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: LTBP2

Gene summary for LTBP2

Gene summary.

Gene information	Species	Human
	Gene symbol	LTBP2
	Gene ID	4053
	Gene name	latent transforming growth factor beta binding protein 2
	Gene Alias	C14orf141
	Cytomap	14q24.3
	Gene Type	protein-coding
	GO ID	GO:0006605
	UniProtAcc	Q14767

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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
4053	LTBP2	P8T-E	Human	Esophagus	ESCC	2.99e-08	1.38e-01	0.0889
4053	LTBP2	P12T-E	Human	Esophagus	ESCC	1.07e-04	-4.07e-02	0.1122
4053	LTBP2	P15T-E	Human	Esophagus	ESCC	6.46e-06	4.83e-02	0.1149
4053	LTBP2	P21T-E	Human	Esophagus	ESCC	5.39e-04	5.08e-02	0.1617
4053	LTBP2	P24T-E	Human	Esophagus	ESCC	2.14e-03	9.88e-02	0.1287
4053	LTBP2	P26T-E	Human	Esophagus	ESCC	1.38e-10	-7.24e-03	0.1276
4053	LTBP2	P27T-E	Human	Esophagus	ESCC	3.55e-07	1.51e-01	0.1055
4053	LTBP2	P36T-E	Human	Esophagus	ESCC	1.11e-02	2.13e-01	0.1187
4053	LTBP2	P37T-E	Human	Esophagus	ESCC	7.66e-18	4.22e-01	0.1371
4053	LTBP2	P42T-E	Human	Esophagus	ESCC	5.05e-03	2.49e-01	0.1175
4053	LTBP2	P47T-E	Human	Esophagus	ESCC	4.85e-02	1.85e-02	0.1067
4053	LTBP2	P48T-E	Human	Esophagus	ESCC	1.96e-02	3.30e-03	0.0959
4053	LTBP2	P52T-E	Human	Esophagus	ESCC	3.59e-04	1.01e-01	0.1555
4053	LTBP2	P61T-E	Human	Esophagus	ESCC	5.00e-04	6.31e-02	0.099
4053	LTBP2	P62T-E	Human	Esophagus	ESCC	5.75e-10	2.71e-01	0.1302
4053	LTBP2	P65T-E	Human	Esophagus	ESCC	3.09e-10	1.58e-01	0.0978
4053	LTBP2	P76T-E	Human	Esophagus	ESCC	5.45e-05	5.94e-02	0.1207
4053	LTBP2	P79T-E	Human	Esophagus	ESCC	5.61e-10	2.75e-01	0.1154
4053	LTBP2	P83T-E	Human	Esophagus	ESCC	3.13e-07	1.37e-01	0.1738
4053	LTBP2	P89T-E	Human	Esophagus	ESCC	6.29e-04	5.85e-01	0.1752

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0006605111	Esophagus	ESCC	protein targeting	229/8552	314/18723	4.93e-23	1.01e-20	229
GO:00715599	Esophagus	ESCC	response to transforming growth factor beta	157/8552	256/18723	2.95e-07	4.23e-06	157
GO:00715609	Esophagus	ESCC	cellular response to transforming growth factor beta stimulus	151/8552	250/18723	1.78e-06	2.10e-05	151
GO:00071799	Esophagus	ESCC	transforming growth factor beta receptor signaling pathway	121/8552	198/18723	8.26e-06	8.03e-05	121
GO:000717810	Esophagus	ESCC	transmembrane receptor protein serine/threonine kinase signaling pathway	195/8552	355/18723	2.58e-04	1.58e-03	195
GO:000930617	Esophagus	ESCC	protein secretion	190/8552	359/18723	3.22e-03	1.34e-02	190
GO:003559217	Esophagus	ESCC	establishment of protein localization to extracellular region	190/8552	360/18723	3.77e-03	1.53e-02	190
GO:007169210	Esophagus	ESCC	protein localization to extracellular region	193/8552	368/18723	5.01e-03	1.92e-02	193
GO:000660520	Oral cavity	OSCC	protein targeting	204/7305	314/18723	6.78e-21	1.13e-18	204
GO:00715598	Oral cavity	OSCC	response to transforming growth factor beta	140/7305	256/18723	2.34e-07	3.70e-06	140
GO:00715608	Oral cavity	OSCC	cellular response to transforming growth factor beta stimulus	137/7305	250/18723	2.68e-07	4.15e-06	137
GO:00071798	Oral cavity	OSCC	transforming growth factor beta receptor signaling pathway	109/7305	198/18723	3.21e-06	3.86e-05	109
GO:000930610	Oral cavity	OSCC	protein secretion	169/7305	359/18723	1.04e-03	5.34e-03	169
GO:003559210	Oral cavity	OSCC	establishment of protein localization to extracellular region	169/7305	360/18723	1.21e-03	6.08e-03	169
GO:00716929	Oral cavity	OSCC	protein localization to extracellular region	172/7305	368/18723	1.40e-03	6.79e-03	172
GO:00071789	Oral cavity	OSCC	transmembrane receptor protein serine/threonine kinase signaling pathway	165/7305	355/18723	2.31e-03	1.02e-02	165
GO:000660518	Prostate	BPH	protein targeting	102/3107	314/18723	2.51e-12	2.05e-10	102
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:00071797	Prostate	BPH	transforming growth factor beta receptor signaling pathway	57/3107	198/18723	1.17e-05	1.58e-04	57

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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

LTBP2

SNV

Missense_Mutation

rs778443565

c.4160G>A

p.Arg1387His

p.R1387H

Q14767

protein_coding

tolerated(0.06)

benign(0.009)

TCGA-A2-A0CT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

LTBP2

SNV

Missense_Mutation

rs144907368

c.2714N>A

p.Arg905His

p.R905H

Q14767

protein_coding

tolerated(0.15)

possibly_damaging(0.839)

TCGA-A2-A3KD-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

LTBP2

SNV

Missense_Mutation

novel

c.4382A>G

p.Glu1461Gly

p.E1461G

Q14767

protein_coding

deleterious(0)

possibly_damaging(0.727)

TCGA-A8-A09A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

LTBP2

SNV

Missense_Mutation

c.2606N>C

p.Arg869Thr

p.R869T

Q14767

protein_coding

tolerated(1)

benign(0.003)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

LTBP2

SNV

Missense_Mutation

c.1265N>T

p.Ser422Phe

p.S422F

Q14767

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

LTBP2

SNV

Missense_Mutation

rs137854858

c.1484N>A

p.Arg495Gln

p.R495Q

Q14767

protein_coding

tolerated(0.37)

possibly_damaging(0.849)

TCGA-BH-A0BR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

LTBP2

SNV

Missense_Mutation

c.2105N>A

p.Gly702Asp

p.G702D

Q14767

protein_coding

deleterious(0)

possibly_damaging(0.885)

TCGA-D8-A1XG-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

LTBP2

SNV

Missense_Mutation

c.3664N>C

p.Cys1222Arg

p.C1222R

Q14767

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

LTBP2

SNV

Missense_Mutation

novel

c.3204N>A

p.Asn1068Lys

p.N1068K

Q14767

protein_coding

deleterious(0)

possibly_damaging(0.735)

TCGA-PL-A8LZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

LTBP2

insertion

In_Frame_Ins

novel

c.751_752insGCCTGTGCTCTGGATTTCTCTACAGCC

p.Ala251delinsGlyLeuCysSerGlyPheLeuTyrSerPro

p.A251delinsGLCSGFLYSP

Q14767

protein_coding

TCGA-B6-A0I8-01

Breast

breast invasive 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

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