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: MAPK9

Gene summary for MAPK9

Gene summary.

Gene information	Species	Human
	Gene symbol	MAPK9
	Gene ID	5601
	Gene name	mitogen-activated protein kinase 9
	Gene Alias	JNK-55
	Cytomap	5q35.3
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	P45984

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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
5601	MAPK9	HCC1_Meng	Human	Liver	HCC	8.68e-34	7.52e-02	0.0246
5601	MAPK9	HCC2_Meng	Human	Liver	HCC	3.98e-17	1.46e-01	0.0107
5601	MAPK9	HCC1	Human	Liver	HCC	6.43e-04	3.66e+00	0.5336
5601	MAPK9	HCC2	Human	Liver	HCC	4.10e-08	3.09e+00	0.5341
5601	MAPK9	S028	Human	Liver	HCC	3.27e-10	3.28e-01	0.2503
5601	MAPK9	S029	Human	Liver	HCC	2.46e-13	5.40e-01	0.2581
5601	MAPK9	C04	Human	Oral cavity	OSCC	1.35e-03	4.51e-01	0.2633
5601	MAPK9	C21	Human	Oral cavity	OSCC	2.97e-02	2.50e-01	0.2678
5601	MAPK9	C30	Human	Oral cavity	OSCC	7.37e-11	6.10e-01	0.3055
5601	MAPK9	C43	Human	Oral cavity	OSCC	2.05e-07	1.94e-01	0.1704
5601	MAPK9	C46	Human	Oral cavity	OSCC	1.55e-02	2.00e-01	0.1673
5601	MAPK9	C51	Human	Oral cavity	OSCC	1.91e-02	2.88e-01	0.2674
5601	MAPK9	C08	Human	Oral cavity	OSCC	1.87e-13	2.94e-01	0.1919
5601	MAPK9	LN38	Human	Oral cavity	OSCC	2.56e-02	6.71e-01	0.168
5601	MAPK9	SYSMH2	Human	Oral cavity	OSCC	8.65e-07	2.77e-01	0.2326
5601	MAPK9	SYSMH3	Human	Oral cavity	OSCC	1.24e-10	1.71e-01	0.2442
5601	MAPK9	SYSMH6	Human	Oral cavity	OSCC	4.24e-02	1.05e-01	0.1275
5601	MAPK9	male-WTA	Human	Thyroid	PTC	2.32e-22	1.83e-01	0.1037
5601	MAPK9	PTC01	Human	Thyroid	PTC	1.13e-04	1.51e-02	0.1899
5601	MAPK9	PTC04	Human	Thyroid	PTC	1.89e-13	1.69e-01	0.1927

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:190305221	Liver	HCC	positive regulation of proteolysis involved in cellular protein catabolic process	96/7958	133/18723	3.47e-12	1.57e-10	96
GO:000030222	Liver	HCC	response to reactive oxygen species	144/7958	222/18723	1.24e-11	5.09e-10	144
GO:190180012	Liver	HCC	positive regulation of proteasomal protein catabolic process	84/7958	114/18723	1.28e-11	5.21e-10	84
GO:003133412	Liver	HCC	positive regulation of protein-containing complex assembly	150/7958	237/18723	7.35e-11	2.63e-09	150
GO:19033221	Liver	HCC	positive regulation of protein modification by small protein conjugation or removal	94/7958	138/18723	9.87e-10	3.01e-08	94
GO:200006022	Liver	HCC	positive regulation of ubiquitin-dependent protein catabolic process	76/7958	107/18723	2.06e-09	5.79e-08	76
GO:003243612	Liver	HCC	positive regulation of proteasomal ubiquitin-dependent protein catabolic process	66/7958	90/18723	2.79e-09	7.55e-08	66
GO:003461412	Liver	HCC	cellular response to reactive oxygen species	102/7958	155/18723	3.70e-09	9.89e-08	102
GO:00313981	Liver	HCC	positive regulation of protein ubiquitination	79/7958	119/18723	1.18e-07	2.26e-06	79
GO:001003822	Liver	HCC	response to metal ion	208/7958	373/18723	1.35e-07	2.56e-06	208
GO:19021151	Liver	HCC	regulation of organelle assembly	110/7958	186/18723	3.30e-06	4.34e-05	110
GO:200123522	Liver	HCC	positive regulation of apoptotic signaling pathway	79/7958	126/18723	3.70e-06	4.82e-05	79
GO:000756822	Liver	HCC	aging	185/7958	339/18723	4.28e-06	5.50e-05	185
GO:004668622	Liver	HCC	response to cadmium ion	47/7958	68/18723	8.13e-06	9.56e-05	47
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:001810511	Liver	HCC	peptidyl-serine phosphorylation	169/7958	315/18723	3.86e-05	3.81e-04	169
GO:000762321	Liver	HCC	circadian rhythm	117/7958	210/18723	7.29e-05	6.54e-04	117
GO:001820911	Liver	HCC	peptidyl-serine modification	177/7958	338/18723	1.45e-04	1.17e-03	177
GO:004851121	Liver	HCC	rhythmic process	156/7958	298/18723	3.54e-04	2.46e-03	156

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414122	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0501222	Liver	HCC	Parkinson disease	198/4020	266/8465	9.40e-20	1.58e-17	8.76e-18	198
hsa0501622	Liver	HCC	Huntington disease	219/4020	306/8465	3.06e-18	3.42e-16	1.90e-16	219
hsa0520842	Liver	HCC	Chemical carcinogenesis - reactive oxygen species	167/4020	223/8465	2.85e-17	1.91e-15	1.06e-15	167
hsa0493242	Liver	HCC	Non-alcoholic fatty liver disease	124/4020	155/8465	4.54e-17	2.54e-15	1.41e-15	124
hsa0502022	Liver	HCC	Prion disease	195/4020	273/8465	3.26e-16	1.56e-14	8.67e-15	195
hsa0541522	Liver	HCC	Diabetic cardiomyopathy	151/4020	203/8465	2.72e-15	1.01e-13	5.63e-14	151
hsa0513242	Liver	HCC	Salmonella infection	178/4020	249/8465	5.90e-15	1.98e-13	1.10e-13	178
hsa0517142	Liver	HCC	Coronavirus disease - COVID-19	167/4020	232/8465	1.50e-14	4.19e-13	2.33e-13	167
hsa0501022	Liver	HCC	Alzheimer disease	254/4020	384/8465	3.75e-14	8.97e-13	4.99e-13	254
hsa0502222	Liver	HCC	Pathways of neurodegeneration - multiple diseases	298/4020	476/8465	6.59e-12	1.30e-10	7.22e-11	298
hsa0414021	Liver	HCC	Autophagy - animal	99/4020	141/8465	3.08e-08	4.70e-07	2.61e-07	99
hsa0521022	Liver	HCC	Colorectal cancer	65/4020	86/8465	8.85e-08	1.23e-06	6.87e-07	65
hsa0491041	Liver	HCC	Insulin signaling pathway	95/4020	137/8465	1.53e-07	1.97e-06	1.10e-06	95
hsa0513042	Liver	HCC	Pathogenic Escherichia coli infection	129/4020	197/8465	2.02e-07	2.50e-06	1.39e-06	129
hsa0493121	Liver	HCC	Insulin resistance	77/4020	108/8465	3.89e-07	4.46e-06	2.48e-06	77
hsa0513542	Liver	HCC	Yersinia infection	92/4020	137/8465	2.25e-06	2.19e-05	1.22e-05	92
hsa0453042	Liver	HCC	Tight junction	110/4020	169/8465	2.45e-06	2.28e-05	1.27e-05	110
hsa0516921	Liver	HCC	Epstein-Barr virus infection	128/4020	202/8465	3.17e-06	2.79e-05	1.55e-05	128
hsa0516622	Liver	HCC	Human T-cell leukemia virus 1 infection	139/4020	222/8465	3.17e-06	2.79e-05	1.55e-05	139

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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

MAPK9

SNV

Missense_Mutation

novel

c.523A>T

p.Thr175Ser

p.T175S

P45984

protein_coding

tolerated(0.5)

benign(0.001)

TCGA-AN-A0FL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MAPK9

insertion

In_Frame_Ins

novel

c.944_945insATCTATTCTGTGCCATTGGCTTTGGTTACATCC

p.Ala315_Leu316insSerIleLeuCysHisTrpLeuTrpLeuHisPro

p.A315_L316insSILCHWLWLHP

P45984

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MAPK9

insertion

In_Frame_Ins

novel

c.521_522insTGTTCACAGGCACTTCTTGTTTCTGGTTTTTTGTTT

p.Arg174_Thr175insValHisArgHisPheLeuPheLeuValPheCysLeu

p.R174_T175insVHRHFLFLVFCL

P45984

protein_coding

TCGA-AN-A0FL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MAPK9

SNV

Missense_Mutation

c.196N>T

p.His66Tyr

p.H66Y

P45984

protein_coding

deleterious(0.02)

possibly_damaging(0.672)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MAPK9

SNV

Missense_Mutation

c.877N>G

p.Gln293Glu

p.Q293E

P45984

protein_coding

tolerated(0.22)

benign(0.103)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MAPK9

SNV

Missense_Mutation

c.373N>T

p.His125Tyr

p.H125Y

P45984

protein_coding

deleterious(0)

probably_damaging(0.983)

TCGA-UC-A7PF-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MAPK9

SNV

Missense_Mutation

novel

c.1190C>T

p.Ser397Leu

p.S397L

P45984

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.879)

TCGA-VS-A94Z-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MAPK9

SNV

Missense_Mutation

novel

c.715G>A

p.Glu239Lys

p.E239K

P45984

protein_coding

tolerated(0.33)

benign(0.152)

TCGA-AA-3930-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Chemotherapy

capecitabine

MAPK9

SNV

Missense_Mutation

novel

c.752N>C

p.Lys251Thr

p.K251T

P45984

protein_coding

deleterious(0)

possibly_damaging(0.897)

TCGA-AA-3984-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

MAPK9

SNV

Missense_Mutation

c.1078G>C

p.Val360Leu

p.V360L

P45984

protein_coding

deleterious(0.04)

benign(0.011)

TCGA-AA-A02F-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Chemotherapy

folinic

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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
5601	MAPK9	KINASE, SERINE THREONINE KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, ENZYME		CAMPTOTHECIN	CAMPTOTHECIN	10839298
5601	MAPK9	KINASE, SERINE THREONINE KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, ENZYME		PMID25991433-Compound-P4
5601	MAPK9	KINASE, SERINE THREONINE KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, ENZYME	inhibitor	178102618
5601	MAPK9	KINASE, SERINE THREONINE KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, ENZYME		AG-1879	CHEMBL406845
5601	MAPK9	KINASE, SERINE THREONINE KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, ENZYME		OSI-632	OSI-632
5601	MAPK9	KINASE, SERINE THREONINE KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, ENZYME	inhibitor	178101956
5601	MAPK9	KINASE, SERINE THREONINE KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, ENZYME		PD-0166285	PD-0166285
5601	MAPK9	KINASE, SERINE THREONINE KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, ENZYME		SB-220025	SB-220025
5601	MAPK9	KINASE, SERINE THREONINE KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, ENZYME		PMID25991433-Compound-O3
5601	MAPK9	KINASE, SERINE THREONINE KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, ENZYME	inhibitor	223366077	RGB-286638

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