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: APOBEC3C

Gene summary for APOBEC3C

Gene summary.

Gene information	Species	Human
	Gene symbol	APOBEC3C
	Gene ID	27350
	Gene name	apolipoprotein B mRNA editing enzyme catalytic subunit 3C
	Gene Alias	A3C
	Cytomap	22q13.1
	Gene Type	protein-coding
	GO ID	GO:0002376
	UniProtAcc	Q9NRW3

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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
27350	APOBEC3C	HTA11_2487_2000001011	Human	Colorectum	SER	9.88e-04	1.62e-01	-0.1808
27350	APOBEC3C	HTA11_1938_2000001011	Human	Colorectum	AD	9.49e-04	1.98e-01	-0.0811
27350	APOBEC3C	HTA11_347_2000001011	Human	Colorectum	AD	1.18e-22	4.15e-01	-0.1954
27350	APOBEC3C	HTA11_411_2000001011	Human	Colorectum	SER	4.42e-10	5.69e-01	-0.2602
27350	APOBEC3C	HTA11_3361_2000001011	Human	Colorectum	AD	5.46e-03	2.67e-01	-0.1207
27350	APOBEC3C	HTA11_696_2000001011	Human	Colorectum	AD	2.46e-16	3.75e-01	-0.1464
27350	APOBEC3C	HTA11_866_2000001011	Human	Colorectum	AD	4.46e-07	1.89e-01	-0.1001
27350	APOBEC3C	HTA11_2992_2000001011	Human	Colorectum	SER	2.03e-15	6.42e-01	-0.1706
27350	APOBEC3C	HTA11_5212_2000001011	Human	Colorectum	AD	3.97e-04	2.59e-01	-0.2061
27350	APOBEC3C	HTA11_7862_2000001011	Human	Colorectum	AD	1.24e-02	1.79e-01	-0.0179
27350	APOBEC3C	HTA11_8622_2000001021	Human	Colorectum	SER	8.37e-05	2.47e-01	0.0528
27350	APOBEC3C	HTA11_6818_2000001021	Human	Colorectum	AD	1.15e-02	1.58e-01	0.0588
27350	APOBEC3C	HTA11_99999970781_79442	Human	Colorectum	MSS	9.63e-08	1.74e-01	0.294
27350	APOBEC3C	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.40e-05	6.32e-01	0.3487
27350	APOBEC3C	HTA11_99999971662_82457	Human	Colorectum	MSS	4.38e-06	1.42e-01	0.3859
27350	APOBEC3C	HTA11_99999974143_84620	Human	Colorectum	MSS	9.10e-25	4.69e-01	0.3005
27350	APOBEC3C	LZE4T	Human	Esophagus	ESCC	1.26e-05	1.79e-01	0.0811
27350	APOBEC3C	LZE8T	Human	Esophagus	ESCC	7.07e-03	1.94e-02	0.067
27350	APOBEC3C	LZE6T	Human	Esophagus	ESCC	7.16e-04	2.86e-01	0.0845
27350	APOBEC3C	P2T-E	Human	Esophagus	ESCC	5.49e-25	1.52e-01	0.1177

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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

∗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:0016032	Colorectum	AD	viral process	168/3918	415/18723	4.67e-20	3.66e-17	168
GO:0019058	Colorectum	AD	viral life cycle	119/3918	317/18723	6.18e-12	8.23e-10	119
GO:0044270	Colorectum	AD	cellular nitrogen compound catabolic process	147/3918	451/18723	3.35e-09	2.23e-07	147
GO:0046700	Colorectum	AD	heterocycle catabolic process	145/3918	445/18723	4.37e-09	2.84e-07	145
GO:0034655	Colorectum	AD	nucleobase-containing compound catabolic process	133/3918	407/18723	1.56e-08	9.12e-07	133
GO:0019439	Colorectum	AD	aromatic compound catabolic process	146/3918	467/18723	7.48e-08	3.84e-06	146
GO:1901361	Colorectum	AD	organic cyclic compound catabolic process	153/3918	495/18723	8.23e-08	4.18e-06	153
GO:0044282	Colorectum	AD	small molecule catabolic process	118/3918	376/18723	1.05e-06	3.55e-05	118
GO:0019079	Colorectum	AD	viral genome replication	51/3918	131/18723	1.83e-06	5.51e-05	51
GO:0050792	Colorectum	AD	regulation of viral process	59/3918	164/18723	5.95e-06	1.52e-04	59
GO:1903900	Colorectum	AD	regulation of viral life cycle	51/3918	148/18723	9.01e-05	1.38e-03	51
GO:0045069	Colorectum	AD	regulation of viral genome replication	32/3918	85/18723	2.97e-04	3.60e-03	32
GO:00160321	Colorectum	SER	viral process	118/2897	415/18723	8.36e-12	1.65e-09	118
GO:00190581	Colorectum	SER	viral life cycle	87/2897	317/18723	2.82e-08	1.94e-06	87
GO:00442821	Colorectum	SER	small molecule catabolic process	87/2897	376/18723	5.31e-05	1.27e-03	87
GO:00190791	Colorectum	SER	viral genome replication	37/2897	131/18723	1.36e-04	2.72e-03	37
GO:00442701	Colorectum	SER	cellular nitrogen compound catabolic process	99/2897	451/18723	1.46e-04	2.86e-03	99
GO:00467001	Colorectum	SER	heterocycle catabolic process	97/2897	445/18723	2.20e-04	3.89e-03	97
GO:00507921	Colorectum	SER	regulation of viral process	43/2897	164/18723	2.57e-04	4.31e-03	43
GO:19013611	Colorectum	SER	organic cyclic compound catabolic process	104/2897	495/18723	5.46e-04	7.63e-03	104

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05170	Colorectum	AD	Human immunodeficiency virus 1 infection	72/2092	212/8465	1.40e-03	8.46e-03	5.39e-03	72
hsa051701	Colorectum	AD	Human immunodeficiency virus 1 infection	72/2092	212/8465	1.40e-03	8.46e-03	5.39e-03	72
hsa051702	Colorectum	SER	Human immunodeficiency virus 1 infection	58/1580	212/8465	1.08e-03	8.56e-03	6.21e-03	58
hsa051703	Colorectum	SER	Human immunodeficiency virus 1 infection	58/1580	212/8465	1.08e-03	8.56e-03	6.21e-03	58
hsa051704	Colorectum	MSS	Human immunodeficiency virus 1 infection	69/1875	212/8465	2.66e-04	1.98e-03	1.21e-03	69
hsa051705	Colorectum	MSS	Human immunodeficiency virus 1 infection	69/1875	212/8465	2.66e-04	1.98e-03	1.21e-03	69
hsa032509	Esophagus	ESCC	Viral life cycle - HIV-1	54/4205	63/8465	2.01e-09	2.17e-08	1.11e-08	54
hsa05170210	Esophagus	ESCC	Human immunodeficiency virus 1 infection	147/4205	212/8465	3.37e-09	3.53e-08	1.81e-08	147
hsa0325014	Esophagus	ESCC	Viral life cycle - HIV-1	54/4205	63/8465	2.01e-09	2.17e-08	1.11e-08	54
hsa0517038	Esophagus	ESCC	Human immunodeficiency virus 1 infection	147/4205	212/8465	3.37e-09	3.53e-08	1.81e-08	147
hsa0517027	Oral cavity	OSCC	Human immunodeficiency virus 1 infection	133/3704	212/8465	1.42e-08	1.40e-07	7.12e-08	133
hsa032508	Oral cavity	OSCC	Viral life cycle - HIV-1	45/3704	63/8465	7.62e-06	3.59e-05	1.83e-05	45
hsa05170111	Oral cavity	OSCC	Human immunodeficiency virus 1 infection	133/3704	212/8465	1.42e-08	1.40e-07	7.12e-08	133
hsa0325013	Oral cavity	OSCC	Viral life cycle - HIV-1	45/3704	63/8465	7.62e-06	3.59e-05	1.83e-05	45
hsa0517028	Oral cavity	LP	Human immunodeficiency virus 1 infection	92/2418	212/8465	2.18e-06	2.20e-05	1.42e-05	92
hsa0517037	Oral cavity	LP	Human immunodeficiency virus 1 infection	92/2418	212/8465	2.18e-06	2.20e-05	1.42e-05	92

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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

APOBEC3C

SNV

Missense_Mutation

rs200673371

c.131G>A

p.Arg44His

p.R44H

Q9NRW3

protein_coding

tolerated(0.93)

benign(0)

TCGA-AQ-A04J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

APOBEC3C

SNV

Missense_Mutation

c.472N>A

p.Glu158Lys

p.E158K

Q9NRW3

protein_coding

tolerated(0.3)

benign(0.012)

TCGA-D8-A1XT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin+cyclophosphamide

APOBEC3C

insertion

In_Frame_Ins

novel

c.120_121insATTCTCAGGGCTGTGGAGGGATGGGGGAGGCCCAGAGCCCAG

p.Glu40_Gly41insIleLeuArgAlaValGluGlyTrpGlyArgProArgAlaGln

p.E40_G41insILRAVEGWGRPRAQ

Q9NRW3

protein_coding

TCGA-AN-A04D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

APOBEC3C

insertion

In_Frame_Ins

novel

c.132_133insATT

p.Arg44_Arg45insIle

p.R44_R45insI

Q9NRW3

protein_coding

TCGA-AQ-A04J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

APOBEC3C

insertion

Frame_Shift_Ins

novel

c.136_137insGTTTCACATTTTCTTGGTCCACACGGAAC

p.Ser46CysfsTer79

p.S46Cfs*79

Q9NRW3

protein_coding

TCGA-B6-A0IA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

APOBEC3C

SNV

Missense_Mutation

rs376538641

c.134N>A

p.Arg45His

p.R45H

Q9NRW3

protein_coding

tolerated(0.23)

benign(0.001)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

APOBEC3C

SNV

Missense_Mutation

c.130N>T

p.Arg44Cys

p.R44C

Q9NRW3

protein_coding

tolerated(0.19)

benign(0)

TCGA-EA-A3HS-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

APOBEC3C

SNV

Missense_Mutation

rs756657821

c.160G>A

p.Val54Ile

p.V54I

Q9NRW3

protein_coding

tolerated(0.45)

benign(0.353)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

APOBEC3C

SNV

Missense_Mutation

c.365G>A

p.Arg122His

p.R122H

Q9NRW3

protein_coding

deleterious(0.03)

probably_damaging(0.948)

TCGA-AA-A01R-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

5-fluorouracil

APOBEC3C

SNV

Missense_Mutation

novel

c.403N>T

p.Leu135Phe

p.L135F

Q9NRW3

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<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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