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: FSD2

Gene summary for FSD2

Gene summary.

Gene information	Species	Human
	Gene symbol	FSD2
	Gene ID	123722
	Gene name	fibronectin type III and SPRY domain containing 2
	Gene Alias	SPRYD1
	Cytomap	15q25.2
	Gene Type	protein-coding
	GO ID	GO:0005575
	UniProtAcc	A1L4K1

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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
123722	FSD2	HCC1	Human	Liver	HCC	6.31e-22	1.60e+00	0.5336
123722	FSD2	HCC2	Human	Liver	HCC	6.04e-30	2.02e+00	0.5341
123722	FSD2	HCC5	Human	Liver	HCC	4.49e-23	1.51e+00	0.4932

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease

∗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:0071496111	Esophagus	ESCC	cellular response to external stimulus	215/8552	320/18723	4.29e-15	2.43e-13	215
GO:0031668111	Esophagus	ESCC	cellular response to extracellular stimulus	168/8552	246/18723	4.93e-13	2.23e-11	168
GO:0031669110	Esophagus	ESCC	cellular response to nutrient levels	148/8552	215/18723	4.58e-12	1.76e-10	148
GO:0031667111	Esophagus	ESCC	response to nutrient levels	289/8552	474/18723	9.25e-12	3.47e-10	289
GO:0016049110	Esophagus	ESCC	cell growth	289/8552	482/18723	1.29e-10	3.77e-09	289
GO:0009267110	Esophagus	ESCC	cellular response to starvation	110/8552	156/18723	2.63e-10	7.37e-09	110
GO:0009895111	Esophagus	ESCC	negative regulation of catabolic process	201/8552	320/18723	3.88e-10	1.05e-08	201
GO:004259419	Esophagus	ESCC	response to starvation	133/8552	197/18723	4.31e-10	1.14e-08	133
GO:00086544	Esophagus	ESCC	phospholipid biosynthetic process	162/8552	253/18723	2.59e-09	5.73e-08	162
GO:000155819	Esophagus	ESCC	regulation of cell growth	248/8552	414/18723	2.97e-09	6.45e-08	248
GO:0031330111	Esophagus	ESCC	negative regulation of cellular catabolic process	166/8552	262/18723	5.17e-09	1.08e-07	166
GO:00464744	Esophagus	ESCC	glycerophospholipid biosynthetic process	135/8552	211/18723	5.75e-08	1.02e-06	135
GO:00450175	Esophagus	ESCC	glycerolipid biosynthetic process	154/8552	252/18723	5.20e-07	6.96e-06	154
GO:002260420	Esophagus	ESCC	regulation of cell morphogenesis	180/8552	309/18723	5.19e-06	5.45e-05	180
GO:00066446	Esophagus	ESCC	phospholipid metabolic process	218/8552	383/18723	5.37e-06	5.59e-05	218
GO:00193958	Esophagus	ESCC	fatty acid oxidation	69/8552	103/18723	9.95e-06	9.44e-05	69
GO:00344407	Esophagus	ESCC	lipid oxidation	71/8552	108/18723	2.00e-05	1.74e-04	71
GO:00090628	Esophagus	ESCC	fatty acid catabolic process	66/8552	100/18723	3.21e-05	2.66e-04	66
GO:00066318	Esophagus	ESCC	fatty acid metabolic process	217/8552	390/18723	4.21e-05	3.39e-04	217
GO:00066561	Esophagus	ESCC	phosphatidylcholine biosynthetic process	24/8552	29/18723	4.50e-05	3.55e-04	24

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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

FSD2

SNV

Missense_Mutation

rs200109394

c.1411N>T

p.Pro471Ser

p.P471S

A1L4K1

protein_coding

deleterious(0.04)

probably_damaging(1)

TCGA-A7-A26E-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

FSD2

SNV

Missense_Mutation

c.413N>T

p.Gly138Val

p.G138V

A1L4K1

protein_coding

deleterious(0.04)

benign(0.348)

TCGA-AN-A0AM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

FSD2

SNV

Missense_Mutation

rs774888742

c.1499N>T

p.Ser500Leu

p.S500L

A1L4K1

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-D8-A142-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyclophosphamid

FSD2

SNV

Missense_Mutation

c.923C>A

p.Thr308Lys

p.T308K

A1L4K1

protein_coding

deleterious(0.01)

benign(0.435)

TCGA-D8-A1X9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

adriamycin+cyclophosphamide

FSD2

SNV

Missense_Mutation

rs781225191

c.388G>A

p.Glu130Lys

p.E130K

A1L4K1

protein_coding

tolerated(0.07)

benign(0.096)

TCGA-DS-A0VK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

FSD2

SNV

Missense_Mutation

novel

c.493N>T

p.Val165Phe

p.V165F

A1L4K1

protein_coding

deleterious(0)

probably_damaging(0.957)

TCGA-DS-A1OC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

gemcitabine

FSD2

SNV

Missense_Mutation

c.520N>A

p.Glu174Lys

p.E174K

A1L4K1

protein_coding

tolerated(0.07)

possibly_damaging(0.867)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

FSD2

SNV

Missense_Mutation

c.1398G>A

p.Met466Ile

p.M466I

A1L4K1

protein_coding

tolerated(0.05)

benign(0.003)

TCGA-LP-A4AV-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

FSD2

SNV

Missense_Mutation

c.88G>A

p.Glu30Lys

p.E30K

A1L4K1

protein_coding

tolerated(0.41)

benign(0.006)

TCGA-VS-A8QC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

paclitaxel

FSD2

SNV

Missense_Mutation

novel

c.586N>A

p.Glu196Lys

p.E196K

A1L4K1

protein_coding

deleterious(0.04)

benign(0.157)

TCGA-ZJ-AAXU-01

Cervix

cervical & endocervical cancer

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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