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: FAM162A

Gene summary for FAM162A

Gene summary.

Gene information	Species	Human
	Gene symbol	FAM162A
	Gene ID	26355
	Gene name	family with sequence similarity 162 member A
	Gene Alias	C3orf28
	Cytomap	3q21.1
	Gene Type	protein-coding
	GO ID	GO:0001666
	UniProtAcc	Q96A26

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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
26355	FAM162A	GSM4909285	Human	Breast	IDC	8.06e-08	4.77e-01	0.21
26355	FAM162A	GSM4909293	Human	Breast	IDC	4.48e-03	2.32e-01	0.1581
26355	FAM162A	GSM4909296	Human	Breast	IDC	8.51e-05	4.91e-02	0.1524
26355	FAM162A	GSM4909297	Human	Breast	IDC	7.58e-12	-2.39e-02	0.1517
26355	FAM162A	GSM4909306	Human	Breast	IDC	3.38e-04	3.38e-01	0.1564
26355	FAM162A	GSM4909308	Human	Breast	IDC	6.34e-03	3.47e-01	0.158
26355	FAM162A	GSM4909311	Human	Breast	IDC	1.40e-15	-2.35e-01	0.1534
26355	FAM162A	GSM4909312	Human	Breast	IDC	4.41e-06	-1.43e-01	0.1552
26355	FAM162A	GSM4909315	Human	Breast	IDC	2.72e-34	8.83e-01	0.21
26355	FAM162A	GSM4909316	Human	Breast	IDC	6.22e-08	4.43e-01	0.21
26355	FAM162A	GSM4909319	Human	Breast	IDC	1.30e-23	-1.68e-01	0.1563
26355	FAM162A	GSM4909320	Human	Breast	IDC	4.57e-04	-1.48e-02	0.1575
26355	FAM162A	GSM4909321	Human	Breast	IDC	1.19e-10	-8.51e-02	0.1559
26355	FAM162A	ctrl6	Human	Breast	Precancer	4.64e-10	6.56e-01	-0.0061
26355	FAM162A	brca3	Human	Breast	Precancer	1.15e-07	4.27e-01	-0.0263
26355	FAM162A	brca7	Human	Breast	Precancer	1.08e-02	6.55e-01	-0.009
26355	FAM162A	brca10	Human	Breast	Precancer	9.00e-10	5.47e-01	-0.0029
26355	FAM162A	M2	Human	Breast	IDC	1.65e-02	2.96e-01	0.21
26355	FAM162A	M5	Human	Breast	IDC	4.56e-03	5.67e-01	0.1598
26355	FAM162A	NCCBC11	Human	Breast	DCIS	5.82e-04	4.23e-01	0.1232

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
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:00901996	Breast	Precancer	regulation of release of cytochrome c from mitochondria	10/1080	48/18723	3.43e-04	4.81e-03	10
GO:00108217	Breast	Precancer	regulation of mitochondrion organization	19/1080	144/18723	6.26e-04	7.78e-03	19
GO:0090200	Breast	Precancer	positive regulation of release of cytochrome c from mitochondria	6/1080	28/18723	4.58e-03	3.53e-02	6
GO:005254714	Breast	IDC	regulation of peptidase activity	96/1434	461/18723	7.58e-20	6.15e-17	96
GO:005254814	Breast	IDC	regulation of endopeptidase activity	88/1434	432/18723	1.20e-17	4.85e-15	88
GO:200011614	Breast	IDC	regulation of cysteine-type endopeptidase activity	55/1434	235/18723	4.25e-14	1.21e-11	55
GO:004328114	Breast	IDC	regulation of cysteine-type endopeptidase activity involved in apoptotic process	50/1434	209/18723	2.49e-13	6.14e-11	50
GO:007048214	Breast	IDC	response to oxygen levels	64/1434	347/18723	3.45e-11	5.57e-09	64
GO:003629314	Breast	IDC	response to decreased oxygen levels	60/1434	322/18723	9.26e-11	1.25e-08	60
GO:004586214	Breast	IDC	positive regulation of proteolysis	66/1434	372/18723	9.76e-11	1.29e-08	66
GO:000166614	Breast	IDC	response to hypoxia	58/1434	307/18723	1.09e-10	1.38e-08	58
GO:001095214	Breast	IDC	positive regulation of peptidase activity	40/1434	197/18723	1.04e-08	7.67e-07	40
GO:000863713	Breast	IDC	apoptotic mitochondrial changes	27/1434	107/18723	2.29e-08	1.57e-06	27
GO:003629413	Breast	IDC	cellular response to decreased oxygen levels	34/1434	161/18723	4.73e-08	3.02e-06	34
GO:007145613	Breast	IDC	cellular response to hypoxia	32/1434	151/18723	1.07e-07	6.26e-06	32
GO:004328013	Breast	IDC	positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	29/1434	129/18723	1.10e-07	6.35e-06	29
GO:007099714	Breast	IDC	neuron death	57/1434	361/18723	1.31e-07	7.38e-06	57
GO:007145313	Breast	IDC	cellular response to oxygen levels	35/1434	177/18723	1.68e-07	9.10e-06	35
GO:200105613	Breast	IDC	positive regulation of cysteine-type endopeptidase activity	31/1434	148/18723	2.22e-07	1.17e-05	31
GO:001095013	Breast	IDC	positive regulation of endopeptidase activity	35/1434	179/18723	2.24e-07	1.17e-05	35

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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

FAM162A

SNV

Missense_Mutation

novel

c.392N>T

p.Thr131Ile

p.T131I

Q96A26

protein_coding

deleterious(0)

benign(0.037)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FAM162A

SNV

Missense_Mutation

c.175N>T

p.Pro59Ser

p.P59S

Q96A26

protein_coding

deleterious(0)

probably_damaging(0.926)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FAM162A

SNV

Missense_Mutation

c.102N>C

p.Leu34Phe

p.L34F

Q96A26

protein_coding

tolerated(0.07)

benign(0.037)

TCGA-D8-A1JN-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozolum

FAM162A

SNV

Missense_Mutation

c.107G>T

p.Arg36Ile

p.R36I

Q96A26

protein_coding

tolerated(0.55)

benign(0.003)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

FAM162A

SNV

Missense_Mutation

c.452N>T

p.Ala151Val

p.A151V

Q96A26

protein_coding

deleterious(0)

possibly_damaging(0.795)

TCGA-AA-A01P-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

FAM162A

SNV

Missense_Mutation

novel

c.402N>A

p.Ser134Arg

p.S134R

Q96A26

protein_coding

tolerated(0.08)

benign(0.017)

TCGA-A5-A0G1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

FAM162A

SNV

Missense_Mutation

rs149572114

c.227N>A

p.Arg76His

p.R76H

Q96A26

protein_coding

tolerated(0.15)

benign(0.146)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

FAM162A

SNV

Missense_Mutation

c.107N>A

p.Arg36Lys

p.R36K

Q96A26

protein_coding

tolerated(0.52)

benign(0.122)

TCGA-AX-A0J0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

FAM162A

SNV

Missense_Mutation

novel

c.451N>A

p.Ala151Thr

p.A151T

Q96A26

protein_coding

deleterious(0)

possibly_damaging(0.589)

TCGA-DF-A2KN-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

FAM162A

SNV

Missense_Mutation

novel

c.299G>A

p.Arg100Gln

p.R100Q

Q96A26

protein_coding

deleterious(0.03)

probably_damaging(0.971)

TCGA-E6-A1LX-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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