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: MERTK

Gene summary for MERTK

Gene summary.

Gene information	Species	Human
	Gene symbol	MERTK
	Gene ID	10461
	Gene name	MER proto-oncogene, tyrosine kinase
	Gene Alias	MER
	Cytomap	2q13
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q12866

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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
10461	MERTK	EEC-subject1	Human	Endometrium	EEC	2.82e-03	2.11e-01	-0.2682

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Endometrium		AEH: Atypical endometrial hyperplasia
Endometrium		EEC: Endometrioid 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:003158915	Endometrium	EEC	cell-substrate adhesion	87/2168	363/18723	1.95e-11	3.00e-09	87
GO:004206017	Endometrium	EEC	wound healing	92/2168	422/18723	1.12e-09	9.58e-08	92
GO:006145815	Endometrium	EEC	reproductive system development	91/2168	427/18723	4.54e-09	3.13e-07	91
GO:004860814	Endometrium	EEC	reproductive structure development	90/2168	424/18723	6.77e-09	4.41e-07	90
GO:003444615	Endometrium	EEC	substrate adhesion-dependent cell spreading	33/2168	108/18723	9.56e-08	4.69e-06	33
GO:003367415	Endometrium	EEC	positive regulation of kinase activity	83/2168	467/18723	4.32e-05	7.10e-04	83
GO:004887217	Endometrium	EEC	homeostasis of number of cells	53/2168	272/18723	9.52e-05	1.34e-03	53
GO:000226217	Endometrium	EEC	myeloid cell homeostasis	35/2168	157/18723	9.62e-05	1.35e-03	35
GO:000759613	Endometrium	EEC	blood coagulation	44/2168	217/18723	1.42e-04	1.84e-03	44
GO:000759913	Endometrium	EEC	hemostasis	44/2168	222/18723	2.43e-04	2.85e-03	44
GO:005081713	Endometrium	EEC	coagulation	44/2168	222/18723	2.43e-04	2.85e-03	44
GO:00466601	Endometrium	EEC	female sex differentiation	26/2168	114/18723	4.99e-04	5.05e-03	26
GO:005087816	Endometrium	EEC	regulation of body fluid levels	65/2168	379/18723	7.48e-04	7.05e-03	65
GO:000268313	Endometrium	EEC	negative regulation of immune system process	72/2168	434/18723	1.04e-03	9.13e-03	72
GO:00075481	Endometrium	EEC	sex differentiation	48/2168	276/18723	2.58e-03	1.87e-02	48
GO:003016811	Endometrium	EEC	platelet activation	25/2168	123/18723	3.47e-03	2.35e-02	25
GO:004349113	Endometrium	EEC	protein kinase B signaling	38/2168	211/18723	3.74e-03	2.49e-02	38

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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
GAS6	MERTK	GAS6_MERTK	GAS	Breast	DCIS
GAS6	MERTK	GAS6_MERTK	GAS	Cervix	CC
GAS6	MERTK	GAS6_MERTK	GAS	CRC	AD
GAS6	MERTK	GAS6_MERTK	GAS	CRC	ADJ
GAS6	MERTK	GAS6_MERTK	GAS	CRC	CRC
GAS6	MERTK	GAS6_MERTK	GAS	CRC	MSI-H
GAS6	MERTK	GAS6_MERTK	GAS	CRC	SER
GAS6	MERTK	GAS6_MERTK	GAS	Endometrium	ADJ
GAS6	MERTK	GAS6_MERTK	GAS	Endometrium	Healthy
GAS6	MERTK	GAS6_MERTK	GAS	HNSCC	OSCC
GAS6	MERTK	GAS6_MERTK	GAS	Liver	HCC
GAS6	MERTK	GAS6_MERTK	GAS	Liver	Healthy
GAS6	MERTK	GAS6_MERTK	GAS	Liver	Precancer
GAS6	MERTK	GAS6_MERTK	GAS	Lung	AIS
GAS6	MERTK	GAS6_MERTK	GAS	Lung	IAC
GAS6	MERTK	GAS6_MERTK	GAS	Lung	MIAC
GAS6	MERTK	GAS6_MERTK	GAS	Lung	Precancer
GAS6	MERTK	GAS6_MERTK	GAS	Prostate	ADJ
GAS6	MERTK	GAS6_MERTK	GAS	Prostate	BPH
GAS6	MERTK	GAS6_MERTK	GAS	Prostate	Tumor

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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

MERTK

SNV

Missense_Mutation

rs770809648

c.592N>T

p.His198Tyr

p.H198Y

Q12866

protein_coding

tolerated(0.7)

benign(0.001)

TCGA-A2-A3Y0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

MERTK

SNV

Missense_Mutation

c.2431N>C

p.Asp811His

p.D811H

Q12866

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MERTK

SNV

Missense_Mutation

rs868703580

c.718N>A

p.Glu240Lys

p.E240K

Q12866

protein_coding

tolerated(0.26)

benign(0.003)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MERTK

SNV

Missense_Mutation

c.2550N>C

p.Leu850Phe

p.L850F

Q12866

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

MERTK

SNV

Missense_Mutation

rs766215580

c.865N>A

p.Glu289Lys

p.E289K

Q12866

protein_coding

tolerated(0.27)

benign(0.003)

TCGA-D8-A147-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

MERTK

SNV

Missense_Mutation

c.547N>A

p.Glu183Lys

p.E183K

Q12866

protein_coding

tolerated(0.2)

possibly_damaging(0.903)

TCGA-D8-A1J9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MERTK

SNV

Missense_Mutation

c.1252N>T

p.Val418Leu

p.V418L

Q12866

protein_coding

tolerated(1)

benign(0)

TCGA-E9-A1N8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

MERTK

deletion

Frame_Shift_Del

c.2049_2067delNNNNNNNNNNNNNNNNNNN

p.Leu684GlnfsTer12

p.L684Qfs*12

Q12866

protein_coding

TCGA-A2-A0SW-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

arimidex

MERTK

deletion

Frame_Shift_Del

novel

c.145delN

p.Pro49ArgfsTer15

p.P49Rfs*15

Q12866

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

MERTK

SNV

Missense_Mutation

novel

c.1240G>A

p.Asp414Asn

p.D414N

Q12866

protein_coding

tolerated(1)

benign(0)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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
10461	MERTK	KINASE, TYROSINE KINASE, ENZYME, CLINICALLY ACTIONABLE, DRUGGABLE GENOME	inhibitor	381118841
10461	MERTK	KINASE, TYROSINE KINASE, ENZYME, CLINICALLY ACTIONABLE, DRUGGABLE GENOME	inhibitor	381118865
10461	MERTK	KINASE, TYROSINE KINASE, ENZYME, CLINICALLY ACTIONABLE, DRUGGABLE GENOME	inhibitor	249565788
10461	MERTK	KINASE, TYROSINE KINASE, ENZYME, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		UNC1062		23585477
10461	MERTK	KINASE, TYROSINE KINASE, ENZYME, CLINICALLY ACTIONABLE, DRUGGABLE GENOME	inhibitor	363894135	MERESTINIB
10461	MERTK	KINASE, TYROSINE KINASE, ENZYME, CLINICALLY ACTIONABLE, DRUGGABLE GENOME	inhibitor	252827366	GILTERITINIB
10461	MERTK	KINASE, TYROSINE KINASE, ENZYME, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		ONO-7475
10461	MERTK	KINASE, TYROSINE KINASE, ENZYME, CLINICALLY ACTIONABLE, DRUGGABLE GENOME	inhibitor	249565645	MK-2461
10461	MERTK	KINASE, TYROSINE KINASE, ENZYME, CLINICALLY ACTIONABLE, DRUGGABLE GENOME	inhibitor	HESPERADIN	HESPERADIN	19035792
10461	MERTK	KINASE, TYROSINE KINASE, ENZYME, CLINICALLY ACTIONABLE, DRUGGABLE GENOME	inhibitor	385612233

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