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: SHTN1

Gene summary for SHTN1

Gene summary.

Gene information	Species	Human
	Gene symbol	SHTN1
	Gene ID	57698
	Gene name	shootin 1
	Gene Alias	KIAA1598
	Cytomap	10q25.3
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	A0MZ66

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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
57698	SHTN1	C30	Human	Oral cavity	OSCC	7.25e-28	1.04e+00	0.3055
57698	SHTN1	C43	Human	Oral cavity	OSCC	3.01e-02	7.84e-02	0.1704
57698	SHTN1	C51	Human	Oral cavity	OSCC	1.50e-03	3.06e-01	0.2674
57698	SHTN1	C06	Human	Oral cavity	OSCC	4.57e-04	8.69e-01	0.2699
57698	SHTN1	C08	Human	Oral cavity	OSCC	1.52e-11	3.03e-01	0.1919
57698	SHTN1	C09	Human	Oral cavity	OSCC	1.00e-06	2.82e-01	0.1431
57698	SHTN1	SYSMH1	Human	Oral cavity	OSCC	1.84e-05	2.31e-01	0.1127
57698	SHTN1	SYSMH2	Human	Oral cavity	OSCC	4.70e-21	6.78e-01	0.2326
57698	SHTN1	SYSMH3	Human	Oral cavity	OSCC	2.85e-28	6.97e-01	0.2442
57698	SHTN1	SYSMH5	Human	Oral cavity	OSCC	1.27e-07	2.39e-01	0.0647
57698	SHTN1	SYSMH6	Human	Oral cavity	OSCC	3.92e-08	3.34e-01	0.1275
57698	SHTN1	HTA12-15-2	Human	Pancreas	PDAC	2.40e-02	3.62e-01	0.2315
57698	SHTN1	HTA12-26-1	Human	Pancreas	PDAC	1.78e-20	9.54e-01	0.3728
57698	SHTN1	HTA12-29-1	Human	Pancreas	PDAC	6.21e-45	9.25e-01	0.3722
57698	SHTN1	male-WTA	Human	Thyroid	PTC	1.98e-37	2.89e-01	0.1037
57698	SHTN1	PTC01	Human	Thyroid	PTC	1.88e-19	1.56e-01	0.1899
57698	SHTN1	PTC04	Human	Thyroid	PTC	5.20e-19	3.21e-01	0.1927
57698	SHTN1	PTC05	Human	Thyroid	PTC	8.44e-21	8.64e-01	0.2065
57698	SHTN1	PTC06	Human	Thyroid	PTC	3.18e-39	1.05e+00	0.2057
57698	SHTN1	PTC07	Human	Thyroid	PTC	2.60e-44	7.64e-01	0.2044

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:000701510	Cervix	CC	actin filament organization	109/2311	442/18723	4.92e-13	2.45e-10	109
GO:00071639	Cervix	CC	establishment or maintenance of cell polarity	63/2311	218/18723	4.25e-11	8.76e-09	63
GO:00072656	Cervix	CC	Ras protein signal transduction	79/2311	337/18723	9.49e-09	7.77e-07	79
GO:00300108	Cervix	CC	establishment of cell polarity	42/2311	143/18723	4.30e-08	2.62e-06	42
GO:006157210	Cervix	CC	actin filament bundle organization	44/2311	161/18723	2.08e-07	9.34e-06	44
GO:00109757	Cervix	CC	regulation of neuron projection development	88/2311	445/18723	4.26e-06	1.09e-04	88
GO:00107206	Cervix	CC	positive regulation of cell development	64/2311	298/18723	5.69e-06	1.41e-04	64
GO:00313467	Cervix	CC	positive regulation of cell projection organization	72/2311	353/18723	1.04e-05	2.32e-04	72
GO:00160498	Cervix	CC	cell growth	92/2311	482/18723	1.16e-05	2.49e-04	92
GO:00325359	Cervix	CC	regulation of cellular component size	76/2311	383/18723	1.66e-05	3.21e-04	76
GO:00615647	Cervix	CC	axon development	89/2311	467/18723	1.71e-05	3.27e-04	89
GO:00072666	Cervix	CC	Rho protein signal transduction	35/2311	137/18723	1.77e-05	3.33e-04	35
GO:00074097	Cervix	CC	axonogenesis	78/2311	418/18723	1.14e-04	1.43e-03	78
GO:00459277	Cervix	CC	positive regulation of growth	53/2311	259/18723	1.33e-04	1.64e-03	53
GO:00015588	Cervix	CC	regulation of cell growth	77/2311	414/18723	1.40e-04	1.70e-03	77
GO:00303077	Cervix	CC	positive regulation of cell growth	36/2311	166/18723	4.84e-04	4.75e-03	36
GO:00507705	Cervix	CC	regulation of axonogenesis	34/2311	154/18723	4.87e-04	4.76e-03	34
GO:00300487	Cervix	CC	actin filament-based movement	29/2311	127/18723	6.91e-04	6.33e-03	29
GO:20001147	Cervix	CC	regulation of establishment of cell polarity	9/2311	22/18723	7.19e-04	6.49e-03	9
GO:00486386	Cervix	CC	regulation of developmental growth	61/2311	330/18723	7.69e-04	6.85e-03	61

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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

SHTN1

SNV

Missense_Mutation

c.1631C>T

p.Pro544Leu

p.P544L

A0MZ66

protein_coding

deleterious(0)

benign(0.001)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SHTN1

SNV

Missense_Mutation

novel

c.975G>C

p.Gln325His

p.Q325H

A0MZ66

protein_coding

deleterious(0.01)

probably_damaging(0.991)

TCGA-XX-A89A-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SHTN1

insertion

Nonsense_Mutation

novel

c.1034_1035insTTCCATGCTATTCTCATGATAGTGAATCTCATGAGATCTGATG

p.Asn346SerfsTer6

p.N346Sfs*6

A0MZ66

protein_coding

TCGA-AO-A03O-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

SHTN1

insertion

Nonsense_Mutation

novel

c.1031_1032insTTCTCTCTTCCCTGCTGCCATGTAAGATGTGACTTGCTTCTCCTT

p.Arg344_Val345insSerLeuPheProAlaAlaMetTerAspValThrCysPheSerLeu

p.R344_V345insSLFPAAM*DVTCFSL

A0MZ66

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

SHTN1

SNV

Missense_Mutation

novel

c.117C>A

p.Asp39Glu

p.D39E

A0MZ66

protein_coding

tolerated(0.29)

possibly_damaging(0.496)

TCGA-EK-A2PL-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

SHTN1

insertion

In_Frame_Ins

novel

c.465_466insTCTGAAATT

p.Gln155_Glu156insSerGluIle

p.Q155_E156insSEI

A0MZ66

protein_coding

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

SHTN1

SNV

Missense_Mutation

novel

c.443N>A

p.Arg148Gln

p.R148Q

A0MZ66

protein_coding

tolerated(0.6)

benign(0.006)

TCGA-AA-3949-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

SHTN1

SNV

Missense_Mutation

c.1654N>C

p.Ser552Arg

p.S552R

A0MZ66

protein_coding

tolerated(0.11)

benign(0.003)

TCGA-AA-3977-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

SHTN1

SNV

Missense_Mutation

c.716N>C

p.Phe239Ser

p.F239S

A0MZ66

protein_coding

deleterious(0.01)

benign(0.005)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

SHTN1

SNV

Missense_Mutation

novel

c.452N>G

p.Ile151Ser

p.I151S

A0MZ66

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

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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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