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: FKBP8

Gene summary for FKBP8

Gene summary.

Gene information	Species	Human
	Gene symbol	FKBP8
	Gene ID	23770
	Gene name	FKBP prolyl isomerase 8
	Gene Alias	FKBP38
	Cytomap	19p13.11
	Gene Type	protein-coding
	GO ID	GO:0000413
	UniProtAcc	A0A024R7P2

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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
23770	FKBP8	GSM4909280	Human	Breast	Precancer	4.16e-02	-4.46e-01	0.0305
23770	FKBP8	GSM4909285	Human	Breast	IDC	4.53e-08	3.32e-01	0.21
23770	FKBP8	GSM4909294	Human	Breast	IDC	6.51e-06	-1.68e-01	0.2022
23770	FKBP8	GSM4909296	Human	Breast	IDC	1.37e-10	-3.12e-01	0.1524
23770	FKBP8	GSM4909297	Human	Breast	IDC	7.53e-16	-2.96e-01	0.1517
23770	FKBP8	GSM4909301	Human	Breast	IDC	6.05e-03	-1.41e-01	0.1577
23770	FKBP8	GSM4909309	Human	Breast	IDC	8.27e-04	-2.31e-01	0.0483
23770	FKBP8	GSM4909311	Human	Breast	IDC	3.32e-34	-2.39e-01	0.1534
23770	FKBP8	GSM4909312	Human	Breast	IDC	2.59e-15	8.29e-02	0.1552
23770	FKBP8	GSM4909316	Human	Breast	IDC	2.74e-05	1.38e-02	0.21
23770	FKBP8	GSM4909319	Human	Breast	IDC	1.44e-52	-9.80e-02	0.1563
23770	FKBP8	GSM4909320	Human	Breast	IDC	2.06e-13	2.96e-01	0.1575
23770	FKBP8	GSM4909321	Human	Breast	IDC	4.75e-56	7.64e-01	0.1559
23770	FKBP8	NCCBC14	Human	Breast	DCIS	3.36e-10	-1.73e-01	0.2021
23770	FKBP8	NCCBC2	Human	Breast	DCIS	1.57e-06	-2.67e-01	0.1554
23770	FKBP8	NCCBC3	Human	Breast	DCIS	3.82e-02	-1.02e-02	0.1198
23770	FKBP8	NCCBC5	Human	Breast	DCIS	7.19e-15	1.08e-02	0.2046
23770	FKBP8	P1	Human	Breast	IDC	2.95e-19	-2.44e-01	0.1527
23770	FKBP8	P2	Human	Breast	IDC	1.59e-02	-6.85e-02	0.21
23770	FKBP8	DCIS2	Human	Breast	DCIS	1.24e-50	4.56e-02	0.0085

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:00064578	Breast	Precancer	protein folding	43/1080	212/18723	3.48e-13	7.45e-11	43
GO:00182085	Breast	Precancer	peptidyl-proline modification	10/1080	58/18723	1.62e-03	1.65e-02	10
GO:000645713	Breast	IDC	protein folding	47/1434	212/18723	2.31e-11	3.86e-09	47
GO:001820812	Breast	IDC	peptidyl-proline modification	13/1434	58/18723	3.59e-04	5.18e-03	13
GO:00459369	Breast	IDC	negative regulation of phosphate metabolic process	53/1434	441/18723	7.21e-04	8.79e-03	53
GO:00105639	Breast	IDC	negative regulation of phosphorus metabolic process	53/1434	442/18723	7.60e-04	9.25e-03	53
GO:000645723	Breast	DCIS	protein folding	47/1390	212/18723	7.84e-12	1.53e-09	47
GO:001820821	Breast	DCIS	peptidyl-proline modification	13/1390	58/18723	2.65e-04	4.03e-03	13
GO:004593614	Breast	DCIS	negative regulation of phosphate metabolic process	53/1390	441/18723	3.48e-04	4.96e-03	53
GO:001056314	Breast	DCIS	negative regulation of phosphorus metabolic process	53/1390	442/18723	3.68e-04	5.18e-03	53
GO:00423269	Breast	DCIS	negative regulation of phosphorylation	43/1390	385/18723	4.78e-03	3.62e-02	43
GO:00019339	Breast	DCIS	negative regulation of protein phosphorylation	39/1390	342/18723	4.94e-03	3.71e-02	39
GO:000645710	Endometrium	AEH	protein folding	61/2100	212/18723	1.86e-12	3.48e-10	61
GO:00071787	Endometrium	AEH	transmembrane receptor protein serine/threonine kinase signaling pathway	67/2100	355/18723	1.28e-05	2.80e-04	67
GO:004593616	Endometrium	AEH	negative regulation of phosphate metabolic process	77/2100	441/18723	5.13e-05	8.25e-04	77
GO:001056316	Endometrium	AEH	negative regulation of phosphorus metabolic process	77/2100	442/18723	5.54e-05	8.79e-04	77
GO:000193315	Endometrium	AEH	negative regulation of protein phosphorylation	60/2100	342/18723	2.89e-04	3.31e-03	60
GO:00305092	Endometrium	AEH	BMP signaling pathway	32/2100	152/18723	3.15e-04	3.54e-03	32
GO:00004133	Endometrium	AEH	protein peptidyl-prolyl isomerization	13/2100	42/18723	4.74e-04	4.91e-03	13
GO:00182086	Endometrium	AEH	peptidyl-proline modification	16/2100	58/18723	4.75e-04	4.91e-03	16

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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

FKBP8

SNV

Missense_Mutation

c.928N>G

p.Leu310Val

p.L310V

Q14318

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-A8-A08L-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

FKBP8

SNV

Missense_Mutation

c.747N>G

p.Ile249Met

p.I249M

Q14318

protein_coding

deleterious(0.01)

possibly_damaging(0.753)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FKBP8

SNV

Missense_Mutation

rs760604410

c.454N>A

p.Val152Ile

p.V152I

Q14318

protein_coding

deleterious(0.05)

possibly_damaging(0.719)

TCGA-AQ-A0Y5-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

FKBP8

SNV

Missense_Mutation

novel

c.136G>C

p.Glu46Gln

p.E46Q

Q14318

protein_coding

tolerated_low_confidence(0.07)

benign(0.01)

TCGA-B6-A0RG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

FKBP8

SNV

Missense_Mutation

novel

c.127N>C

p.Glu43Gln

p.E43Q

Q14318

protein_coding

deleterious_low_confidence(0.04)

benign(0.025)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

FKBP8

SNV

Missense_Mutation

c.451N>T

p.Asp151Tyr

p.D151Y

Q14318

protein_coding

deleterious(0)

probably_damaging(0.971)

TCGA-D8-A1XO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

FKBP8

insertion

Nonsense_Mutation

novel

c.491_492insAAAAATTTAAAAATTAGCTGGGTGTGGGCCGGG

p.Asp164delinsGluLysIleTerLysLeuAlaGlyCysGlyProGly

p.D164delinsEKI*KLAGCGPG

Q14318

protein_coding

TCGA-B6-A0RG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

FKBP8

insertion

Frame_Shift_Ins

novel

c.77_78insTTTATTTTTTGTAGAGATGGGGTCTC

p.Asp28PhefsTer31

p.D28Ffs*31

Q14318

protein_coding

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

FKBP8

SNV

Missense_Mutation

c.1105C>A

p.Leu369Met

p.L369M

Q14318

protein_coding

deleterious(0.03)

possibly_damaging(0.725)

TCGA-C5-A1BL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

FKBP8

SNV

Missense_Mutation

rs771523688

c.1064C>T

p.Ala355Val

p.A355V

Q14318

protein_coding

tolerated(0.08)

benign(0.02)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

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

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