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: SUN1

Gene summary for SUN1

Gene summary.

Gene information	Species	Human
	Gene symbol	SUN1
	Gene ID	23353
	Gene name	Sad1 and UNC84 domain containing 1
	Gene Alias	UNC84A
	Cytomap	7p22.3
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	O94901

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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
23353	SUN1	LZE2T	Human	Esophagus	ESCC	3.23e-02	3.87e-01	0.082
23353	SUN1	LZE4T	Human	Esophagus	ESCC	7.23e-18	2.31e-01	0.0811
23353	SUN1	LZE5T	Human	Esophagus	ESCC	6.04e-04	3.00e-01	0.0514
23353	SUN1	LZE7T	Human	Esophagus	ESCC	3.79e-04	3.12e-01	0.0667
23353	SUN1	LZE8T	Human	Esophagus	ESCC	1.89e-06	1.35e-01	0.067
23353	SUN1	LZE22D1	Human	Esophagus	HGIN	9.75e-05	1.85e-02	0.0595
23353	SUN1	LZE22T	Human	Esophagus	ESCC	1.62e-06	7.09e-01	0.068
23353	SUN1	LZE24T	Human	Esophagus	ESCC	2.28e-08	2.43e-01	0.0596
23353	SUN1	LZE21T	Human	Esophagus	ESCC	4.20e-05	6.21e-01	0.0655
23353	SUN1	P1T-E	Human	Esophagus	ESCC	1.51e-09	7.25e-01	0.0875
23353	SUN1	P2T-E	Human	Esophagus	ESCC	3.82e-23	3.77e-01	0.1177
23353	SUN1	P4T-E	Human	Esophagus	ESCC	1.51e-18	4.43e-01	0.1323
23353	SUN1	P5T-E	Human	Esophagus	ESCC	2.22e-23	4.10e-01	0.1327
23353	SUN1	P8T-E	Human	Esophagus	ESCC	4.09e-29	6.81e-01	0.0889
23353	SUN1	P9T-E	Human	Esophagus	ESCC	5.10e-19	2.95e-01	0.1131
23353	SUN1	P10T-E	Human	Esophagus	ESCC	1.08e-33	6.92e-01	0.116
23353	SUN1	P11T-E	Human	Esophagus	ESCC	1.05e-09	6.92e-01	0.1426
23353	SUN1	P12T-E	Human	Esophagus	ESCC	2.66e-36	7.89e-01	0.1122
23353	SUN1	P15T-E	Human	Esophagus	ESCC	2.57e-20	5.22e-01	0.1149
23353	SUN1	P16T-E	Human	Esophagus	ESCC	1.25e-22	3.29e-01	0.1153

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:003450417	Esophagus	HGIN	protein localization to nucleus	84/2587	290/18723	1.06e-11	1.24e-09	84
GO:005165616	Esophagus	HGIN	establishment of organelle localization	90/2587	390/18723	4.27e-07	1.94e-05	90
GO:005165126	Esophagus	HGIN	maintenance of location in cell	53/2587	214/18723	1.22e-05	3.45e-04	53
GO:005123520	Esophagus	HGIN	maintenance of location	73/2587	327/18723	1.73e-05	4.71e-04	73
GO:004518523	Esophagus	HGIN	maintenance of protein location	28/2587	94/18723	4.52e-05	1.09e-03	28
GO:00500003	Esophagus	HGIN	chromosome localization	24/2587	82/18723	2.07e-04	3.82e-03	24
GO:00069975	Esophagus	HGIN	nucleus organization	34/2587	133/18723	2.20e-04	4.00e-03	34
GO:003070517	Esophagus	HGIN	cytoskeleton-dependent intracellular transport	45/2587	195/18723	3.07e-04	5.15e-03	45
GO:003250719	Esophagus	HGIN	maintenance of protein location in cell	20/2587	65/18723	3.31e-04	5.48e-03	20
GO:00070593	Esophagus	HGIN	chromosome segregation	71/2587	346/18723	3.47e-04	5.62e-03	71
GO:00513033	Esophagus	HGIN	establishment of chromosome localization	23/2587	80/18723	3.71e-04	5.77e-03	23
GO:00514575	Esophagus	HGIN	maintenance of protein location in nucleus	10/2587	23/18723	5.09e-04	7.38e-03	10
GO:00725959	Esophagus	HGIN	maintenance of protein localization in organelle	14/2587	42/18723	1.05e-03	1.31e-02	14
GO:00109707	Esophagus	HGIN	transport along microtubule	35/2587	155/18723	2.01e-03	2.12e-02	35
GO:00069983	Esophagus	HGIN	nuclear envelope organization	14/2587	47/18723	3.49e-03	3.23e-02	14
GO:000150316	Esophagus	HGIN	ossification	75/2587	408/18723	5.49e-03	4.49e-02	75
GO:005165617	Esophagus	ESCC	establishment of organelle localization	273/8552	390/18723	9.13e-23	1.81e-20	273
GO:003450418	Esophagus	ESCC	protein localization to nucleus	211/8552	290/18723	4.06e-21	6.60e-19	211
GO:000705911	Esophagus	ESCC	chromosome segregation	238/8552	346/18723	1.72e-18	1.82e-16	238
GO:00482853	Esophagus	ESCC	organelle fission	301/8552	488/18723	4.64e-13	2.12e-11	301

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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

SUN1

SNV

Missense_Mutation

c.499N>G

p.Gln167Glu

p.Q167E

O94901

protein_coding

tolerated(0.1)

probably_damaging(0.994)

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SUN1

SNV

Missense_Mutation

c.730N>T

p.Ala244Ser

p.A244S

O94901

protein_coding

tolerated(0.12)

benign(0.104)

TCGA-E9-A1NC-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SUN1

SNV

Missense_Mutation

novel

c.968N>T

p.Trp323Leu

p.W323L

O94901

protein_coding

deleterious(0.05)

probably_damaging(0.997)

TCGA-S3-AA10-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

SUN1

insertion

Nonsense_Mutation

novel

c.216_217insAGTTGTGAATTGTCTGAAGCCTTTAGATAAATTCTAAATTTA

p.Gly72_Ala73insSerCysGluLeuSerGluAlaPheArgTerIleLeuAsnLeu

p.G72_A73insSCELSEAFR*ILNL

O94901

protein_coding

TCGA-B6-A0IC-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SUN1

SNV

Missense_Mutation

novel

c.841C>T

p.Leu281Phe

p.L281F

O94901

protein_coding

tolerated(0.11)

possibly_damaging(0.677)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SUN1

SNV

Missense_Mutation

c.2077N>G

p.Leu693Val

p.L693V

O94901

protein_coding

tolerated(0.2)

benign(0.06)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

SUN1

SNV

Missense_Mutation

rs537139636

c.1702G>A

p.Val568Met

p.V568M

O94901

protein_coding

deleterious(0.04)

benign(0.07)

TCGA-A6-6653-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

SUN1

SNV

Missense_Mutation

rs775225289

c.149G>A

p.Arg50Gln

p.R50Q

O94901

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AA-3492-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

SUN1

SNV

Missense_Mutation

c.1776N>T

p.Glu592Asp

p.E592D

O94901

protein_coding

deleterious(0)

probably_damaging(0.933)

TCGA-AA-3663-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

SUN1

SNV

Missense_Mutation

novel

c.770N>T

p.Ser257Phe

p.S257F

O94901

protein_coding

deleterious(0)

possibly_damaging(0.654)

TCGA-AA-3811-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

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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