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: LDLRAD4

Gene summary for LDLRAD4

Gene summary.

Gene information	Species	Human
	Gene symbol	LDLRAD4
	Gene ID	753
	Gene name	low density lipoprotein receptor class A domain containing 4
	Gene Alias	C18orf1
	Cytomap	18p11.21
	Gene Type	protein-coding
	GO ID	GO:0001837
	UniProtAcc	O15165

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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
753	LDLRAD4	GSM4909286	Human	Breast	IDC	8.53e-05	1.41e-01	0.1081
753	LDLRAD4	GSM4909290	Human	Breast	IDC	1.16e-10	3.74e-01	0.2096
753	LDLRAD4	GSM4909304	Human	Breast	IDC	1.87e-19	5.27e-01	0.1636
753	LDLRAD4	GSM4909305	Human	Breast	IDC	3.42e-10	4.17e-01	0.0436
753	LDLRAD4	GSM4909306	Human	Breast	IDC	2.54e-14	3.42e-01	0.1564
753	LDLRAD4	GSM4909307	Human	Breast	IDC	5.42e-24	5.97e-01	0.1569
753	LDLRAD4	GSM4909308	Human	Breast	IDC	1.31e-31	6.05e-01	0.158
753	LDLRAD4	GSM4909317	Human	Breast	IDC	1.14e-05	3.01e-01	0.1355
753	LDLRAD4	GSM4909320	Human	Breast	IDC	1.76e-05	5.98e-01	0.1575
753	LDLRAD4	P3	Human	Breast	IDC	5.87e-05	6.35e-01	0.1542
753	LDLRAD4	DCIS2	Human	Breast	DCIS	5.14e-56	2.35e-01	0.0085
753	LDLRAD4	HTA11_3410_2000001011	Human	Colorectum	AD	5.29e-27	-6.95e-01	0.0155
753	LDLRAD4	HTA11_2487_2000001011	Human	Colorectum	SER	1.57e-18	-8.60e-01	-0.1808
753	LDLRAD4	HTA11_78_2000001011	Human	Colorectum	AD	8.83e-05	-5.43e-01	-0.1088
753	LDLRAD4	HTA11_411_2000001011	Human	Colorectum	SER	7.88e-07	-9.18e-01	-0.2602
753	LDLRAD4	HTA11_2112_2000001011	Human	Colorectum	SER	7.04e-11	-9.75e-01	-0.2196
753	LDLRAD4	HTA11_3361_2000001011	Human	Colorectum	AD	3.12e-11	-6.76e-01	-0.1207
753	LDLRAD4	HTA11_83_2000001011	Human	Colorectum	SER	7.95e-08	-4.87e-01	-0.1526
753	LDLRAD4	HTA11_696_2000001011	Human	Colorectum	AD	1.16e-05	-1.74e-01	-0.1464
753	LDLRAD4	HTA11_2992_2000001011	Human	Colorectum	SER	1.75e-02	-7.07e-01	-0.1706

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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
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
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma

∗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:004001312	Endometrium	EEC	negative regulation of locomotion	74/2168	391/18723	1.28e-05	2.59e-04	74
GO:007156014	Endometrium	EEC	cellular response to transforming growth factor beta stimulus	52/2168	250/18723	1.81e-05	3.41e-04	52
GO:000717814	Endometrium	EEC	transmembrane receptor protein serine/threonine kinase signaling pathway	68/2168	355/18723	1.90e-05	3.50e-04	68
GO:003133315	Endometrium	EEC	negative regulation of protein-containing complex assembly	32/2168	141/18723	1.32e-04	1.73e-03	32
GO:004876212	Endometrium	EEC	mesenchymal cell differentiation	47/2168	236/18723	1.35e-04	1.76e-03	47
GO:004593617	Endometrium	EEC	negative regulation of phosphate metabolic process	77/2168	441/18723	1.45e-04	1.87e-03	77
GO:001056317	Endometrium	EEC	negative regulation of phosphorus metabolic process	77/2168	442/18723	1.56e-04	1.97e-03	77
GO:006048512	Endometrium	EEC	mesenchyme development	54/2168	291/18723	3.01e-04	3.37e-03	54
GO:000183712	Endometrium	EEC	epithelial to mesenchymal transition	33/2168	157/18723	4.71e-04	4.84e-03	33
GO:000717914	Endometrium	EEC	transforming growth factor beta receptor signaling pathway	39/2168	198/18723	6.03e-04	5.98e-03	39
GO:000193316	Endometrium	EEC	negative regulation of protein phosphorylation	59/2168	342/18723	1.11e-03	9.48e-03	59
GO:004232616	Endometrium	EEC	negative regulation of phosphorylation	65/2168	385/18723	1.13e-03	9.67e-03	65
GO:009009211	Endometrium	EEC	regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	44/2168	256/18723	4.72e-03	3.00e-02	44
GO:00715593	Liver	NAFLD	response to transforming growth factor beta	51/1882	256/18723	1.43e-06	6.58e-05	51
GO:00423267	Liver	NAFLD	negative regulation of phosphorylation	67/1882	385/18723	5.49e-06	1.98e-04	67
GO:00715603	Liver	NAFLD	cellular response to transforming growth factor beta stimulus	48/1882	250/18723	8.27e-06	2.76e-04	48
GO:00459367	Liver	NAFLD	negative regulation of phosphate metabolic process	73/1882	441/18723	1.31e-05	3.93e-04	73
GO:00105637	Liver	NAFLD	negative regulation of phosphorus metabolic process	73/1882	442/18723	1.42e-05	4.17e-04	73
GO:00071793	Liver	NAFLD	transforming growth factor beta receptor signaling pathway	37/1882	198/18723	1.53e-04	2.82e-03	37
GO:00432547	Liver	NAFLD	regulation of protein-containing complex assembly	66/1882	428/18723	2.83e-04	4.53e-03	66

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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

LDLRAD4

SNV

Missense_Mutation

c.99C>A

p.Asn33Lys

p.N33K

O15165

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.451)

TCGA-D8-A1JS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

LDLRAD4

SNV

Missense_Mutation

c.643N>A

p.Asp215Asn

p.D215N

O15165

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

LDLRAD4

SNV

Missense_Mutation

novel

c.161N>T

p.Pro54Leu

p.P54L

O15165

protein_coding

deleterious(0.03)

probably_damaging(0.998)

TCGA-5M-AAT6-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Unknown

LDLRAD4

SNV

Missense_Mutation

c.791N>A

p.Gly264Asp

p.G264D

O15165

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.965)

TCGA-AA-3672-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

LDLRAD4

SNV

Missense_Mutation

c.665C>T

p.Ala222Val

p.A222V

O15165

protein_coding

tolerated_low_confidence(0.06)

benign(0.021)

TCGA-D5-6930-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

LDLRAD4

SNV

Missense_Mutation

c.493N>A

p.Glu165Lys

p.E165K

O15165

protein_coding

tolerated(0.05)

benign(0.306)

TCGA-EI-6917-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

5fluorouracil+oxaciplatina+l-folinian

LDLRAD4

SNV

Missense_Mutation

novel

c.833G>A

p.Gly278Asp

p.G278D

O15165

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-A5-A2K5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

LDLRAD4

SNV

Missense_Mutation

novel

c.329N>C

p.Leu110Pro

p.L110P

O15165

protein_coding

deleterious(0.04)

benign(0.037)

TCGA-AJ-A8CT-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

LDLRAD4

SNV

Missense_Mutation

c.619N>A

p.Ala207Thr

p.A207T

O15165

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

LDLRAD4

SNV

Missense_Mutation

novel

c.280C>T

p.Arg94Trp

p.R94W

O15165

protein_coding

tolerated(0.16)

benign(0.006)

TCGA-AP-A1DK-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

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