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: FAM3C

Gene summary for FAM3C

Gene summary.

Gene information	Species	Human
	Gene symbol	FAM3C
	Gene ID	10447
	Gene name	FAM3 metabolism regulating signaling molecule C
	Gene Alias	GS3786
	Cytomap	7q31.31
	Gene Type	protein-coding
	GO ID	GO:0005975
	UniProtAcc	Q92520

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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
10447	FAM3C	LZE3D	Human	Esophagus	HGIN	2.17e-02	1.42e-01	0.0668
10447	FAM3C	LZE4T	Human	Esophagus	ESCC	2.99e-03	2.03e-01	0.0811
10447	FAM3C	LZE5T	Human	Esophagus	ESCC	8.07e-09	1.01e+00	0.0514
10447	FAM3C	LZE7T	Human	Esophagus	ESCC	8.23e-04	3.03e-01	0.0667
10447	FAM3C	LZE8T	Human	Esophagus	ESCC	1.61e-14	5.65e-01	0.067
10447	FAM3C	LZE20T	Human	Esophagus	ESCC	1.18e-14	1.14e+00	0.0662
10447	FAM3C	LZE22D1	Human	Esophagus	HGIN	1.89e-04	-1.81e-01	0.0595
10447	FAM3C	LZE22T	Human	Esophagus	ESCC	2.01e-04	5.12e-01	0.068
10447	FAM3C	LZE24T	Human	Esophagus	ESCC	2.42e-14	7.59e-01	0.0596
10447	FAM3C	LZE21T	Human	Esophagus	ESCC	2.28e-04	3.99e-01	0.0655
10447	FAM3C	LZE6T	Human	Esophagus	ESCC	4.55e-04	-1.72e-01	0.0845
10447	FAM3C	P1T-E	Human	Esophagus	ESCC	1.01e-05	1.07e+00	0.0875
10447	FAM3C	P2T-E	Human	Esophagus	ESCC	2.21e-18	2.50e-01	0.1177
10447	FAM3C	P4T-E	Human	Esophagus	ESCC	6.56e-40	1.16e+00	0.1323
10447	FAM3C	P5T-E	Human	Esophagus	ESCC	7.72e-26	7.06e-01	0.1327
10447	FAM3C	P8T-E	Human	Esophagus	ESCC	9.19e-80	1.68e+00	0.0889
10447	FAM3C	P9T-E	Human	Esophagus	ESCC	3.77e-13	5.11e-01	0.1131
10447	FAM3C	P10T-E	Human	Esophagus	ESCC	1.03e-36	7.47e-01	0.116
10447	FAM3C	P11T-E	Human	Esophagus	ESCC	1.40e-17	1.05e+00	0.1426
10447	FAM3C	P12T-E	Human	Esophagus	ESCC	1.08e-77	1.90e+00	0.1122

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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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:00059969	Esophagus	ESCC	monosaccharide metabolic process	159/8552	257/18723	1.11e-07	1.81e-06	159
GO:00193189	Esophagus	ESCC	hexose metabolic process	147/8552	237/18723	2.63e-07	3.94e-06	147
GO:00060069	Esophagus	ESCC	glucose metabolic process	119/8552	196/18723	1.51e-05	1.36e-04	119
GO:00442626	Esophagus	ESCC	cellular carbohydrate metabolic process	160/8552	283/18723	1.43e-04	9.66e-04	160
GO:00160514	Esophagus	ESCC	carbohydrate biosynthetic process	117/8552	202/18723	2.96e-04	1.79e-03	117
GO:00620129	Esophagus	ESCC	regulation of small molecule metabolic process	184/8552	334/18723	3.11e-04	1.85e-03	184
GO:00463643	Esophagus	ESCC	monosaccharide biosynthetic process	52/8552	82/18723	9.03e-04	4.61e-03	52
GO:00109065	Esophagus	ESCC	regulation of glucose metabolic process	71/8552	119/18723	1.46e-03	6.92e-03	71
GO:00193193	Esophagus	ESCC	hexose biosynthetic process	49/8552	78/18723	1.69e-03	7.81e-03	49
GO:00061096	Esophagus	ESCC	regulation of carbohydrate metabolic process	101/8552	178/18723	1.89e-03	8.52e-03	101
GO:00106755	Esophagus	ESCC	regulation of cellular carbohydrate metabolic process	83/8552	146/18723	4.24e-03	1.69e-02	83
GO:00060943	Esophagus	ESCC	gluconeogenesis	46/8552	75/18723	4.54e-03	1.78e-02	46
GO:000599612	Liver	Cirrhotic	monosaccharide metabolic process	104/4634	257/18723	1.74e-08	6.32e-07	104
GO:001931812	Liver	Cirrhotic	hexose metabolic process	97/4634	237/18723	2.67e-08	9.16e-07	97
GO:000600611	Liver	Cirrhotic	glucose metabolic process	82/4634	196/18723	1.01e-07	2.93e-06	82
GO:006201212	Liver	Cirrhotic	regulation of small molecule metabolic process	124/4634	334/18723	2.74e-07	6.79e-06	124
GO:000610911	Liver	Cirrhotic	regulation of carbohydrate metabolic process	70/4634	178/18723	1.14e-05	1.62e-04	70
GO:00463641	Liver	Cirrhotic	monosaccharide biosynthetic process	37/4634	82/18723	4.52e-05	5.30e-04	37
GO:004426211	Liver	Cirrhotic	cellular carbohydrate metabolic process	97/4634	283/18723	1.89e-04	1.76e-03	97
GO:00160511	Liver	Cirrhotic	carbohydrate biosynthetic process	73/4634	202/18723	1.91e-04	1.77e-03	73

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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

FAM3C

SNV

Missense_Mutation

novel

c.667C>T

p.Pro223Ser

p.P223S

Q92520

protein_coding

deleterious(0.02)

probably_damaging(0.976)

TCGA-A7-A3IZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

FAM3C

SNV

Missense_Mutation

c.117N>G

p.Phe39Leu

p.F39L

Q92520

protein_coding

tolerated(0.39)

benign(0.003)

TCGA-BH-A0BG-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FAM3C

SNV

Missense_Mutation

novel

c.164G>T

p.Arg55Ile

p.R55I

Q92520

protein_coding

deleterious(0)

benign(0.288)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

FAM3C

SNV

Missense_Mutation

novel

c.71C>A

p.Ser24Tyr

p.S24Y

Q92520

protein_coding

tolerated(0.91)

benign(0.162)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

FAM3C

SNV

Missense_Mutation

novel

c.451G>A

p.Asp151Asn

p.D151N

Q92520

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

FAM3C

SNV

Missense_Mutation

novel

c.411G>T

p.Lys137Asn

p.K137N

Q92520

protein_coding

deleterious(0.03)

benign(0.042)

TCGA-A5-A0G1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

FAM3C

SNV

Missense_Mutation

novel

c.509G>T

p.Ser170Ile

p.S170I

Q92520

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

FAM3C

SNV

Missense_Mutation

rs772971347

c.488G>A

p.Arg163Gln

p.R163Q

Q92520

protein_coding

tolerated(0.12)

benign(0.006)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

FAM3C

SNV

Missense_Mutation

c.291N>T

p.Lys97Asn

p.K97N

Q92520

protein_coding

deleterious(0.03)

benign(0.251)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

FAM3C

SNV

Missense_Mutation

c.88A>C

p.Lys30Gln

p.K30Q

Q92520

protein_coding

tolerated(0.53)

benign(0.444)

TCGA-AX-A0J0-01

Endometrium

uterine corpus endometrioid carcinoma

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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