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:00359873	Esophagus	ESCC	endodermal cell differentiation	32/8552	45/18723	4.87e-04	2.70e-03	32
GO:005067817	Esophagus	ESCC	regulation of epithelial cell proliferation	206/8552	381/18723	5.51e-04	3.02e-03	206
GO:003296812	Esophagus	ESCC	positive regulation of transcription elongation from RNA polymerase II promoter	12/8552	13/18723	6.18e-04	3.32e-03	12
GO:0045637111	Esophagus	ESCC	regulation of myeloid cell differentiation	118/8552	210/18723	1.35e-03	6.43e-03	118
GO:000223719	Esophagus	ESCC	response to molecule of bacterial origin	194/8552	363/18723	1.64e-03	7.61e-03	194
GO:00481471	Esophagus	ESCC	negative regulation of fibroblast proliferation	22/8552	30/18723	1.98e-03	8.90e-03	22
GO:200004513	Esophagus	ESCC	regulation of G1/S transition of mitotic cell cycle	82/8552	142/18723	2.49e-03	1.08e-02	82
GO:190280613	Esophagus	ESCC	regulation of cell cycle G1/S phase transition	95/8552	168/18723	2.91e-03	1.22e-02	95
GO:007122215	Esophagus	ESCC	cellular response to lipopolysaccharide	113/8552	209/18723	8.79e-03	3.10e-02	113
GO:007121617	Esophagus	ESCC	cellular response to biotic stimulus	131/8552	246/18723	9.85e-03	3.39e-02	131
GO:19033116	Liver	NAFLD	regulation of mRNA metabolic process	66/1882	288/18723	1.06e-10	2.96e-08	66
GO:00165703	Liver	NAFLD	histone modification	90/1882	463/18723	5.74e-10	1.28e-07	90
GO:00316477	Liver	NAFLD	regulation of protein stability	61/1882	298/18723	5.00e-08	4.71e-06	61
GO:00160495	Liver	NAFLD	cell growth	85/1882	482/18723	1.75e-07	1.25e-05	85
GO:00506846	Liver	NAFLD	regulation of mRNA processing	33/1882	137/18723	1.47e-06	6.73e-05	33
GO:00160555	Liver	NAFLD	Wnt signaling pathway	74/1882	444/18723	8.98e-06	2.96e-04	74
GO:01987385	Liver	NAFLD	cell-cell signaling by wnt	74/1882	446/18723	1.05e-05	3.33e-04	74
GO:00226137	Liver	NAFLD	ribonucleoprotein complex biogenesis	76/1882	463/18723	1.19e-05	3.67e-04	76
GO:19033134	Liver	NAFLD	positive regulation of mRNA metabolic process	28/1882	118/18723	1.21e-05	3.70e-04	28
GO:00301115	Liver	NAFLD	regulation of Wnt signaling pathway	57/1882	328/18723	2.79e-05	7.46e-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

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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