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: ZWINT

Gene summary for ZWINT

Gene summary.

Gene information	Species	Human
	Gene symbol	ZWINT
	Gene ID	11130
	Gene name	ZW10 interacting kinetochore protein
	Gene Alias	HZwint-1
	Cytomap	10q21.1
	Gene Type	protein-coding
	GO ID	GO:0000070
	UniProtAcc	O95229

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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
11130	ZWINT	LZE5T	Human	Esophagus	ESCC	1.57e-02	3.52e-01	0.0514
11130	ZWINT	LZE7T	Human	Esophagus	ESCC	1.02e-03	2.73e-01	0.0667
11130	ZWINT	LZE21T	Human	Esophagus	ESCC	1.16e-05	2.66e-01	0.0655
11130	ZWINT	LZE6T	Human	Esophagus	ESCC	5.35e-04	2.56e-01	0.0845
11130	ZWINT	P1T-E	Human	Esophagus	ESCC	4.62e-03	2.49e-01	0.0875
11130	ZWINT	P2T-E	Human	Esophagus	ESCC	3.73e-18	5.64e-01	0.1177
11130	ZWINT	P4T-E	Human	Esophagus	ESCC	4.13e-17	4.16e-01	0.1323
11130	ZWINT	P5T-E	Human	Esophagus	ESCC	1.81e-22	6.06e-01	0.1327
11130	ZWINT	P8T-E	Human	Esophagus	ESCC	7.33e-10	4.32e-01	0.0889
11130	ZWINT	P9T-E	Human	Esophagus	ESCC	4.01e-04	1.78e-01	0.1131
11130	ZWINT	P10T-E	Human	Esophagus	ESCC	1.14e-05	2.74e-01	0.116
11130	ZWINT	P11T-E	Human	Esophagus	ESCC	9.07e-04	2.70e-01	0.1426
11130	ZWINT	P15T-E	Human	Esophagus	ESCC	5.37e-05	2.09e-01	0.1149
11130	ZWINT	P16T-E	Human	Esophagus	ESCC	7.38e-11	4.36e-01	0.1153
11130	ZWINT	P17T-E	Human	Esophagus	ESCC	2.60e-06	3.04e-01	0.1278
11130	ZWINT	P21T-E	Human	Esophagus	ESCC	6.36e-12	5.68e-01	0.1617
11130	ZWINT	P24T-E	Human	Esophagus	ESCC	4.42e-13	3.16e-01	0.1287
11130	ZWINT	P26T-E	Human	Esophagus	ESCC	6.70e-08	4.08e-01	0.1276
11130	ZWINT	P27T-E	Human	Esophagus	ESCC	1.34e-11	3.80e-01	0.1055
11130	ZWINT	P28T-E	Human	Esophagus	ESCC	3.08e-07	2.17e-01	0.1149

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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
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:190198714	Skin	cSCC	regulation of cell cycle phase transition	150/4864	390/18723	3.21e-08	8.61e-07	150
GO:00070884	Skin	cSCC	regulation of mitotic nuclear division	55/4864	110/18723	5.62e-08	1.44e-06	55
GO:00513063	Skin	cSCC	mitotic sister chromatid separation	38/4864	67/18723	9.27e-08	2.22e-06	38
GO:00447843	Skin	cSCC	metaphase/anaphase transition of cell cycle	37/4864	65/18723	1.20e-07	2.79e-06	37
GO:19020993	Skin	cSCC	regulation of metaphase/anaphase transition of cell cycle	36/4864	63/18723	1.55e-07	3.51e-06	36
GO:00517832	Skin	cSCC	regulation of nuclear division	64/4864	139/18723	2.49e-07	5.25e-06	64
GO:20012514	Skin	cSCC	negative regulation of chromosome organization	43/4864	86/18723	1.53e-06	2.61e-05	43
GO:190199114	Skin	cSCC	negative regulation of mitotic cell cycle phase transition	75/4864	179/18723	2.38e-06	3.84e-05	75
GO:00330473	Skin	cSCC	regulation of mitotic sister chromatid segregation	27/4864	46/18723	2.71e-06	4.30e-05	27
GO:004593014	Skin	cSCC	negative regulation of mitotic cell cycle	93/4864	235/18723	3.14e-06	4.89e-05	93
GO:004578613	Skin	cSCC	negative regulation of cell cycle	140/4864	385/18723	3.64e-06	5.50e-05	140
GO:00458394	Skin	cSCC	negative regulation of mitotic nuclear division	27/4864	48/18723	8.24e-06	1.10e-04	27
GO:00517844	Skin	cSCC	negative regulation of nuclear division	30/4864	56/18723	9.93e-06	1.30e-04	30
GO:00513043	Skin	cSCC	chromosome separation	44/4864	96/18723	2.05e-05	2.40e-04	44
GO:00458413	Skin	cSCC	negative regulation of mitotic metaphase/anaphase transition	23/4864	40/18723	2.37e-05	2.72e-04	23
GO:190198812	Skin	cSCC	negative regulation of cell cycle phase transition	94/4864	249/18723	2.65e-05	3.00e-04	94
GO:001094812	Skin	cSCC	negative regulation of cell cycle process	108/4864	294/18723	2.75e-05	3.09e-04	108
GO:00070943	Skin	cSCC	mitotic spindle assembly checkpoint	22/4864	38/18723	3.07e-05	3.40e-04	22
GO:00711733	Skin	cSCC	spindle assembly checkpoint	22/4864	38/18723	3.07e-05	3.40e-04	22
GO:00711743	Skin	cSCC	mitotic spindle checkpoint	22/4864	38/18723	3.07e-05	3.40e-04	22

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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

ZWINT

SNV

Missense_Mutation

c.452N>A

p.Ala151Glu

p.A151E

O95229

protein_coding

tolerated(0.32)

benign(0.003)

TCGA-A8-A094-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ZWINT

SNV

Missense_Mutation

novel

c.773A>G

p.Asp258Gly

p.D258G

O95229

protein_coding

deleterious_low_confidence(0.01)

benign(0.217)

TCGA-B6-A0RE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ZWINT

SNV

Missense_Mutation

rs758501648

c.52N>A

p.Glu18Lys

p.E18K

O95229

protein_coding

tolerated(0.29)

benign(0.006)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

ZWINT

SNV

Missense_Mutation

c.556N>C

p.Asp186His

p.D186H

O95229

protein_coding

deleterious(0)

possibly_damaging(0.471)

TCGA-E2-A1IN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

ZWINT

SNV

Missense_Mutation

novel

c.266C>A

p.Ala89Glu

p.A89E

O95229

protein_coding

deleterious(0.01)

probably_damaging(0.944)

TCGA-E9-A295-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

ZWINT

insertion

Nonsense_Mutation

novel

c.326_327insTTGGTCTTTCTCCCTTGCTTATCTGTAGAAACAAATG

p.Ile110TrpfsTer9

p.I110Wfs*9

O95229

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

ZWINT

insertion

Frame_Shift_Ins

novel

c.589_590insCTGGTTTACCTCTCTCTGCATCTGAGCTCTGCTC

p.Gln197ProfsTer37

p.Q197Pfs*37

O95229

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

ZWINT

insertion

In_Frame_Ins

novel

c.697_698insTCA

p.Glu233delinsValLys

p.E233delinsVK

O95229

protein_coding

TCGA-A8-A09D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ZWINT

insertion

Nonsense_Mutation

novel

c.696_697insCATTTGTCTTTATGATTTTCTAGTTGT

p.Ala232_Glu233insHisLeuSerLeuTerPheSerSerCys

p.A232_E233insHLSL*FSSC

O95229

protein_coding

TCGA-A8-A09D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ZWINT

SNV

Missense_Mutation

c.757N>A

p.Asp253Asn

p.D253N

O95229

protein_coding

deleterious_low_confidence(0.02)

benign(0.066)

TCGA-FU-A5XV-01

Cervix

cervical & endocervical cancer

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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