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: MAP3K14

Gene summary for MAP3K14

Gene summary.

Gene information	Species	Human
	Gene symbol	MAP3K14
	Gene ID	9020
	Gene name	mitogen-activated protein kinase kinase kinase 14
	Gene Alias	FTDCR1B
	Cytomap	17q21.31
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	Q68D39

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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
9020	MAP3K14	RNA-P17T-P17T-2	Human	Lung	IAC	6.84e-03	5.27e-01	0.3371
9020	MAP3K14	RNA-P17T-P17T-4	Human	Lung	IAC	5.14e-05	5.12e-01	0.343
9020	MAP3K14	RNA-P17T-P17T-6	Human	Lung	IAC	1.97e-06	6.67e-01	0.3385
9020	MAP3K14	RNA-P6T2-P6T2-1	Human	Lung	IAC	2.45e-04	3.44e-01	-0.0166
9020	MAP3K14	RNA-P6T2-P6T2-2	Human	Lung	IAC	2.25e-05	3.39e-01	-0.0132
9020	MAP3K14	RNA-P6T2-P6T2-3	Human	Lung	IAC	6.18e-09	4.10e-01	-0.013
9020	MAP3K14	RNA-P6T2-P6T2-4	Human	Lung	IAC	8.37e-03	2.85e-01	-0.0121
9020	MAP3K14	C30	Human	Oral cavity	OSCC	1.14e-12	5.51e-01	0.3055
9020	MAP3K14	C46	Human	Oral cavity	OSCC	1.04e-10	4.00e-01	0.1673
9020	MAP3K14	LN46	Human	Oral cavity	OSCC	9.60e-13	5.01e-01	0.1666
9020	MAP3K14	EOLP-1	Human	Oral cavity	EOLP	9.19e-03	1.55e-01	-0.0202
9020	MAP3K14	SYSMH2	Human	Oral cavity	OSCC	1.41e-04	2.58e-01	0.2326
9020	MAP3K14	SYSMH3	Human	Oral cavity	OSCC	1.49e-03	1.73e-01	0.2442

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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

∗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:00072495	Lung	IAC	I-kappaB kinase/NF-kappaB signaling	56/2061	281/18723	7.39e-06	2.62e-04	56
GO:00431226	Lung	IAC	regulation of I-kappaB kinase/NF-kappaB signaling	51/2061	249/18723	8.41e-06	2.87e-04	51
GO:00714968	Lung	IAC	cellular response to external stimulus	60/2061	320/18723	2.50e-05	6.76e-04	60
GO:00431235	Lung	IAC	positive regulation of I-kappaB kinase/NF-kappaB signaling	38/2061	186/18723	1.19e-04	2.25e-03	38
GO:00712146	Lung	IAC	cellular response to abiotic stimulus	58/2061	331/18723	2.30e-04	3.96e-03	58
GO:01040046	Lung	IAC	cellular response to environmental stimulus	58/2061	331/18723	2.30e-04	3.96e-03	58
GO:00096156	Lung	IAC	response to virus	61/2061	367/18723	6.75e-04	9.12e-03	61
GO:00096125	Lung	IAC	response to mechanical stimulus	39/2061	216/18723	1.29e-03	1.45e-02	39
GO:000961515	Oral cavity	OSCC	response to virus	215/7305	367/18723	1.63e-14	9.41e-13	215
GO:004312218	Oral cavity	OSCC	regulation of I-kappaB kinase/NF-kappaB signaling	155/7305	249/18723	7.79e-14	4.14e-12	155
GO:004312310	Oral cavity	OSCC	positive regulation of I-kappaB kinase/NF-kappaB signaling	122/7305	186/18723	1.68e-13	8.52e-12	122
GO:000724910	Oral cavity	OSCC	I-kappaB kinase/NF-kappaB signaling	169/7305	281/18723	4.69e-13	2.25e-11	169
GO:007149620	Oral cavity	OSCC	cellular response to external stimulus	186/7305	320/18723	2.56e-12	1.05e-10	186
GO:007121416	Oral cavity	OSCC	cellular response to abiotic stimulus	186/7305	331/18723	1.38e-10	4.10e-09	186
GO:010400416	Oral cavity	OSCC	cellular response to environmental stimulus	186/7305	331/18723	1.38e-10	4.10e-09	186
GO:00516074	Oral cavity	OSCC	defense response to virus	154/7305	265/18723	1.96e-10	5.63e-09	154
GO:01405464	Oral cavity	OSCC	defense response to symbiont	154/7305	265/18723	1.96e-10	5.63e-09	154
GO:00712605	Oral cavity	OSCC	cellular response to mechanical stimulus	52/7305	81/18723	3.86e-06	4.55e-05	52
GO:000961210	Oral cavity	OSCC	response to mechanical stimulus	115/7305	216/18723	1.43e-05	1.44e-04	115
GO:00380614	Oral cavity	OSCC	NIK/NF-kappaB signaling	78/7305	143/18723	1.14e-04	8.35e-04	78

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0520816	Lung	IAC	Chemical carcinogenesis - reactive oxygen species	51/1053	223/8465	8.45e-06	2.14e-04	1.42e-04	51
hsa0516616	Lung	IAC	Human T-cell leukemia virus 1 infection	49/1053	222/8465	3.44e-05	6.38e-04	4.24e-04	49
hsa040108	Lung	IAC	MAPK signaling pathway	62/1053	302/8465	3.54e-05	6.38e-04	4.24e-04	62
hsa051205	Lung	IAC	Epithelial cell signaling in Helicobacter pylori infection	20/1053	70/8465	2.31e-04	2.54e-03	1.68e-03	20
hsa04625	Lung	IAC	C-type lectin receptor signaling pathway	26/1053	104/8465	3.15e-04	3.11e-03	2.06e-03	26
hsa042107	Lung	IAC	Apoptosis	30/1053	136/8465	1.11e-03	7.82e-03	5.19e-03	30
hsa0516916	Lung	IAC	Epstein-Barr virus infection	40/1053	202/8465	1.72e-03	9.66e-03	6.41e-03	40
hsa046685	Lung	IAC	TNF signaling pathway	25/1053	114/8465	3.01e-03	1.53e-02	1.02e-02	25
hsa04380	Lung	IAC	Osteoclast differentiation	27/1053	128/8465	3.74e-03	1.84e-02	1.22e-02	27
hsa04660	Lung	IAC	T cell receptor signaling pathway	23/1053	104/8465	3.88e-03	1.88e-02	1.25e-02	23
hsa049364	Lung	IAC	Alcoholic liver disease	29/1053	142/8465	4.45e-03	2.07e-02	1.37e-02	29
hsa0520817	Lung	IAC	Chemical carcinogenesis - reactive oxygen species	51/1053	223/8465	8.45e-06	2.14e-04	1.42e-04	51
hsa0516617	Lung	IAC	Human T-cell leukemia virus 1 infection	49/1053	222/8465	3.44e-05	6.38e-04	4.24e-04	49
hsa0401011	Lung	IAC	MAPK signaling pathway	62/1053	302/8465	3.54e-05	6.38e-04	4.24e-04	62
hsa0512012	Lung	IAC	Epithelial cell signaling in Helicobacter pylori infection	20/1053	70/8465	2.31e-04	2.54e-03	1.68e-03	20
hsa046251	Lung	IAC	C-type lectin receptor signaling pathway	26/1053	104/8465	3.15e-04	3.11e-03	2.06e-03	26
hsa0421012	Lung	IAC	Apoptosis	30/1053	136/8465	1.11e-03	7.82e-03	5.19e-03	30
hsa0516917	Lung	IAC	Epstein-Barr virus infection	40/1053	202/8465	1.72e-03	9.66e-03	6.41e-03	40
hsa0466812	Lung	IAC	TNF signaling pathway	25/1053	114/8465	3.01e-03	1.53e-02	1.02e-02	25
hsa043801	Lung	IAC	Osteoclast differentiation	27/1053	128/8465	3.74e-03	1.84e-02	1.22e-02	27

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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

MAP3K14

SNV

Missense_Mutation

novel

c.1223N>C

p.Arg408Thr

p.R408T

Q99558

protein_coding

tolerated(0.55)

benign(0.248)

TCGA-BH-A0B7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

MAP3K14

SNV

Missense_Mutation

novel

c.250G>T

p.Ala84Ser

p.A84S

Q99558

protein_coding

deleterious(0.01)

probably_damaging(0.991)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

MAP3K14

SNV

Missense_Mutation

rs762235528

c.2275N>G

p.Pro759Ala

p.P759A

Q99558

protein_coding

tolerated(0.87)

benign(0)

TCGA-E2-A14S-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

MAP3K14

SNV

Missense_Mutation

novel

c.793N>T

p.His265Tyr

p.H265Y

Q99558

protein_coding

tolerated_low_confidence(0.89)

benign(0.255)

TCGA-C5-A3HE-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MAP3K14

SNV

Missense_Mutation

novel

c.1630G>C

p.Asp544His

p.D544H

Q99558

protein_coding

deleterious(0.02)

benign(0.074)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MAP3K14

SNV

Missense_Mutation

novel

c.127G>C

p.Glu43Gln

p.E43Q

Q99558

protein_coding

deleterious_low_confidence(0.02)

probably_damaging(0.994)

TCGA-MA-AA41-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MAP3K14

SNV

Missense_Mutation

novel

c.1223N>C

p.Arg408Thr

p.R408T

Q99558

protein_coding

tolerated(0.55)

benign(0.248)

TCGA-Q1-A73P-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MAP3K14

SNV

Missense_Mutation

rs558318157

c.559N>A

p.Ala187Thr

p.A187T

Q99558

protein_coding

tolerated(1)

benign(0)

TCGA-VS-A94Z-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MAP3K14

SNV

Missense_Mutation

novel

c.742N>A

p.Gly248Arg

p.G248R

Q99558

protein_coding

tolerated_low_confidence(0.36)

benign(0)

TCGA-A6-2679-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

MAP3K14

SNV

Missense_Mutation

novel

c.1724C>T

p.Ala575Val

p.A575V

Q99558

protein_coding

tolerated(0.24)

benign(0.185)

TCGA-A6-5661-01

Colorectum

colon adenocarcinoma

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
9020	MAP3K14	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE	inhibitor	374883851
9020	MAP3K14	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE	inhibitor	374883852
9020	MAP3K14	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE	inhibitor	249565854
9020	MAP3K14	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE	inhibitor	405560388

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