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: CDC73

Gene summary for CDC73

Gene summary.

Gene information	Species	Human
	Gene symbol	CDC73
	Gene ID	79577
	Gene name	cell division cycle 73
	Gene Alias	C1orf28
	Cytomap	1q31.2
	Gene Type	protein-coding
	GO ID	GO:0000082
	UniProtAcc	Q6P1J9

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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
79577	CDC73	LZE4T	Human	Esophagus	ESCC	3.76e-18	5.13e-01	0.0811
79577	CDC73	LZE5T	Human	Esophagus	ESCC	1.74e-06	2.06e-01	0.0514
79577	CDC73	LZE7T	Human	Esophagus	ESCC	1.18e-06	6.35e-01	0.0667
79577	CDC73	LZE8T	Human	Esophagus	ESCC	3.93e-05	9.85e-02	0.067
79577	CDC73	LZE20T	Human	Esophagus	ESCC	1.80e-12	2.40e-01	0.0662
79577	CDC73	LZE22D1	Human	Esophagus	HGIN	1.62e-04	9.87e-02	0.0595
79577	CDC73	LZE22T	Human	Esophagus	ESCC	7.34e-12	5.50e-01	0.068
79577	CDC73	LZE24T	Human	Esophagus	ESCC	2.19e-17	5.52e-01	0.0596
79577	CDC73	LZE6T	Human	Esophagus	ESCC	8.01e-04	5.36e-02	0.0845
79577	CDC73	P1T-E	Human	Esophagus	ESCC	3.12e-06	4.08e-01	0.0875
79577	CDC73	P2T-E	Human	Esophagus	ESCC	9.50e-32	6.39e-01	0.1177
79577	CDC73	P4T-E	Human	Esophagus	ESCC	1.09e-30	7.81e-01	0.1323
79577	CDC73	P5T-E	Human	Esophagus	ESCC	1.15e-25	5.99e-01	0.1327
79577	CDC73	P8T-E	Human	Esophagus	ESCC	3.36e-23	3.21e-01	0.0889
79577	CDC73	P9T-E	Human	Esophagus	ESCC	5.11e-26	3.39e-01	0.1131
79577	CDC73	P10T-E	Human	Esophagus	ESCC	8.34e-20	4.79e-01	0.116
79577	CDC73	P11T-E	Human	Esophagus	ESCC	1.04e-20	6.96e-01	0.1426
79577	CDC73	P12T-E	Human	Esophagus	ESCC	6.11e-13	3.65e-01	0.1122
79577	CDC73	P15T-E	Human	Esophagus	ESCC	3.64e-24	6.27e-01	0.1149
79577	CDC73	P16T-E	Human	Esophagus	ESCC	1.56e-28	7.08e-01	0.1153

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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
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
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:003011110	Oral cavity	OSCC	regulation of Wnt signaling pathway	165/7305	328/18723	1.87e-05	1.80e-04	165
GO:00327843	Oral cavity	OSCC	regulation of DNA-templated transcription, elongation	36/7305	53/18723	1.89e-05	1.83e-04	36
GO:005067310	Oral cavity	OSCC	epithelial cell proliferation	212/7305	437/18723	2.82e-05	2.61e-04	212
GO:00342434	Oral cavity	OSCC	regulation of transcription elongation from RNA polymerase II promoter	24/7305	32/18723	3.83e-05	3.37e-04	24
GO:007122210	Oral cavity	OSCC	cellular response to lipopolysaccharide	110/7305	209/18723	4.15e-05	3.60e-04	110
GO:190370618	Oral cavity	OSCC	regulation of hemopoiesis	180/7305	367/18723	5.16e-05	4.30e-04	180
GO:00481446	Oral cavity	OSCC	fibroblast proliferation	49/7305	81/18723	7.27e-05	5.72e-04	49
GO:00074925	Oral cavity	OSCC	endoderm development	47/7305	77/18723	7.40e-05	5.81e-04	47
GO:19019895	Oral cavity	OSCC	positive regulation of cell cycle phase transition	65/7305	115/18723	1.03e-04	7.69e-04	65
GO:00481457	Oral cavity	OSCC	regulation of fibroblast proliferation	48/7305	80/18723	1.14e-04	8.35e-04	48
GO:007121910	Oral cavity	OSCC	cellular response to molecule of bacterial origin	112/7305	221/18723	2.64e-04	1.69e-03	112
GO:00017063	Oral cavity	OSCC	endoderm formation	34/7305	54/18723	3.12e-04	1.94e-03	34
GO:00073697	Oral cavity	OSCC	gastrulation	95/7305	185/18723	4.17e-04	2.54e-03	95
GO:004563720	Oral cavity	OSCC	regulation of myeloid cell differentiation	106/7305	210/18723	4.58e-04	2.76e-03	106
GO:005067810	Oral cavity	OSCC	regulation of epithelial cell proliferation	180/7305	381/18723	5.88e-04	3.35e-03	180
GO:00017043	Oral cavity	OSCC	formation of primary germ layer	65/7305	121/18723	7.08e-04	3.90e-03	65
GO:00316485	Oral cavity	OSCC	protein destabilization	29/7305	46/18723	8.26e-04	4.38e-03	29
GO:20000455	Oral cavity	OSCC	regulation of G1/S transition of mitotic cell cycle	74/7305	142/18723	1.01e-03	5.24e-03	74
GO:00301779	Oral cavity	OSCC	positive regulation of Wnt signaling pathway	73/7305	140/18723	1.06e-03	5.46e-03	73
GO:00359872	Oral cavity	OSCC	endodermal cell differentiation	28/7305	45/18723	1.36e-03	6.62e-03	28

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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

CDC73

SNV

Missense_Mutation

c.1073G>A

p.Arg358Gln

p.R358Q

Q6P1J9

protein_coding

deleterious(0.01)

probably_damaging(0.949)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CDC73

SNV

Missense_Mutation

c.1352N>T

p.Ala451Val

p.A451V

Q6P1J9

protein_coding

tolerated(0.06)

benign(0.119)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CDC73

SNV

Missense_Mutation

c.1019N>C

p.Val340Ala

p.V340A

Q6P1J9

protein_coding

tolerated(0.78)

benign(0.007)

TCGA-AN-A0FW-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

CDC73

SNV

Missense_Mutation

novel

c.1034N>A

p.Ser345Tyr

p.S345Y

Q6P1J9

protein_coding

tolerated(0.13)

probably_damaging(0.949)

TCGA-AR-A2LE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

CDC73

SNV

Missense_Mutation

novel

c.947N>T

p.His316Leu

p.H316L

Q6P1J9

protein_coding

deleterious(0.01)

probably_damaging(0.986)

TCGA-AR-A2LN-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

letrozole

CDC73

SNV

Missense_Mutation

c.1247N>A

p.Gly416Asp

p.G416D

Q6P1J9

protein_coding

deleterious(0.03)

benign(0.03)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

CDC73

SNV

Missense_Mutation

novel

c.1537N>T

p.Arg513Trp

p.R513W

Q6P1J9

protein_coding

deleterious(0.02)

possibly_damaging(0.562)

TCGA-BH-A5IZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

CDC73

SNV

Missense_Mutation

novel

c.72N>C

p.Glu24Asp

p.E24D

Q6P1J9

protein_coding

tolerated(0.2)

benign(0.003)

TCGA-S3-AA17-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

anastrozole

CDC73

SNV

Missense_Mutation

c.921N>G

p.Phe307Leu

p.F307L

Q6P1J9

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

CDC73

SNV

Missense_Mutation

rs878855091

c.787C>T

p.Arg263Cys

p.R263C

Q6P1J9

protein_coding

deleterious(0)

probably_damaging(0.964)

TCGA-MA-AA42-01

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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