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: PIM3

Gene summary for PIM3

Gene summary.

Gene information	Species	Human
	Gene symbol	PIM3
	Gene ID	415116
	Gene name	Pim-3 proto-oncogene, serine/threonine kinase
	Gene Alias	pim-3
	Cytomap	22q13.33
	Gene Type	protein-coding
	GO ID	GO:0000278
	UniProtAcc	Q86V86

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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
415116	PIM3	HTA11_696_2000001011	Human	Colorectum	AD	3.39e-04	2.99e-01	-0.1464
415116	PIM3	HTA11_1391_2000001011	Human	Colorectum	AD	1.18e-03	4.05e-01	-0.059
415116	PIM3	HTA11_866_3004761011	Human	Colorectum	AD	8.65e-13	4.78e-01	0.096
415116	PIM3	HTA11_7696_3000711011	Human	Colorectum	AD	1.76e-04	4.11e-01	0.0674
415116	PIM3	HTA11_99999970781_79442	Human	Colorectum	MSS	1.75e-15	6.31e-01	0.294
415116	PIM3	HTA11_99999965104_69814	Human	Colorectum	MSS	1.52e-03	2.26e-01	0.281
415116	PIM3	HTA11_99999971662_82457	Human	Colorectum	MSS	1.01e-13	6.29e-01	0.3859
415116	PIM3	HTA11_99999973899_84307	Human	Colorectum	MSS	3.70e-07	8.29e-01	0.2585
415116	PIM3	HTA11_99999974143_84620	Human	Colorectum	MSS	3.31e-06	3.42e-01	0.3005
415116	PIM3	A001-C-108	Human	Colorectum	FAP	3.24e-02	-2.07e-01	-0.0272
415116	PIM3	A002-C-205	Human	Colorectum	FAP	1.02e-03	-2.11e-01	-0.1236
415116	PIM3	A015-C-104	Human	Colorectum	FAP	6.74e-03	-5.22e-02	-0.1899
415116	PIM3	A002-C-116	Human	Colorectum	FAP	2.83e-04	-2.27e-01	-0.0452
415116	PIM3	F034	Human	Colorectum	FAP	1.20e-05	-2.30e-01	-0.0665
415116	PIM3	AEH-subject1	Human	Endometrium	AEH	2.66e-06	2.59e-01	-0.3059
415116	PIM3	EEC-subject2	Human	Endometrium	EEC	3.65e-03	1.85e-01	-0.2607
415116	PIM3	EEC-subject3	Human	Endometrium	EEC	1.14e-07	1.60e-01	-0.2525
415116	PIM3	EEC-subject4	Human	Endometrium	EEC	1.22e-05	2.88e-01	-0.2571
415116	PIM3	GSM5276934	Human	Endometrium	EEC	5.77e-06	3.58e-01	-0.0913
415116	PIM3	GSM5276937	Human	Endometrium	EEC	2.03e-22	7.18e-01	-0.0897

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
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:0009743	Colorectum	AD	response to carbohydrate	86/3918	253/18723	8.43e-07	2.90e-05	86
GO:0034284	Colorectum	AD	response to monosaccharide	76/3918	225/18723	4.64e-06	1.23e-04	76
GO:0033500	Colorectum	AD	carbohydrate homeostasis	84/3918	259/18723	9.10e-06	2.15e-04	84
GO:0009746	Colorectum	AD	response to hexose	73/3918	219/18723	1.20e-05	2.65e-04	73
GO:0009749	Colorectum	AD	response to glucose	71/3918	212/18723	1.31e-05	2.85e-04	71
GO:0042593	Colorectum	AD	glucose homeostasis	83/3918	258/18723	1.44e-05	3.11e-04	83
GO:0001678	Colorectum	AD	cellular glucose homeostasis	60/3918	172/18723	1.49e-05	3.18e-04	60
GO:0046777	Colorectum	AD	protein autophosphorylation	74/3918	227/18723	2.48e-05	4.76e-04	74
GO:0071322	Colorectum	AD	cellular response to carbohydrate stimulus	56/3918	163/18723	4.61e-05	7.97e-04	56
GO:0050708	Colorectum	AD	regulation of protein secretion	83/3918	268/18723	6.59e-05	1.07e-03	83
GO:0071333	Colorectum	AD	cellular response to glucose stimulus	52/3918	151/18723	7.88e-05	1.25e-03	52
GO:0009306	Colorectum	AD	protein secretion	105/3918	359/18723	1.05e-04	1.57e-03	105
GO:0071331	Colorectum	AD	cellular response to hexose stimulus	52/3918	153/18723	1.16e-04	1.71e-03	52
GO:0035592	Colorectum	AD	establishment of protein localization to extracellular region	105/3918	360/18723	1.18e-04	1.73e-03	105
GO:0071326	Colorectum	AD	cellular response to monosaccharide stimulus	52/3918	154/18723	1.40e-04	1.98e-03	52
GO:0071692	Colorectum	AD	protein localization to extracellular region	106/3918	368/18723	1.86e-04	2.49e-03	106
GO:0050796	Colorectum	AD	regulation of insulin secretion	54/3918	165/18723	2.60e-04	3.25e-03	54
GO:0030073	Colorectum	AD	insulin secretion	61/3918	195/18723	4.28e-04	4.81e-03	61
GO:0061178	Colorectum	AD	regulation of insulin secretion involved in cellular response to glucose stimulus	25/3918	64/18723	6.98e-04	7.10e-03	25
GO:0015833	Colorectum	AD	peptide transport	77/3918	264/18723	8.90e-04	8.60e-03	77

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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

PIM3

SNV

Missense_Mutation

c.913N>A

p.Asp305Asn

p.D305N

Q86V86

protein_coding

tolerated_low_confidence(0.18)

benign(0.015)

TCGA-AR-A0TX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PIM3

SNV

Missense_Mutation

rs750652937

c.674C>T

p.Ser225Leu

p.S225L

Q86V86

protein_coding

deleterious(0.04)

benign(0.217)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PIM3

SNV

Missense_Mutation

novel

c.856N>A

p.Gln286Lys

p.Q286K

Q86V86

protein_coding

deleterious(0.04)

possibly_damaging(0.506)

TCGA-C5-A8YR-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PIM3

SNV

Missense_Mutation

c.671G>A

p.Arg224His

p.R224H

Q86V86

protein_coding

tolerated(0.14)

possibly_damaging(0.891)

TCGA-G4-6309-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

xeloda

PIM3

SNV

Missense_Mutation

rs775149860

c.542N>A

p.Arg181His

p.R181H

Q86V86

protein_coding

deleterious(0.03)

benign(0.117)

TCGA-F5-6810-01

Colorectum

rectum adenocarcinoma

Unknown

I/II

Unknown

PIM3

SNV

Missense_Mutation

novel

c.482N>A

p.Cys161Tyr

p.C161Y

Q86V86

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A5-A0G1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PIM3

SNV

Missense_Mutation

novel

c.793N>A

p.Glu265Lys

p.E265K

Q86V86

protein_coding

deleterious(0.02)

benign(0.391)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PIM3

SNV

Missense_Mutation

novel

c.909C>A

p.Ser303Arg

p.S303R

Q86V86

protein_coding

tolerated_low_confidence(0.24)

benign(0.168)

TCGA-AJ-A2QO-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PIM3

SNV

Missense_Mutation

novel

c.667G>A

p.Gly223Arg

p.G223R

Q86V86

protein_coding

deleterious(0)

probably_damaging(0.982)

TCGA-AX-A2HD-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

PIM3

SNV

Missense_Mutation

c.645N>T

p.Trp215Cys

p.W215C

Q86V86

protein_coding

deleterious(0)

probably_damaging(0.933)

TCGA-D1-A103-01

Endometrium

uterine corpus endometrioid carcinoma

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
415116	PIM3	KINASE, DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE		VADIMEZAN	VADIMEZAN
415116	PIM3	KINASE, DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE		SOTRASTAURIN	SOTRASTAURIN
415116	PIM3	KINASE, DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE		US9580418, Example 11
415116	PIM3	KINASE, DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE	inhibitor	223366031
415116	PIM3	KINASE, DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE		LY-2090314	LY-2090314
415116	PIM3	KINASE, DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE		US8987457, 198
415116	PIM3	KINASE, DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE		BDBM50061612
415116	PIM3	KINASE, DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE	inhibitor	328083469
415116	PIM3	KINASE, DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE		US8481586, 15
415116	PIM3	KINASE, DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE		GEFITINIB	GEFITINIB

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