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:00109061	Liver	Cirrhotic	regulation of glucose metabolic process	47/4634	119/18723	2.61e-04	2.33e-03	47
GO:00193191	Liver	Cirrhotic	hexose biosynthetic process	33/4634	78/18723	4.94e-04	3.96e-03	33
GO:00060941	Liver	Cirrhotic	gluconeogenesis	32/4634	75/18723	5.00e-04	3.98e-03	32
GO:00106751	Liver	Cirrhotic	regulation of cellular carbohydrate metabolic process	54/4634	146/18723	6.53e-04	4.96e-03	54
GO:00459121	Liver	Cirrhotic	negative regulation of carbohydrate metabolic process	20/4634	48/18723	7.37e-03	3.52e-02	20
GO:00106771	Liver	Cirrhotic	negative regulation of cellular carbohydrate metabolic process	18/4634	42/18723	7.64e-03	3.61e-02	18
GO:000599621	Liver	HCC	monosaccharide metabolic process	167/7958	257/18723	2.31e-13	1.25e-11	167
GO:001931821	Liver	HCC	hexose metabolic process	155/7958	237/18723	7.63e-13	3.90e-11	155
GO:000600621	Liver	HCC	glucose metabolic process	128/7958	196/18723	8.60e-11	3.06e-09	128
GO:006201222	Liver	HCC	regulation of small molecule metabolic process	190/7958	334/18723	6.77e-08	1.40e-06	190
GO:00463642	Liver	HCC	monosaccharide biosynthetic process	58/7958	82/18723	2.08e-07	3.75e-06	58
GO:000610921	Liver	HCC	regulation of carbohydrate metabolic process	109/7958	178/18723	3.36e-07	5.78e-06	109
GO:00193192	Liver	HCC	hexose biosynthetic process	54/7958	78/18723	1.61e-06	2.27e-05	54
GO:00109062	Liver	HCC	regulation of glucose metabolic process	76/7958	119/18723	2.03e-06	2.79e-05	76
GO:00060942	Liver	HCC	gluconeogenesis	52/7958	75/18723	2.34e-06	3.14e-05	52
GO:00106752	Liver	HCC	regulation of cellular carbohydrate metabolic process	88/7958	146/18723	1.08e-05	1.24e-04	88
GO:004426221	Liver	HCC	cellular carbohydrate metabolic process	153/7958	283/18723	5.27e-05	5.00e-04	153
GO:00160512	Liver	HCC	carbohydrate biosynthetic process	113/7958	202/18723	7.64e-05	6.83e-04	113
GO:00106772	Liver	HCC	negative regulation of cellular carbohydrate metabolic process	28/7958	42/18723	1.35e-03	7.26e-03	28
GO:00061111	Liver	HCC	regulation of gluconeogenesis	31/7958	48/18723	1.66e-03	8.71e-03	31

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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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