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: SEPT2

Gene summary for SEPT2

Gene summary.

Gene information	Species	Human
	Gene symbol	SEPT2
	Gene ID	4735
	Gene name	septin 2
	Gene Alias	DIFF6
	Cytomap	2q37.3
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q15019

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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
4735	SEPT2	P130T-E	Human	Esophagus	ESCC	3.64e-67	1.98e+00	0.1676
4735	SEPT2	S41	Human	Liver	Cirrhotic	1.47e-02	-4.63e-01	-0.0343
4735	SEPT2	S43	Human	Liver	Cirrhotic	1.78e-25	-4.63e-01	-0.0187
4735	SEPT2	HCC1_Meng	Human	Liver	HCC	9.30e-39	-2.64e-01	0.0246
4735	SEPT2	HCC2_Meng	Human	Liver	HCC	2.28e-27	3.48e-03	0.0107
4735	SEPT2	cirrhotic1	Human	Liver	Cirrhotic	2.96e-05	-3.64e-02	0.0202
4735	SEPT2	cirrhotic2	Human	Liver	Cirrhotic	1.70e-10	2.21e-01	0.0201
4735	SEPT2	cirrhotic3	Human	Liver	Cirrhotic	2.45e-06	3.90e-02	0.0215
4735	SEPT2	p6	Human	Liver	Cyst	1.47e-02	-4.63e-01	-0.0218
4735	SEPT2	HCC1	Human	Liver	HCC	5.25e-04	-4.63e-01	0.5336
4735	SEPT2	HCC2	Human	Liver	HCC	3.51e-06	-4.63e-01	0.5341
4735	SEPT2	HCC5	Human	Liver	HCC	2.08e-09	-4.63e-01	0.4932
4735	SEPT2	Pt13.b	Human	Liver	HCC	1.09e-13	9.83e-02	0.0251
4735	SEPT2	Pt14.a	Human	Liver	HCC	5.86e-05	2.10e-01	0.0169
4735	SEPT2	S014	Human	Liver	HCC	6.57e-20	1.22e+00	0.2254
4735	SEPT2	S015	Human	Liver	HCC	1.29e-23	1.59e+00	0.2375
4735	SEPT2	S016	Human	Liver	HCC	9.92e-28	1.50e+00	0.2243
4735	SEPT2	S027	Human	Liver	HCC	3.59e-04	8.49e-01	0.2446
4735	SEPT2	S028	Human	Liver	HCC	1.79e-16	1.19e+00	0.2503
4735	SEPT2	S029	Human	Liver	HCC	3.13e-08	8.66e-01	0.2581

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0513120	Cervix	CC	Shigellosis	69/1267	247/8465	7.64e-08	1.03e-06	6.10e-07	69
hsa0510020	Cervix	CC	Bacterial invasion of epithelial cells	23/1267	77/8465	6.25e-04	2.93e-03	1.73e-03	23
hsa05131110	Cervix	CC	Shigellosis	69/1267	247/8465	7.64e-08	1.03e-06	6.10e-07	69
hsa05100110	Cervix	CC	Bacterial invasion of epithelial cells	23/1267	77/8465	6.25e-04	2.93e-03	1.73e-03	23
hsa0513125	Cervix	HSIL_HPV	Shigellosis	27/459	247/8465	3.78e-04	3.49e-03	2.82e-03	27
hsa0513135	Cervix	HSIL_HPV	Shigellosis	27/459	247/8465	3.78e-04	3.49e-03	2.82e-03	27
hsa0513145	Cervix	N_HPV	Shigellosis	23/349	247/8465	2.10e-04	1.75e-03	1.37e-03	23
hsa0510025	Cervix	N_HPV	Bacterial invasion of epithelial cells	10/349	77/8465	1.17e-03	7.93e-03	6.20e-03	10
hsa0513155	Cervix	N_HPV	Shigellosis	23/349	247/8465	2.10e-04	1.75e-03	1.37e-03	23
hsa0510035	Cervix	N_HPV	Bacterial invasion of epithelial cells	10/349	77/8465	1.17e-03	7.93e-03	6.20e-03	10
hsa05131	Colorectum	AD	Shigellosis	109/2092	247/8465	1.09e-11	2.44e-10	1.55e-10	109
hsa05100	Colorectum	AD	Bacterial invasion of epithelial cells	44/2092	77/8465	1.13e-09	2.22e-08	1.42e-08	44
hsa051311	Colorectum	AD	Shigellosis	109/2092	247/8465	1.09e-11	2.44e-10	1.55e-10	109
hsa051001	Colorectum	AD	Bacterial invasion of epithelial cells	44/2092	77/8465	1.13e-09	2.22e-08	1.42e-08	44
hsa051312	Colorectum	SER	Shigellosis	87/1580	247/8465	3.07e-10	7.27e-09	5.28e-09	87
hsa051002	Colorectum	SER	Bacterial invasion of epithelial cells	36/1580	77/8465	1.56e-08	3.45e-07	2.50e-07	36
hsa051313	Colorectum	SER	Shigellosis	87/1580	247/8465	3.07e-10	7.27e-09	5.28e-09	87
hsa051003	Colorectum	SER	Bacterial invasion of epithelial cells	36/1580	77/8465	1.56e-08	3.45e-07	2.50e-07	36
hsa0513126	Endometrium	AEH	Shigellosis	78/1197	247/8465	9.23e-13	2.00e-11	1.46e-11	78
hsa0510026	Endometrium	AEH	Bacterial invasion of epithelial cells	32/1197	77/8465	3.28e-09	5.91e-08	4.33e-08	32

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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

SEPT2

SNV

Missense_Mutation

c.502G>A

p.Glu168Lys

p.E168K

Q15019

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-A8-A09K-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SEPT2

SNV

Missense_Mutation

c.1160N>T

p.Gly387Val

p.G387V

Q15019

protein_coding

tolerated_low_confidence(0.12)

benign(0.073)

TCGA-C8-A278-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

tamoxiphen

SEPT2

SNV

Missense_Mutation

novel

c.362T>C

p.Val121Ala

p.V121A

Q15019

protein_coding

tolerated(0.24)

possibly_damaging(0.757)

TCGA-E2-A574-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SEPT2

SNV

Missense_Mutation

novel

c.110C>T

p.Ser37Phe

p.S37F

Q15019

protein_coding

deleterious(0)

possibly_damaging(0.493)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SEPT2

SNV

Missense_Mutation

novel

c.331N>A

p.Glu111Lys

p.E111K

Q15019

protein_coding

tolerated(1)

benign(0.031)

TCGA-JW-A5VJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SEPT2

SNV

Missense_Mutation

novel

c.551N>A

p.Cys184Tyr

p.C184Y

Q15019

protein_coding

deleterious(0)

probably_damaging(0.964)

TCGA-JW-A5VJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SEPT2

SNV

Missense_Mutation

novel

c.247N>G

p.Leu83Val

p.L83V

Q15019

protein_coding

deleterious(0.01)

probably_damaging(0.981)

TCGA-VS-A958-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SEPT2

insertion

Frame_Shift_Ins

novel

c.201_202insA

p.Gly70ArgfsTer3

p.G70Rfs*3

Q15019

protein_coding

TCGA-C5-A1ML-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SEPT2

SNV

Missense_Mutation

c.427G>A

p.Ala143Thr

p.A143T

Q15019

protein_coding

deleterious(0.04)

possibly_damaging(0.806)

TCGA-AA-3977-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

SEPT2

SNV

Missense_Mutation

c.391N>T

p.Arg131Cys

p.R131C

Q15019

protein_coding

deleterious(0)

possibly_damaging(0.676)

TCGA-AA-A02O-01

Colorectum

colon adenocarcinoma

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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