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: STYX

Gene summary for STYX

Gene summary.

Gene information	Species	Human
	Gene symbol	STYX
	Gene ID	6815
	Gene name	serine/threonine/tyrosine interacting protein
	Gene Alias	STYX
	Cytomap	14q22.1
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	A0A024R641

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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
6815	STYX	LZE4T	Human	Esophagus	ESCC	7.73e-12	3.53e-01	0.0811
6815	STYX	LZE5T	Human	Esophagus	ESCC	1.29e-03	2.18e-01	0.0514
6815	STYX	LZE20T	Human	Esophagus	ESCC	3.86e-05	1.46e-01	0.0662
6815	STYX	LZE22T	Human	Esophagus	ESCC	1.92e-04	1.90e-01	0.068
6815	STYX	LZE24T	Human	Esophagus	ESCC	4.58e-14	2.68e-01	0.0596
6815	STYX	LZE21T	Human	Esophagus	ESCC	1.00e-02	1.20e-01	0.0655
6815	STYX	LZE6T	Human	Esophagus	ESCC	1.05e-02	1.10e-01	0.0845
6815	STYX	P1T-E	Human	Esophagus	ESCC	2.69e-02	8.34e-02	0.0875
6815	STYX	P2T-E	Human	Esophagus	ESCC	2.89e-10	1.41e-01	0.1177
6815	STYX	P4T-E	Human	Esophagus	ESCC	1.17e-18	3.30e-01	0.1323
6815	STYX	P5T-E	Human	Esophagus	ESCC	1.60e-15	1.63e-01	0.1327
6815	STYX	P8T-E	Human	Esophagus	ESCC	3.67e-09	1.47e-01	0.0889
6815	STYX	P9T-E	Human	Esophagus	ESCC	5.85e-08	1.00e-01	0.1131
6815	STYX	P10T-E	Human	Esophagus	ESCC	4.74e-08	1.82e-01	0.116
6815	STYX	P11T-E	Human	Esophagus	ESCC	1.78e-11	2.87e-01	0.1426
6815	STYX	P12T-E	Human	Esophagus	ESCC	2.40e-12	2.37e-01	0.1122
6815	STYX	P15T-E	Human	Esophagus	ESCC	5.74e-25	3.72e-01	0.1149
6815	STYX	P16T-E	Human	Esophagus	ESCC	1.10e-08	1.08e-01	0.1153
6815	STYX	P17T-E	Human	Esophagus	ESCC	8.48e-05	1.44e-01	0.1278
6815	STYX	P20T-E	Human	Esophagus	ESCC	4.53e-12	2.11e-01	0.1124

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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

∗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:009719327	Esophagus	HGIN	intrinsic apoptotic signaling pathway	90/2587	288/18723	1.50e-14	2.80e-12	90
GO:200124227	Esophagus	HGIN	regulation of intrinsic apoptotic signaling pathway	58/2587	164/18723	2.57e-12	3.58e-10	58
GO:200123327	Esophagus	HGIN	regulation of apoptotic signaling pathway	97/2587	356/18723	1.36e-11	1.57e-09	97
GO:200124410	Esophagus	HGIN	positive regulation of intrinsic apoptotic signaling pathway	25/2587	58/18723	4.91e-08	2.75e-06	25
GO:200123519	Esophagus	HGIN	positive regulation of apoptotic signaling pathway	41/2587	126/18723	6.06e-08	3.22e-06	41
GO:001063920	Esophagus	HGIN	negative regulation of organelle organization	79/2587	348/18723	4.12e-06	1.37e-04	79
GO:19021156	Esophagus	HGIN	regulation of organelle assembly	46/2587	186/18723	4.63e-05	1.12e-03	46
GO:004593626	Esophagus	HGIN	negative regulation of phosphate metabolic process	89/2587	441/18723	1.24e-04	2.54e-03	89
GO:001056326	Esophagus	HGIN	negative regulation of phosphorus metabolic process	89/2587	442/18723	1.34e-04	2.71e-03	89
GO:000647017	Esophagus	HGIN	protein dephosphorylation	61/2587	281/18723	1.86e-04	3.51e-03	61
GO:003530425	Esophagus	HGIN	regulation of protein dephosphorylation	24/2587	90/18723	9.27e-04	1.17e-02	24
GO:00340638	Esophagus	HGIN	stress granule assembly	10/2587	26/18723	1.60e-03	1.79e-02	10
GO:19021162	Esophagus	HGIN	negative regulation of organelle assembly	13/2587	41/18723	2.62e-03	2.58e-02	13
GO:005134620	Esophagus	HGIN	negative regulation of hydrolase activity	72/2587	379/18723	2.81e-03	2.75e-02	72
GO:004366619	Esophagus	HGIN	regulation of phosphoprotein phosphatase activity	16/2587	58/18723	4.35e-03	3.84e-02	16
GO:003530320	Esophagus	HGIN	regulation of dephosphorylation	29/2587	128/18723	4.41e-03	3.87e-02	29
GO:0010498111	Esophagus	ESCC	proteasomal protein catabolic process	369/8552	490/18723	1.13e-41	1.80e-38	369
GO:0043161111	Esophagus	ESCC	proteasome-mediated ubiquitin-dependent protein catabolic process	312/8552	412/18723	3.53e-36	4.48e-33	312
GO:0097193111	Esophagus	ESCC	intrinsic apoptotic signaling pathway	222/8552	288/18723	5.87e-28	2.02e-25	222
GO:0006913110	Esophagus	ESCC	nucleocytoplasmic transport	230/8552	301/18723	6.04e-28	2.02e-25	230

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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

STYX

SNV

Missense_Mutation

c.599G>A

p.Gly200Asp

p.G200D

Q8WUJ0

protein_coding

deleterious(0.03)

possibly_damaging(0.832)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

STYX

SNV

Missense_Mutation

c.87N>A

p.Met29Ile

p.M29I

Q8WUJ0

protein_coding

tolerated(0.16)

benign(0.149)

TCGA-C8-A12P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

STYX

SNV

Missense_Mutation

novel

c.451N>G

p.Gln151Glu

p.Q151E

Q8WUJ0

protein_coding

deleterious(0.04)

possibly_damaging(0.729)

TCGA-VS-A9UP-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

STYX

SNV

Missense_Mutation

novel

c.349C>A

p.Leu117Ile

p.L117I

Q8WUJ0

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

STYX

insertion

Frame_Shift_Ins

rs769509399

c.290_291insT

p.Met101TyrfsTer3

p.M101Yfs*3

Q8WUJ0

protein_coding

TCGA-WS-AB45-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

STYX

SNV

Missense_Mutation

novel

c.428N>G

p.Tyr143Cys

p.Y143C

Q8WUJ0

protein_coding

tolerated(0.06)

benign(0.333)

TCGA-AJ-A3EL-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

STYX

SNV

Missense_Mutation

c.80N>A

p.Arg27Gln

p.R27Q

Q8WUJ0

protein_coding

deleterious(0)

possibly_damaging(0.499)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

STYX

SNV

Missense_Mutation

c.289N>T

p.Arg97Cys

p.R97C

Q8WUJ0

protein_coding

tolerated(0.06)

benign(0.031)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

STYX

SNV

Missense_Mutation

novel

c.377N>T

p.Arg126Ile

p.R126I

Q8WUJ0

protein_coding

deleterious(0.02)

probably_damaging(0.987)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

STYX

SNV

Missense_Mutation

c.665N>C

p.Asn222Thr

p.N222T

Q8WUJ0

protein_coding

tolerated_low_confidence(0.08)

benign(0.19)

TCGA-B5-A11E-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<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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