene ID	23499
	Gene name	microtubule actin crosslinking factor 1
	Gene Alias	ABP620
	Cytomap	1p34.3
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	Q6ZSD7

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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
23499	MACF1	CA_HPV_1	Human	Cervix	CC	1.75e-09	-6.32e-03	0.0264
23499	MACF1	CA_HPV_2	Human	Cervix	CC	3.26e-04	2.58e-01	0.0391
23499	MACF1	CA_HPV_3	Human	Cervix	CC	3.75e-06	1.95e-01	0.0414
23499	MACF1	CCI_1	Human	Cervix	CC	3.10e-07	1.90e+00	0.528
23499	MACF1	CCI_3	Human	Cervix	CC	4.30e-07	8.53e-01	0.516
23499	MACF1	L1	Human	Cervix	CC	2.02e-03	-2.11e-01	0.0802
23499	MACF1	HTA11_3410_2000001011	Human	Colorectum	AD	5.53e-07	-5.00e-01	0.0155
23499	MACF1	HTA11_347_2000001011	Human	Colorectum	AD	1.58e-02	3.33e-01	-0.1954
23499	MACF1	HTA11_411_2000001011	Human	Colorectum	SER	7.52e-04	7.96e-01	-0.2602
23499	MACF1	HTA11_3361_2000001011	Human	Colorectum	AD	1.60e-06	-4.24e-01	-0.1207
23499	MACF1	HTA11_99999974143_84620	Human	Colorectum	MSS	3.32e-02	-2.85e-01	0.3005
23499	MACF1	A001-C-207	Human	Colorectum	FAP	1.19e-03	7.55e-02	0.1278
23499	MACF1	A015-C-203	Human	Colorectum	FAP	3.23e-32	-1.08e-01	-0.1294
23499	MACF1	A015-C-204	Human	Colorectum	FAP	5.53e-03	-3.77e-02	-0.0228
23499	MACF1	A014-C-040	Human	Colorectum	FAP	8.51e-03	-2.24e-01	-0.1184
23499	MACF1	A002-C-201	Human	Colorectum	FAP	7.61e-10	-5.76e-02	0.0324
23499	MACF1	A002-C-203	Human	Colorectum	FAP	7.70e-04	-2.80e-02	0.2786
23499	MACF1	A001-C-119	Human	Colorectum	FAP	9.67e-17	3.38e-01	-0.1557
23499	MACF1	A001-C-108	Human	Colorectum	FAP	2.71e-18	2.76e-01	-0.0272
23499	MACF1	A002-C-205	Human	Colorectum	FAP	6.91e-27	6.46e-02	-0.1236

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:004592722	Oral cavity	NEOLP	positive regulation of growth	45/2005	259/18723	7.42e-04	6.05e-03	45
GO:004858822	Oral cavity	NEOLP	developmental cell growth	41/2005	234/18723	1.05e-03	8.00e-03	41
GO:003030721	Oral cavity	NEOLP	positive regulation of cell growth	31/2005	166/18723	1.45e-03	1.03e-02	31
GO:005196012	Oral cavity	NEOLP	regulation of nervous system development	68/2005	443/18723	1.46e-03	1.03e-02	68
GO:005077221	Oral cavity	NEOLP	positive regulation of axonogenesis	18/2005	79/18723	1.46e-03	1.03e-02	18
GO:009887631	Oral cavity	NEOLP	vesicle-mediated transport to the plasma membrane	26/2005	136/18723	2.40e-03	1.53e-02	26
GO:004863814	Oral cavity	NEOLP	regulation of developmental growth	51/2005	330/18723	4.64e-03	2.56e-02	51
GO:004863913	Oral cavity	NEOLP	positive regulation of developmental growth	30/2005	174/18723	5.83e-03	3.04e-02	30
GO:000836121	Oral cavity	NEOLP	regulation of cell size	30/2005	181/18723	1.02e-02	4.76e-02	30
GO:004819310	Prostate	BPH	Golgi vesicle transport	102/3107	296/18723	3.90e-14	4.56e-12	102
GO:015011515	Prostate	BPH	cell-substrate junction organization	49/3107	101/18723	9.49e-14	1.01e-11	49
GO:000704410	Prostate	BPH	cell-substrate junction assembly	46/3107	95/18723	5.89e-13	5.21e-11	46
GO:001604910	Prostate	BPH	cell growth	139/3107	482/18723	7.53e-12	5.90e-10	139
GO:002260417	Prostate	BPH	regulation of cell morphogenesis	99/3107	309/18723	1.30e-11	9.72e-10	99
GO:003158910	Prostate	BPH	cell-substrate adhesion	110/3107	363/18723	4.64e-11	2.96e-09	110
GO:004206018	Prostate	BPH	wound healing	123/3107	422/18723	5.74e-11	3.59e-09	123
GO:015011615	Prostate	BPH	regulation of cell-substrate junction organization	35/3107	71/18723	1.81e-10	1.02e-08	35
GO:00160559	Prostate	BPH	Wnt signaling pathway	126/3107	444/18723	2.27e-10	1.23e-08	126
GO:01987389	Prostate	BPH	cell-cell signaling by wnt	126/3107	446/18723	3.11e-10	1.67e-08	126
GO:007265916	Prostate	BPH	protein localization to plasma membrane	89/3107	284/18723	5.00e-10	2.56e-08	89

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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

MACF1

SNV

Missense_Mutation

novel

c.7798N>G

p.Gln2600Glu

p.Q2600E

Q9UPN3

protein_coding

tolerated(0.13)

benign(0.006)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

MACF1

SNV

Missense_Mutation

c.8631N>C

p.Glu2877Asp

p.E2877D

Q9UPN3

protein_coding

tolerated(0.1)

benign(0.054)

TCGA-A2-A0CQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

MACF1

SNV

Missense_Mutation

rs761570070

c.14837N>A

p.Arg4946Gln

p.R4946Q

Q9UPN3

protein_coding

deleterious(0)

probably_damaging(0.964)

TCGA-A7-A0CD-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

MACF1

SNV

Missense_Mutation

novel

c.6629N>T

p.Thr2210Ile

p.T2210I

Q9UPN3

protein_coding

deleterious(0.04)

benign(0.211)

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

MACF1

SNV

Missense_Mutation

c.14091N>T

p.Lys4697Asn

p.K4697N

Q9UPN3

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A8-A094-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MACF1

SNV

Missense_Mutation

novel

c.13989G>T

p.Lys4663Asn

p.K4663N

Q9UPN3

protein_coding

tolerated(0.07)

probably_damaging(0.999)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MACF1

SNV

Missense_Mutation

rs749774177

c.14554N>A

p.Asp4852Asn

p.D4852N

Q9UPN3

protein_coding

tolerated(0.08)

probably_damaging(0.937)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MACF1

SNV

Missense_Mutation

c.12536N>A

p.Cys4179Tyr

p.C4179Y

Q9UPN3

protein_coding

deleterious(0.04)

probably_damaging(0.999)

TCGA-AN-A0XN-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

MACF1

SNV

Missense_Mutation

c.470N>A

p.Arg157His

p.R157H

Q9UPN3

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

MACF1

SNV

Missense_Mutation

novel

c.5482N>C

p.Glu1828Gln

p.E1828Q

Q9UPN3

protein_coding

tolerated(0.06)

possibly_damaging(0.521)

TCGA-BH-A0B6-01

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

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