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: CD109

Gene summary for CD109

Gene summary.

Gene information	Species	Human
	Gene symbol	CD109
	Gene ID	135228
	Gene name	CD109 molecule
	Gene Alias	CPAMD7
	Cytomap	6q13
	Gene Type	protein-coding
	GO ID	GO:0000768
	UniProtAcc	Q6YHK3

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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
135228	CD109	CA_HPV_2	Human	Cervix	CC	8.22e-04	2.97e-01	0.0391
135228	CD109	CCI_1	Human	Cervix	CC	3.11e-12	1.47e+00	0.528
135228	CD109	Tumor	Human	Cervix	CC	2.04e-02	2.21e-01	0.1241
135228	CD109	sample3	Human	Cervix	CC	2.49e-03	2.62e-01	0.1387
135228	CD109	H2	Human	Cervix	HSIL_HPV	4.09e-05	-1.66e-01	0.0632
135228	CD109	T3	Human	Cervix	CC	4.56e-07	2.35e-01	0.1389
135228	CD109	LZE2T	Human	Esophagus	ESCC	1.40e-02	3.36e-01	0.082
135228	CD109	LZE4T	Human	Esophagus	ESCC	1.57e-16	3.99e-01	0.0811
135228	CD109	LZE24T	Human	Esophagus	ESCC	3.88e-04	-4.32e-02	0.0596
135228	CD109	LZE6T	Human	Esophagus	ESCC	5.42e-03	-3.94e-02	0.0845
135228	CD109	P2T-E	Human	Esophagus	ESCC	7.05e-13	2.04e-01	0.1177
135228	CD109	P4T-E	Human	Esophagus	ESCC	1.90e-17	6.25e-01	0.1323
135228	CD109	P5T-E	Human	Esophagus	ESCC	4.03e-26	5.18e-01	0.1327
135228	CD109	P8T-E	Human	Esophagus	ESCC	5.98e-06	1.85e-01	0.0889
135228	CD109	P9T-E	Human	Esophagus	ESCC	2.47e-09	2.68e-01	0.1131
135228	CD109	P10T-E	Human	Esophagus	ESCC	2.54e-16	3.07e-01	0.116
135228	CD109	P11T-E	Human	Esophagus	ESCC	1.85e-06	6.39e-01	0.1426
135228	CD109	P12T-E	Human	Esophagus	ESCC	2.55e-22	5.43e-01	0.1122
135228	CD109	P15T-E	Human	Esophagus	ESCC	2.39e-17	6.11e-01	0.1149
135228	CD109	P16T-E	Human	Esophagus	ESCC	1.46e-04	3.26e-04	0.1153

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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:005134622	Liver	HCC	negative regulation of hydrolase activity	195/7958	379/18723	2.44e-04	1.82e-03	195
GO:000717921	Liver	HCC	transforming growth factor beta receptor signaling pathway	106/7958	198/18723	1.09e-03	6.23e-03	106
GO:19038442	Liver	HCC	regulation of cellular response to transforming growth factor beta stimulus	72/7958	131/18723	2.65e-03	1.27e-02	72
GO:001095121	Liver	HCC	negative regulation of endopeptidase activity	129/7958	252/18723	3.17e-03	1.47e-02	129
GO:001701511	Liver	HCC	regulation of transforming growth factor beta receptor signaling pathway	70/7958	128/18723	3.56e-03	1.59e-02	70
GO:001046621	Liver	HCC	negative regulation of peptidase activity	132/7958	262/18723	5.82e-03	2.42e-02	132
GO:004206020	Oral cavity	OSCC	wound healing	237/7305	422/18723	4.51e-13	2.18e-11	237
GO:005254720	Oral cavity	OSCC	regulation of peptidase activity	255/7305	461/18723	5.78e-13	2.75e-11	255
GO:001056320	Oral cavity	OSCC	negative regulation of phosphorus metabolic process	246/7305	442/18723	6.12e-13	2.89e-11	246
GO:004593620	Oral cavity	OSCC	negative regulation of phosphate metabolic process	245/7305	441/18723	8.85e-13	4.09e-11	245
GO:003009920	Oral cavity	OSCC	myeloid cell differentiation	213/7305	381/18723	1.24e-11	4.42e-10	213
GO:004232619	Oral cavity	OSCC	negative regulation of phosphorylation	214/7305	385/18723	2.30e-11	7.74e-10	214
GO:005254820	Oral cavity	OSCC	regulation of endopeptidase activity	235/7305	432/18723	4.35e-11	1.40e-09	235
GO:000193319	Oral cavity	OSCC	negative regulation of protein phosphorylation	191/7305	342/18723	1.58e-10	4.62e-09	191
GO:000257310	Oral cavity	OSCC	myeloid leukocyte differentiation	119/7305	208/18723	7.29e-08	1.29e-06	119
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:00435887	Oral cavity	OSCC	skin development	143/7305	263/18723	2.77e-07	4.27e-06	143
GO:00085449	Oral cavity	OSCC	epidermis development	171/7305	324/18723	2.89e-07	4.43e-06	171
GO:004586120	Oral cavity	OSCC	negative regulation of proteolysis	181/7305	351/18723	1.01e-06	1.37e-05	181

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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

CD109

SNV

Missense_Mutation

rs137899447

c.445N>T

p.Arg149Cys

p.R149C

Q6YHK3

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

CD109

SNV

Missense_Mutation

c.3391C>G

p.Leu1131Val

p.L1131V

Q6YHK3

protein_coding

deleterious(0.01)

benign(0.062)

TCGA-A8-A07W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

exemestane

CD109

SNV

Missense_Mutation

rs745425108

c.917C>T

p.Ser306Leu

p.S306L

Q6YHK3

protein_coding

tolerated(0.16)

benign(0.013)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CD109

SNV

Missense_Mutation

c.2918C>G

p.Ser973Cys

p.S973C

Q6YHK3

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CD109

SNV

Missense_Mutation

c.3850G>C

p.Asp1284His

p.D1284H

Q6YHK3

protein_coding

deleterious(0.02)

possibly_damaging(0.813)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CD109

SNV

Missense_Mutation

rs137899447

c.445C>T

p.Arg149Cys

p.R149C

Q6YHK3

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CD109

SNV

Missense_Mutation

rs776870550

c.627A>T

p.Gln209His

p.Q209H

Q6YHK3

protein_coding

deleterious(0.02)

possibly_damaging(0.722)

TCGA-AN-A0FL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CD109

SNV

Missense_Mutation

novel

c.2636C>T

p.Thr879Ile

p.T879I

Q6YHK3

protein_coding

tolerated(0.09)

benign(0.101)

TCGA-BH-A0HB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

CD109

SNV

Missense_Mutation

c.1090N>G

p.Leu364Val

p.L364V

Q6YHK3

protein_coding

deleterious(0)

probably_damaging(0.927)

TCGA-C8-A12P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CD109

SNV

Missense_Mutation

rs202157387

c.79N>T

p.Arg27Trp

p.R27W

Q6YHK3

protein_coding

deleterious(0.01)

possibly_damaging(0.727)

TCGA-E2-A2P5-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

arimidex

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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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