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: SERINC2

Gene summary for SERINC2

Gene summary.

Gene information	Species	Human
	Gene symbol	SERINC2
	Gene ID	347735
	Gene name	serine incorporator 2
	Gene Alias	FKSG84
	Cytomap	1p35.2
	Gene Type	protein-coding
	GO ID	GO:0006575
	UniProtAcc	Q96IM8

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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
347735	SERINC2	GSM4909285	Human	Breast	IDC	1.49e-03	-3.06e-01	0.21
347735	SERINC2	GSM4909288	Human	Breast	IDC	3.17e-02	-3.91e-01	0.0988
347735	SERINC2	GSM4909291	Human	Breast	IDC	7.07e-15	-5.03e-01	0.1753
347735	SERINC2	GSM4909293	Human	Breast	IDC	2.10e-08	3.62e-01	0.1581
347735	SERINC2	GSM4909294	Human	Breast	IDC	2.11e-02	-4.18e-02	0.2022
347735	SERINC2	GSM4909296	Human	Breast	IDC	2.17e-07	-1.91e-01	0.1524
347735	SERINC2	GSM4909297	Human	Breast	IDC	1.03e-20	4.95e-02	0.1517
347735	SERINC2	GSM4909309	Human	Breast	IDC	6.87e-07	-3.35e-01	0.0483
347735	SERINC2	GSM4909311	Human	Breast	IDC	2.50e-28	-9.01e-02	0.1534
347735	SERINC2	GSM4909312	Human	Breast	IDC	5.16e-11	2.89e-01	0.1552
347735	SERINC2	GSM4909313	Human	Breast	IDC	7.53e-03	-1.98e-02	0.0391
347735	SERINC2	GSM4909319	Human	Breast	IDC	9.30e-50	4.13e-02	0.1563
347735	SERINC2	GSM4909320	Human	Breast	IDC	6.78e-06	-3.03e-01	0.1575
347735	SERINC2	GSM4909321	Human	Breast	IDC	6.64e-12	-2.17e-01	0.1559
347735	SERINC2	brca2	Human	Breast	Precancer	1.93e-08	4.23e-01	-0.024
347735	SERINC2	brca3	Human	Breast	Precancer	4.69e-11	4.57e-01	-0.0263
347735	SERINC2	brca10	Human	Breast	Precancer	8.29e-03	3.14e-01	-0.0029
347735	SERINC2	NCCBC14	Human	Breast	DCIS	9.54e-14	-1.75e-01	0.2021
347735	SERINC2	NCCBC2	Human	Breast	DCIS	2.63e-05	-2.46e-01	0.1554
347735	SERINC2	NCCBC3	Human	Breast	DCIS	2.59e-03	-2.47e-01	0.1198

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
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:00065755	Cervix	HSIL_HPV	cellular modified amino acid metabolic process	16/737	188/18723	3.18e-03	2.89e-02	16
GO:0006575	Colorectum	AD	cellular modified amino acid metabolic process	59/3918	188/18723	4.80e-04	5.27e-03	59
GO:0006650	Colorectum	AD	glycerophospholipid metabolic process	83/3918	306/18723	5.40e-03	3.55e-02	83
GO:0006644	Colorectum	AD	phospholipid metabolic process	101/3918	383/18723	5.80e-03	3.67e-02	101
GO:0046486	Colorectum	SER	glycerolipid metabolic process	82/2897	392/18723	2.26e-03	2.17e-02	82
GO:00066441	Colorectum	SER	phospholipid metabolic process	79/2897	383/18723	3.94e-03	3.24e-02	79
GO:00066501	Colorectum	SER	glycerophospholipid metabolic process	64/2897	306/18723	6.41e-03	4.60e-02	64
GO:00065751	Colorectum	MSS	cellular modified amino acid metabolic process	55/3467	188/18723	2.16e-04	3.01e-03	55
GO:00066502	Colorectum	FAP	glycerophospholipid metabolic process	62/2622	306/18723	1.54e-03	1.38e-02	62
GO:00066442	Colorectum	FAP	phospholipid metabolic process	74/2622	383/18723	2.24e-03	1.83e-02	74
GO:0006658	Colorectum	FAP	phosphatidylserine metabolic process	9/2622	25/18723	5.01e-03	3.33e-02	9
GO:00066503	Colorectum	CRC	glycerophospholipid metabolic process	55/2078	306/18723	2.10e-04	3.55e-03	55
GO:00066443	Colorectum	CRC	phospholipid metabolic process	65/2078	383/18723	3.21e-04	4.95e-03	65
GO:00464861	Colorectum	CRC	glycerolipid metabolic process	64/2078	392/18723	1.01e-03	1.19e-02	64
GO:00066581	Colorectum	CRC	phosphatidylserine metabolic process	8/2078	25/18723	4.33e-03	3.47e-02	8
GO:00066433	Esophagus	ESCC	membrane lipid metabolic process	130/8552	203/18723	9.29e-08	1.54e-06	130
GO:00066446	Esophagus	ESCC	phospholipid metabolic process	218/8552	383/18723	5.37e-06	5.59e-05	218
GO:00066652	Esophagus	ESCC	sphingolipid metabolic process	96/8552	155/18723	3.21e-05	2.66e-04	96
GO:00066505	Esophagus	ESCC	glycerophospholipid metabolic process	174/8552	306/18723	4.92e-05	3.85e-04	174
GO:00065757	Esophagus	ESCC	cellular modified amino acid metabolic process	112/8552	188/18723	8.31e-05	6.06e-04	112

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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

SERINC2

SNV

Missense_Mutation

rs201000290

c.514N>A

p.Gly172Ser

p.G172S

Q96SA4

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-AR-A1AY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unspecific

Doxorubicin

SERINC2

SNV

Missense_Mutation

rs148699108

c.1381N>T

p.Arg461Cys

p.R461C

Q96SA4

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

SERINC2

insertion

Frame_Shift_Ins

novel

c.339_340insCGTGGGCATCACCGTAGGTGCCTTATACACATTTTAGTGT

p.Ala114ArgfsTer45

p.A114Rfs*45

Q96SA4

protein_coding

TCGA-A2-A0D2-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SERINC2

insertion

Frame_Shift_Ins

novel

c.206_207insTGGATATATAT

p.Val70GlyfsTer62

p.V70Gfs*62

Q96SA4

protein_coding

TCGA-BH-A0H7-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

SERINC2

insertion

Frame_Shift_Ins

novel

c.207_208insCAGAA

p.Val70GlnfsTer60

p.V70Qfs*60

Q96SA4

protein_coding

TCGA-BH-A0H7-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

SERINC2

SNV

Missense_Mutation

novel

c.839C>T

p.Ala280Val

p.A280V

Q96SA4

protein_coding

deleterious(0.01)

probably_damaging(0.98)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SERINC2

SNV

Missense_Mutation

rs374319929

c.623G>A

p.Arg208His

p.R208H

Q96SA4

protein_coding

deleterious(0.01)

probably_damaging(0.954)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SERINC2

SNV

Missense_Mutation

novel

c.354N>G

p.Phe118Leu

p.F118L

Q96SA4

protein_coding

tolerated(0.41)

benign(0.035)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SERINC2

SNV

Missense_Mutation

c.856T>C

p.Tyr286His

p.Y286H

Q96SA4

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A6-2686-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

SERINC2

SNV

Missense_Mutation

rs782371695

c.307N>C

p.Tyr103His

p.Y103H

Q96SA4

protein_coding

tolerated(0.28)

benign(0.25)

TCGA-AA-3877-01

Colorectum

colon adenocarcinoma

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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