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: SERF2

Gene summary for SERF2

Gene summary.

Gene information	Species	Human
	Gene symbol	SERF2
	Gene ID	10169
	Gene name	small EDRK-rich factor 2
	Gene Alias	4F5REL
	Cytomap	15q15.3
	Gene Type	protein-coding
	GO ID	GO:0008150
	UniProtAcc	P84101

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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
10169	SERF2	GSM4909277	Human	Breast	Precancer	1.07e-02	-6.04e-01	0.0177
10169	SERF2	GSM4909280	Human	Breast	Precancer	2.13e-03	-4.73e-01	0.0305
10169	SERF2	GSM4909281	Human	Breast	IDC	5.87e-14	-2.33e-01	0.21
10169	SERF2	GSM4909282	Human	Breast	IDC	3.77e-47	3.29e-01	-0.0288
10169	SERF2	GSM4909286	Human	Breast	IDC	2.90e-47	-3.57e-01	0.1081
10169	SERF2	GSM4909289	Human	Breast	IDC	2.25e-03	2.49e-01	0.1064
10169	SERF2	GSM4909290	Human	Breast	IDC	2.32e-82	4.89e-01	0.2096
10169	SERF2	GSM4909291	Human	Breast	IDC	2.11e-07	2.11e-01	0.1753
10169	SERF2	GSM4909294	Human	Breast	IDC	7.52e-32	2.37e-01	0.2022
10169	SERF2	GSM4909296	Human	Breast	IDC	1.41e-35	3.02e-01	0.1524
10169	SERF2	GSM4909297	Human	Breast	IDC	1.21e-05	-1.23e-01	0.1517
10169	SERF2	GSM4909301	Human	Breast	IDC	5.22e-87	4.39e-01	0.1577
10169	SERF2	GSM4909302	Human	Breast	IDC	2.79e-12	1.39e-01	0.1545
10169	SERF2	GSM4909304	Human	Breast	IDC	1.57e-55	3.69e-01	0.1636
10169	SERF2	GSM4909305	Human	Breast	IDC	8.26e-04	-1.30e-01	0.0436
10169	SERF2	GSM4909307	Human	Breast	IDC	5.87e-11	1.66e-01	0.1569
10169	SERF2	GSM4909308	Human	Breast	IDC	2.26e-16	2.16e-01	0.158
10169	SERF2	GSM4909309	Human	Breast	IDC	1.75e-04	1.21e-01	0.0483
10169	SERF2	GSM4909311	Human	Breast	IDC	1.20e-23	-1.18e-01	0.1534
10169	SERF2	GSM4909313	Human	Breast	IDC	1.36e-06	1.48e-01	0.0391

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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:00316481	Liver	Cirrhotic	protein destabilization	20/4634	46/18723	4.15e-03	2.22e-02	20
GO:003164722	Liver	HCC	regulation of protein stability	211/7958	298/18723	2.29e-23	5.01e-21	211
GO:00316482	Liver	HCC	protein destabilization	29/7958	46/18723	3.95e-03	1.74e-02	29
GO:003164732	Liver	Cyst	regulation of protein stability	21/496	298/18723	4.94e-05	2.67e-03	21
GO:00316478	Lung	IAC	regulation of protein stability	62/2061	298/18723	5.37e-07	3.32e-05	62
GO:00316483	Lung	IAC	protein destabilization	15/2061	46/18723	7.40e-05	1.55e-03	15
GO:003164713	Lung	AIS	regulation of protein stability	62/1849	298/18723	1.06e-08	1.63e-06	62
GO:003164811	Lung	AIS	protein destabilization	13/1849	46/18723	3.66e-04	6.46e-03	13
GO:003164723	Lung	MIAC	regulation of protein stability	36/967	298/18723	1.93e-06	2.42e-04	36
GO:003164720	Oral cavity	OSCC	regulation of protein stability	193/7305	298/18723	1.30e-19	1.95e-17	193
GO:00316485	Oral cavity	OSCC	protein destabilization	29/7305	46/18723	8.26e-04	4.38e-03	29
GO:0031647110	Oral cavity	LP	regulation of protein stability	132/4623	298/18723	8.16e-14	7.99e-12	132
GO:003164726	Oral cavity	EOLP	regulation of protein stability	75/2218	298/18723	1.22e-10	1.35e-08	75
GO:003164733	Oral cavity	NEOLP	regulation of protein stability	73/2005	298/18723	7.46e-12	1.17e-09	73
GO:003164718	Prostate	BPH	regulation of protein stability	111/3107	298/18723	4.58e-18	1.42e-15	111
GO:003164719	Prostate	Tumor	regulation of protein stability	112/3246	298/18723	4.18e-17	1.18e-14	112
GO:003164728	Skin	AK	regulation of protein stability	64/1910	298/18723	5.93e-09	4.14e-07	64
GO:0031647112	Skin	SCCIS	regulation of protein stability	26/919	298/18723	3.35e-03	3.00e-02	26
GO:003164729	Skin	cSCC	regulation of protein stability	144/4864	298/18723	6.51e-17	6.80e-15	144
GO:003164730	Thyroid	HT	regulation of protein stability	57/1272	298/18723	8.04e-13	1.79e-10	57

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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

SERF2

SNV

Missense_Mutation

c.241C>G

p.Leu81Val

p.L81V

P84101

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.672)

TCGA-AN-A0AJ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SERF2

SNV

Missense_Mutation

c.475N>G

p.Gln159Glu

p.Q159E

P84101

protein_coding

deleterious_low_confidence(0)

benign(0.125)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SERF2

SNV

Missense_Mutation

c.136A>C

p.Asn46His

p.N46H

P84101

protein_coding

tolerated_low_confidence(1)

benign(0)

TCGA-AA-3977-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

SERF2

SNV

Missense_Mutation

c.352N>G

p.Cys118Gly

p.C118G

P84101

protein_coding

deleterious_low_confidence(0.02)

benign(0.014)

TCGA-AA-A02R-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

SERF2

SNV

Missense_Mutation

c.473C>A

p.Pro158His

p.P158H

P84101

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.996)

TCGA-CK-6746-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

SERF2

SNV

Missense_Mutation

novel

c.260N>T

p.Arg87Ile

p.R87I

P84101

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.852)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

SERF2

SNV

Missense_Mutation

novel

c.418N>A

p.Asp140Asn

p.D140N

P84101

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.978)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SERF2

SNV

Missense_Mutation

novel

c.165N>G

p.His55Gln

p.H55Q

P84101

protein_coding

deleterious_low_confidence(0)

benign(0.036)

TCGA-S2-AA1A-01

Lung

lung adenocarcinoma

Female

>=65

I/II

Unknown

SERF2

SNV

Missense_Mutation

c.101N>T

p.Ala34Val

p.A34V

P84101

protein_coding

deleterious_low_confidence(0.02)

probably_damaging(0.992)

TCGA-34-A5IX-01

Lung

lung squamous cell carcinoma

Male

>=65

I/II

Unknown

SERF2

SNV

Missense_Mutation

novel

c.388N>T

p.Pro130Ser

p.P130S

P84101

protein_coding

tolerated_low_confidence(0.54)

benign(0.001)

TCGA-90-A4ED-01

Lung

lung squamous cell carcinoma

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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