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:002261327	Esophagus	HGIN	ribonucleoprotein complex biogenesis	158/2587	463/18723	2.61e-29	5.23e-26	158
GO:007182627	Esophagus	HGIN	ribonucleoprotein complex subunit organization	84/2587	227/18723	1.34e-18	5.37e-16	84
GO:002261827	Esophagus	HGIN	ribonucleoprotein complex assembly	82/2587	220/18723	2.07e-18	7.36e-16	82
GO:003164727	Esophagus	HGIN	regulation of protein stability	96/2587	298/18723	2.21e-16	5.76e-14	96
GO:190331120	Esophagus	HGIN	regulation of mRNA metabolic process	91/2587	288/18723	5.06e-15	9.78e-13	91
GO:005068419	Esophagus	HGIN	regulation of mRNA processing	55/2587	137/18723	2.17e-14	3.94e-12	55
GO:190331310	Esophagus	HGIN	positive regulation of mRNA metabolic process	38/2587	118/18723	2.46e-07	1.16e-05	38
GO:00198277	Esophagus	HGIN	stem cell population maintenance	39/2587	131/18723	1.63e-06	6.14e-05	39
GO:00987278	Esophagus	HGIN	maintenance of cell number	39/2587	134/18723	3.02e-06	1.03e-04	39
GO:000734610	Esophagus	HGIN	regulation of mitotic cell cycle	98/2587	457/18723	4.39e-06	1.42e-04	98
GO:00506855	Esophagus	HGIN	positive regulation of mRNA processing	15/2587	32/18723	6.76e-06	2.08e-04	15
GO:00063687	Esophagus	HGIN	transcription elongation from RNA polymerase II promoter	24/2587	69/18723	8.93e-06	2.64e-04	24
GO:003009927	Esophagus	HGIN	myeloid cell differentiation	83/2587	381/18723	1.26e-05	3.52e-04	83
GO:00447729	Esophagus	HGIN	mitotic cell cycle phase transition	89/2587	424/18723	2.80e-05	7.21e-04	89
GO:00063548	Esophagus	HGIN	DNA-templated transcription, elongation	27/2587	91/18723	6.62e-05	1.52e-03	27
GO:19019906	Esophagus	HGIN	regulation of mitotic cell cycle phase transition	65/2587	299/18723	1.12e-04	2.36e-03	65
GO:004563725	Esophagus	HGIN	regulation of myeloid cell differentiation	49/2587	210/18723	1.28e-04	2.61e-03	49
GO:00165708	Esophagus	HGIN	histone modification	92/2587	463/18723	1.70e-04	3.30e-03	92
GO:00342435	Esophagus	HGIN	regulation of transcription elongation from RNA polymerase II promoter	13/2587	32/18723	1.72e-04	3.32e-03	13
GO:20000456	Esophagus	HGIN	regulation of G1/S transition of mitotic cell cycle	36/2587	142/18723	1.74e-04	3.35e-03	36

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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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