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: MAP3K11

Gene summary for MAP3K11

Gene summary.

Gene information	Species	Human
	Gene symbol	MAP3K11
	Gene ID	4296
	Gene name	mitogen-activated protein kinase kinase kinase 11
	Gene Alias	MEKK11
	Cytomap	11q13.1
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	A0A024R5E6

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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
4296	MAP3K11	LZE8T	Human	Esophagus	ESCC	2.18e-05	8.49e-02	0.067
4296	MAP3K11	LZE20T	Human	Esophagus	ESCC	1.02e-14	8.25e-01	0.0662
4296	MAP3K11	LZE22D1	Human	Esophagus	HGIN	1.90e-02	9.61e-02	0.0595
4296	MAP3K11	LZE22T	Human	Esophagus	ESCC	3.91e-03	4.10e-01	0.068
4296	MAP3K11	LZE24T	Human	Esophagus	ESCC	2.10e-19	5.60e-01	0.0596
4296	MAP3K11	P1T-E	Human	Esophagus	ESCC	1.98e-10	8.84e-01	0.0875
4296	MAP3K11	P2T-E	Human	Esophagus	ESCC	7.07e-29	4.11e-01	0.1177
4296	MAP3K11	P4T-E	Human	Esophagus	ESCC	4.27e-16	5.25e-01	0.1323
4296	MAP3K11	P5T-E	Human	Esophagus	ESCC	7.72e-17	2.82e-01	0.1327
4296	MAP3K11	P8T-E	Human	Esophagus	ESCC	6.54e-34	6.17e-01	0.0889
4296	MAP3K11	P9T-E	Human	Esophagus	ESCC	1.53e-10	3.31e-01	0.1131
4296	MAP3K11	P10T-E	Human	Esophagus	ESCC	3.99e-27	5.65e-01	0.116
4296	MAP3K11	P11T-E	Human	Esophagus	ESCC	3.66e-09	6.12e-01	0.1426
4296	MAP3K11	P12T-E	Human	Esophagus	ESCC	9.61e-23	4.10e-01	0.1122
4296	MAP3K11	P15T-E	Human	Esophagus	ESCC	1.93e-17	5.16e-01	0.1149
4296	MAP3K11	P16T-E	Human	Esophagus	ESCC	8.75e-22	4.45e-01	0.1153
4296	MAP3K11	P17T-E	Human	Esophagus	ESCC	1.02e-05	4.93e-01	0.1278
4296	MAP3K11	P19T-E	Human	Esophagus	ESCC	6.84e-03	5.93e-01	0.1662
4296	MAP3K11	P20T-E	Human	Esophagus	ESCC	5.10e-15	3.38e-01	0.1124
4296	MAP3K11	P21T-E	Human	Esophagus	ESCC	3.24e-35	5.87e-01	0.1617

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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:003287212	Liver	Cirrhotic	regulation of stress-activated MAPK cascade	62/4634	192/18723	1.08e-02	4.77e-02	62
GO:007099722	Liver	HCC	neuron death	202/7958	361/18723	1.44e-07	2.70e-06	202
GO:190121412	Liver	HCC	regulation of neuron death	179/7958	319/18723	5.65e-07	9.01e-06	179
GO:003109822	Liver	HCC	stress-activated protein kinase signaling cascade	138/7958	247/18723	1.43e-05	1.57e-04	138
GO:005140322	Liver	HCC	stress-activated MAPK cascade	134/7958	239/18723	1.50e-05	1.64e-04	134
GO:190121612	Liver	HCC	positive regulation of neuron death	62/7958	97/18723	1.67e-05	1.81e-04	62
GO:00448432	Liver	HCC	cell cycle G1/S phase transition	134/7958	241/18723	2.60e-05	2.70e-04	134
GO:005140212	Liver	HCC	neuron apoptotic process	135/7958	246/18723	5.64e-05	5.26e-04	135
GO:007190021	Liver	HCC	regulation of protein serine/threonine kinase activity	189/7958	359/18723	5.97e-05	5.47e-04	189
GO:004352512	Liver	HCC	positive regulation of neuron apoptotic process	39/7958	58/18723	1.22e-04	1.02e-03	39
GO:004352312	Liver	HCC	regulation of neuron apoptotic process	117/7958	212/18723	1.25e-04	1.03e-03	117
GO:00467775	Liver	HCC	protein autophosphorylation	123/7958	227/18723	2.40e-04	1.80e-03	123
GO:007030222	Liver	HCC	regulation of stress-activated protein kinase signaling cascade	105/7958	195/18723	8.79e-04	5.20e-03	105
GO:004586021	Liver	HCC	positive regulation of protein kinase activity	194/7958	386/18723	1.16e-03	6.54e-03	194
GO:003367411	Liver	HCC	positive regulation of kinase activity	230/7958	467/18723	1.72e-03	8.95e-03	230
GO:003287222	Liver	HCC	regulation of stress-activated MAPK cascade	102/7958	192/18723	1.86e-03	9.49e-03	102
GO:000725412	Liver	HCC	JNK cascade	89/7958	167/18723	3.09e-03	1.44e-02	89
GO:007099720	Oral cavity	OSCC	neuron death	202/7305	361/18723	3.75e-11	1.23e-09	202
GO:007190010	Oral cavity	OSCC	regulation of protein serine/threonine kinase activity	201/7305	359/18723	3.90e-11	1.27e-09	201
GO:003109816	Oral cavity	OSCC	stress-activated protein kinase signaling cascade	141/7305	247/18723	5.74e-09	1.25e-07	141

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0493230	Esophagus	HGIN	Non-alcoholic fatty liver disease	66/1383	155/8465	5.21e-15	1.21e-13	9.64e-14	66
hsa04932113	Esophagus	HGIN	Non-alcoholic fatty liver disease	66/1383	155/8465	5.21e-15	1.21e-13	9.64e-14	66
hsa04932210	Esophagus	ESCC	Non-alcoholic fatty liver disease	122/4205	155/8465	5.69e-14	1.59e-12	8.14e-13	122
hsa0493238	Esophagus	ESCC	Non-alcoholic fatty liver disease	122/4205	155/8465	5.69e-14	1.59e-12	8.14e-13	122
hsa0493222	Liver	Cirrhotic	Non-alcoholic fatty liver disease	106/2530	155/8465	2.16e-23	2.40e-21	1.48e-21	106
hsa0493232	Liver	Cirrhotic	Non-alcoholic fatty liver disease	106/2530	155/8465	2.16e-23	2.40e-21	1.48e-21	106
hsa0493242	Liver	HCC	Non-alcoholic fatty liver disease	124/4020	155/8465	4.54e-17	2.54e-15	1.41e-15	124
hsa0493252	Liver	HCC	Non-alcoholic fatty liver disease	124/4020	155/8465	4.54e-17	2.54e-15	1.41e-15	124
hsa0493228	Oral cavity	OSCC	Non-alcoholic fatty liver disease	124/3704	155/8465	1.22e-20	1.37e-18	6.96e-19	124
hsa0401014	Oral cavity	OSCC	MAPK signaling pathway	165/3704	302/8465	7.11e-05	2.74e-04	1.40e-04	165
hsa04932112	Oral cavity	OSCC	Non-alcoholic fatty liver disease	124/3704	155/8465	1.22e-20	1.37e-18	6.96e-19	124
hsa0401015	Oral cavity	OSCC	MAPK signaling pathway	165/3704	302/8465	7.11e-05	2.74e-04	1.40e-04	165
hsa0493229	Oral cavity	LP	Non-alcoholic fatty liver disease	101/2418	155/8465	1.53e-21	6.37e-20	4.10e-20	101
hsa0493237	Oral cavity	LP	Non-alcoholic fatty liver disease	101/2418	155/8465	1.53e-21	6.37e-20	4.10e-20	101

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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

MAP3K11

SNV

Missense_Mutation

rs760824405

c.1552N>A

p.Glu518Lys

p.E518K

Q16584

protein_coding

tolerated(0.37)

benign(0.223)

TCGA-A2-A04W-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

MAP3K11

SNV

Missense_Mutation

rs758769421

c.451G>A

p.Asp151Asn

p.D151N

Q16584

protein_coding

deleterious(0.03)

probably_damaging(0.93)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

MAP3K11

SNV

Missense_Mutation

rs779565351

c.2006N>A

p.Arg669His

p.R669H

Q16584

protein_coding

deleterious(0.04)

benign(0)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MAP3K11

deletion

Frame_Shift_Del

c.2471delN

p.Gly824AlafsTer123

p.G824Afs*123

Q16584

protein_coding

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MAP3K11

SNV

Missense_Mutation

novel

c.496N>T

p.Arg166Trp

p.R166W

Q16584

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-C5-A7X5-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

carboplatin

MAP3K11

SNV

Missense_Mutation

novel

c.553G>A

p.Glu185Lys

p.E185K

Q16584

protein_coding

tolerated(0.66)

benign(0.055)

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

MAP3K11

SNV

Missense_Mutation

novel

c.32N>A

p.Ser11Asn

p.S11N

Q16584

protein_coding

deleterious_low_confidence(0.01)

benign(0.431)

TCGA-VS-A8EC-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

carboplatin

MAP3K11

SNV

Missense_Mutation

rs756165003

c.328N>A

p.Glu110Lys

p.E110K

Q16584

protein_coding

deleterious(0.04)

benign(0.129)

TCGA-VS-A953-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MAP3K11

SNV

Missense_Mutation

rs569473618

c.2240G>A

p.Arg747His

p.R747H

Q16584

protein_coding

deleterious_low_confidence(0.05)

benign(0.374)

TCGA-A6-5661-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

MAP3K11

SNV

Missense_Mutation

c.656N>T

p.Ala219Val

p.A219V

Q16584

protein_coding

deleterious(0)

probably_damaging(0.936)

TCGA-AA-3663-01

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
4296	MAP3K11	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME	inhibitor	249565853	CEP-1347
4296	MAP3K11	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME	inhibitor	CHEMBL290352	CEP-1347
4296	MAP3K11	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME	inhibitor	249565875
4296	MAP3K11	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME	inhibitor	249565786
4296	MAP3K11	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME		CEP-1347	CEP-1347	24044867

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