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: MAP4

Gene summary for MAP4

Gene summary.

Gene information	Species	Human
	Gene symbol	MAP4
	Gene ID	4134
	Gene name	microtubule associated protein 4
	Gene Alias	MAP4
	Cytomap	3p21.31
	Gene Type	protein-coding
	GO ID	GO:0000226
	UniProtAcc	P27816

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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
4134	MAP4	P75T-E	Human	Esophagus	ESCC	2.68e-25	5.76e-01	0.1125
4134	MAP4	P76T-E	Human	Esophagus	ESCC	9.10e-19	3.99e-01	0.1207
4134	MAP4	P79T-E	Human	Esophagus	ESCC	3.99e-18	4.85e-01	0.1154
4134	MAP4	P80T-E	Human	Esophagus	ESCC	9.10e-24	9.78e-01	0.155
4134	MAP4	P82T-E	Human	Esophagus	ESCC	2.48e-07	7.40e-01	0.1072
4134	MAP4	P83T-E	Human	Esophagus	ESCC	3.11e-42	1.34e+00	0.1738
4134	MAP4	P84T-E	Human	Esophagus	ESCC	3.05e-02	5.24e-01	0.0933
4134	MAP4	P89T-E	Human	Esophagus	ESCC	4.18e-09	1.19e+00	0.1752
4134	MAP4	P91T-E	Human	Esophagus	ESCC	4.39e-12	1.74e+00	0.1828
4134	MAP4	P104T-E	Human	Esophagus	ESCC	2.20e-02	4.41e-01	0.0931
4134	MAP4	P107T-E	Human	Esophagus	ESCC	1.25e-39	1.32e+00	0.171
4134	MAP4	P126T-E	Human	Esophagus	ESCC	1.70e-07	1.23e+00	0.1125
4134	MAP4	P127T-E	Human	Esophagus	ESCC	1.61e-19	2.58e-01	0.0826
4134	MAP4	P128T-E	Human	Esophagus	ESCC	1.08e-24	9.31e-01	0.1241
4134	MAP4	P130T-E	Human	Esophagus	ESCC	1.39e-53	1.16e+00	0.1676
4134	MAP4	S43	Human	Liver	Cirrhotic	7.02e-07	-2.45e-02	-0.0187
4134	MAP4	HCC1_Meng	Human	Liver	HCC	5.86e-76	-5.06e-05	0.0246
4134	MAP4	HCC2_Meng	Human	Liver	HCC	8.52e-26	-1.09e-01	0.0107
4134	MAP4	cirrhotic1	Human	Liver	Cirrhotic	2.44e-04	5.89e-02	0.0202
4134	MAP4	cirrhotic2	Human	Liver	Cirrhotic	2.66e-08	6.09e-02	0.0201

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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
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:00071639	Cervix	CC	establishment or maintenance of cell polarity	63/2311	218/18723	4.25e-11	8.76e-09	63
GO:00300108	Cervix	CC	establishment of cell polarity	42/2311	143/18723	4.30e-08	2.62e-06	42
GO:00310988	Cervix	CC	stress-activated protein kinase signaling cascade	58/2311	247/18723	8.02e-07	2.89e-05	58
GO:00514038	Cervix	CC	stress-activated MAPK cascade	55/2311	239/18723	2.96e-06	8.31e-05	55
GO:00346129	Cervix	CC	response to tumor necrosis factor	55/2311	253/18723	1.75e-05	3.32e-04	55
GO:00516567	Cervix	CC	establishment of organelle localization	76/2311	390/18723	3.17e-05	5.21e-04	76
GO:00093149	Cervix	CC	response to radiation	86/2311	456/18723	3.50e-05	5.63e-04	86
GO:00106399	Cervix	CC	negative regulation of organelle organization	68/2311	348/18723	7.40e-05	1.03e-03	68
GO:19021153	Cervix	CC	regulation of organelle assembly	40/2311	186/18723	2.92e-04	3.15e-03	40
GO:00094112	Cervix	CC	response to UV	33/2311	149/18723	5.51e-04	5.29e-03	33
GO:00313456	Cervix	CC	negative regulation of cell projection organization	39/2311	186/18723	5.86e-04	5.57e-03	39
GO:00072545	Cervix	CC	JNK cascade	35/2311	167/18723	1.10e-03	9.09e-03	35
GO:01200328	Cervix	CC	regulation of plasma membrane bounded cell projection assembly	38/2311	186/18723	1.14e-03	9.35e-03	38
GO:00604917	Cervix	CC	regulation of cell projection assembly	38/2311	188/18723	1.40e-03	1.10e-02	38
GO:00094163	Cervix	CC	response to light stimulus	54/2311	320/18723	1.03e-02	4.97e-02	54
GO:0051656	Colorectum	AD	establishment of organelle localization	131/3918	390/18723	3.00e-09	2.06e-07	131
GO:0010639	Colorectum	AD	negative regulation of organelle organization	114/3918	348/18723	1.41e-07	6.49e-06	114
GO:0007163	Colorectum	AD	establishment or maintenance of cell polarity	77/3918	218/18723	5.72e-07	2.08e-05	77
GO:0030010	Colorectum	AD	establishment of cell polarity	50/3918	143/18723	6.90e-05	1.11e-03	50
GO:0007051	Colorectum	AD	spindle organization	58/3918	184/18723	4.71e-04	5.20e-03	58

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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

MAP4

SNV

Missense_Mutation

novel

c.3131A>G

p.Asn1044Ser

p.N1044S

P27816

protein_coding

deleterious(0.01)

possibly_damaging(0.641)

TCGA-AR-A5QQ-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

carboplatin

MAP4

SNV

Missense_Mutation

c.71A>G

p.Asp24Gly

p.D24G

P27816

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MAP4

insertion

In_Frame_Ins

novel

c.3410_3411insCTTACTGTCCAAAACTACAAGGACAGTGACAGTTCTGACAGG

p.Gln1137delinsHisLeuLeuSerLysThrThrArgThrValThrValLeuThrGly

p.Q1137delinsHLLSKTTRTVTVLTG

P27816

protein_coding

TCGA-A8-A0A2-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

MAP4

insertion

Nonsense_Mutation

novel

c.2692_2693insACTGCATATAGTGATGGAGAAAGATCACAGT

p.Pro898HisfsTer4

p.P898Hfs*4

P27816

protein_coding

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

MAP4

SNV

Missense_Mutation

novel

c.1241N>T

p.Ser414Leu

p.S414L

P27816

protein_coding

deleterious(0)

possibly_damaging(0.656)

TCGA-DS-A5RQ-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

MAP4

SNV

Missense_Mutation

novel

c.2122N>G

p.Gln708Glu

p.Q708E

P27816

protein_coding

deleterious(0.04)

benign(0.328)

TCGA-EK-A2RJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MAP4

SNV

Missense_Mutation

c.3155G>A

p.Gly1052Glu

p.G1052E

P27816

protein_coding

deleterious(0)

probably_damaging(0.973)

TCGA-EK-A2RK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

MAP4

SNV

Missense_Mutation

c.2968G>T

p.Gly990Trp

p.G990W

P27816

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-MU-A5YI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MAP4

SNV

Missense_Mutation

novel

c.2544G>C

p.Lys848Asn

p.K848N

P27816

protein_coding

deleterious(0)

probably_damaging(0.928)

TCGA-VS-A94X-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MAP4

SNV

Missense_Mutation

novel

c.478G>T

p.Ala160Ser

p.A160S

P27816

protein_coding

tolerated(0.13)

benign(0.039)

TCGA-5M-AATE-01

Colorectum

colon adenocarcinoma

Male

>=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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