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: LTBP1

Gene summary for LTBP1

Gene summary.

Gene information	Species	Human
	Gene symbol	LTBP1
	Gene ID	4052
	Gene name	latent transforming growth factor beta binding protein 1
	Gene Alias	ARCL2E
	Cytomap	2p22.3
	Gene Type	protein-coding
	GO ID	GO:0001816
	UniProtAcc	Q14766

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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
4052	LTBP1	AEH-subject1	Human	Endometrium	AEH	9.53e-03	1.83e-01	-0.3059
4052	LTBP1	AEH-subject2	Human	Endometrium	AEH	8.73e-03	2.21e-01	-0.2525
4052	LTBP1	AEH-subject3	Human	Endometrium	AEH	5.17e-03	1.56e-01	-0.2576
4052	LTBP1	AEH-subject4	Human	Endometrium	AEH	1.54e-08	3.56e-01	-0.2657
4052	LTBP1	AEH-subject5	Human	Endometrium	AEH	7.23e-06	2.69e-01	-0.2953
4052	LTBP1	EEC-subject1	Human	Endometrium	EEC	1.26e-23	6.94e-01	-0.2682
4052	LTBP1	EEC-subject2	Human	Endometrium	EEC	2.45e-03	2.16e-01	-0.2607
4052	LTBP1	EEC-subject3	Human	Endometrium	EEC	4.85e-14	1.50e-01	-0.2525
4052	LTBP1	EEC-subject4	Human	Endometrium	EEC	5.33e-25	7.17e-01	-0.2571
4052	LTBP1	EEC-subject5	Human	Endometrium	EEC	1.60e-15	6.05e-01	-0.249
4052	LTBP1	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	1.35e-14	-7.35e-02	-0.1869
4052	LTBP1	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	4.13e-17	-6.60e-02	-0.1875
4052	LTBP1	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	7.29e-21	-1.60e-01	-0.1883
4052	LTBP1	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	5.09e-15	1.66e-02	-0.1934
4052	LTBP1	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	1.40e-23	-1.87e-01	-0.1917
4052	LTBP1	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	1.94e-17	-2.27e-01	-0.1916
4052	LTBP1	GSM6177623_NYU_UCEC3_Vis	Human	Endometrium	EEC	9.73e-04	-1.36e-01	-0.1269
4052	LTBP1	LZE24T	Human	Esophagus	ESCC	2.65e-02	3.83e-02	0.0596
4052	LTBP1	LZE6T	Human	Esophagus	ESCC	9.86e-05	6.72e-01	0.0845
4052	LTBP1	P1T-E	Human	Esophagus	ESCC	5.31e-04	1.30e-01	0.0875

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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:000717923	Oral cavity	NEOLP	transforming growth factor beta receptor signaling pathway	48/2005	198/18723	4.01e-08	1.66e-06	48
GO:000717822	Oral cavity	NEOLP	transmembrane receptor protein serine/threonine kinase signaling pathway	70/2005	355/18723	3.04e-07	9.62e-06	70
GO:001701521	Oral cavity	NEOLP	regulation of transforming growth factor beta receptor signaling pathway	33/2005	128/18723	1.18e-06	3.08e-05	33
GO:190384421	Oral cavity	NEOLP	regulation of cellular response to transforming growth factor beta stimulus	33/2005	131/18723	2.05e-06	4.86e-05	33
GO:003051211	Oral cavity	NEOLP	negative regulation of transforming growth factor beta receptor signaling pathway	24/2005	81/18723	2.40e-06	5.53e-05	24
GO:005123531	Oral cavity	NEOLP	maintenance of location	62/2005	327/18723	5.41e-06	1.12e-04	62
GO:00901011	Oral cavity	NEOLP	negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	32/2005	131/18723	5.88e-06	1.19e-04	32
GO:004518531	Oral cavity	NEOLP	maintenance of protein location	25/2005	94/18723	1.25e-05	2.25e-04	25
GO:009028711	Oral cavity	NEOLP	regulation of cellular response to growth factor stimulus	56/2005	304/18723	3.55e-05	5.20e-04	56
GO:009009213	Oral cavity	NEOLP	regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	49/2005	256/18723	3.90e-05	5.62e-04	49
GO:007163431	Oral cavity	NEOLP	regulation of transforming growth factor beta production	14/2005	41/18723	5.34e-05	7.29e-04	14
GO:007160431	Oral cavity	NEOLP	transforming growth factor beta production	14/2005	43/18723	9.66e-05	1.18e-03	14
GO:00715597	Prostate	BPH	response to transforming growth factor beta	76/3107	256/18723	1.14e-07	2.73e-06	76
GO:00715607	Prostate	BPH	cellular response to transforming growth factor beta stimulus	72/3107	250/18723	8.71e-07	1.61e-05	72
GO:004518518	Prostate	BPH	maintenance of protein location	35/3107	94/18723	1.16e-06	2.07e-05	35
GO:00071797	Prostate	BPH	transforming growth factor beta receptor signaling pathway	57/3107	198/18723	1.17e-05	1.58e-04	57
GO:00071788	Prostate	BPH	transmembrane receptor protein serine/threonine kinase signaling pathway	90/3107	355/18723	1.48e-05	1.90e-04	90
GO:005123516	Prostate	BPH	maintenance of location	80/3107	327/18723	1.55e-04	1.36e-03	80
GO:00716345	Prostate	BPH	regulation of transforming growth factor beta production	16/3107	41/18723	5.01e-04	3.57e-03	16
GO:19038445	Prostate	BPH	regulation of cellular response to transforming growth factor beta stimulus	37/3107	131/18723	5.57e-04	3.89e-03	37

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa043504	Endometrium	AEH	TGF-beta signaling pathway	26/1197	108/8465	3.82e-03	2.18e-02	1.59e-02	26
hsa0435011	Endometrium	AEH	TGF-beta signaling pathway	26/1197	108/8465	3.82e-03	2.18e-02	1.59e-02	26
hsa043502	Endometrium	EEC	TGF-beta signaling pathway	26/1237	108/8465	5.95e-03	3.12e-02	2.33e-02	26
hsa043503	Endometrium	EEC	TGF-beta signaling pathway	26/1237	108/8465	5.95e-03	3.12e-02	2.33e-02	26
hsa043507	Esophagus	ESCC	TGF-beta signaling pathway	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa0435014	Esophagus	ESCC	TGF-beta signaling pathway	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa043506	Oral cavity	OSCC	TGF-beta signaling pathway	60/3704	108/8465	8.66e-03	1.97e-02	1.00e-02	60
hsa0435013	Oral cavity	OSCC	TGF-beta signaling pathway	60/3704	108/8465	8.66e-03	1.97e-02	1.00e-02	60
hsa0435041	Oral cavity	NEOLP	TGF-beta signaling pathway	28/1112	108/8465	2.46e-04	1.62e-03	1.02e-03	28
hsa0435051	Oral cavity	NEOLP	TGF-beta signaling pathway	28/1112	108/8465	2.46e-04	1.62e-03	1.02e-03	28
hsa043505	Prostate	BPH	TGF-beta signaling pathway	35/1718	108/8465	1.98e-03	7.92e-03	4.90e-03	35
hsa0435012	Prostate	BPH	TGF-beta signaling pathway	35/1718	108/8465	1.98e-03	7.92e-03	4.90e-03	35
hsa0435021	Prostate	Tumor	TGF-beta signaling pathway	39/1791	108/8465	2.33e-04	1.35e-03	8.39e-04	39
hsa0435031	Prostate	Tumor	TGF-beta signaling pathway	39/1791	108/8465	2.33e-04	1.35e-03	8.39e-04	39

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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

LTBP1

SNV

Missense_Mutation

novel

c.4960G>C

p.Asp1654His

p.D1654H

Q14766

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

LTBP1

SNV

Missense_Mutation

c.2086N>T

p.His696Tyr

p.H696Y

Q14766

protein_coding

deleterious(0.01)

benign(0.366)

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

LTBP1

SNV

Missense_Mutation

c.4876N>C

p.Gly1626Arg

p.G1626R

Q14766

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A8-A076-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

LTBP1

SNV

Missense_Mutation

c.3138N>G

p.Asn1046Lys

p.N1046K

Q14766

protein_coding

tolerated(0.88)

benign(0.003)

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

LTBP1

SNV

Missense_Mutation

novel

c.2511N>T

p.Gln837His

p.Q837H

Q14766

protein_coding

deleterious(0.02)

benign(0.025)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

LTBP1

SNV

Missense_Mutation

c.2878G>C

p.Glu960Gln

p.E960Q

Q14766

protein_coding

deleterious(0.02)

probably_damaging(0.959)

TCGA-AN-A0XW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

LTBP1

SNV

Missense_Mutation

c.3898G>A

p.Ala1300Thr

p.A1300T

Q14766

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

LTBP1

SNV

Missense_Mutation

rs748096563

c.3959A>G

p.Tyr1320Cys

p.Y1320C

Q14766

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-B6-A0RE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

LTBP1

SNV

Missense_Mutation

c.3705N>G

p.Ile1235Met

p.I1235M

Q14766

protein_coding

tolerated(0.2)

possibly_damaging(0.689)

TCGA-BH-A0BO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

LTBP1

SNV

Missense_Mutation

c.2983N>G

p.Arg995Gly

p.R995G

Q14766

protein_coding

deleterious(0.04)

benign(0.062)

TCGA-BH-A0DL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

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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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