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: SLC35B2

Gene summary for SLC35B2

Gene summary.

Gene information	Species	Human
	Gene symbol	SLC35B2
	Gene ID	347734
	Gene name	solute carrier family 35 member B2
	Gene Alias	PAPST1
	Cytomap	6p21.1
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	Q8TB61

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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
347734	SLC35B2	C57	Human	Oral cavity	OSCC	4.57e-06	4.10e-01	0.1679
347734	SLC35B2	C06	Human	Oral cavity	OSCC	5.70e-14	1.42e+00	0.2699
347734	SLC35B2	C07	Human	Oral cavity	OSCC	1.90e-02	8.76e-01	0.2491
347734	SLC35B2	C08	Human	Oral cavity	OSCC	2.23e-50	9.80e-01	0.1919
347734	SLC35B2	C09	Human	Oral cavity	OSCC	4.48e-13	5.29e-01	0.1431
347734	SLC35B2	LN22	Human	Oral cavity	OSCC	2.70e-02	6.10e-01	0.1733
347734	SLC35B2	LN38	Human	Oral cavity	OSCC	1.35e-06	1.17e+00	0.168
347734	SLC35B2	LN46	Human	Oral cavity	OSCC	7.61e-11	6.70e-01	0.1666
347734	SLC35B2	LP15	Human	Oral cavity	LP	1.16e-14	1.68e+00	0.2174
347734	SLC35B2	LP17	Human	Oral cavity	LP	4.40e-04	6.84e-01	0.2349
347734	SLC35B2	SYSMH1	Human	Oral cavity	OSCC	3.03e-07	2.50e-01	0.1127
347734	SLC35B2	SYSMH2	Human	Oral cavity	OSCC	1.34e-06	2.88e-01	0.2326
347734	SLC35B2	SYSMH3	Human	Oral cavity	OSCC	7.39e-14	4.31e-01	0.2442
347734	SLC35B2	SYSMH6	Human	Oral cavity	OSCC	3.70e-05	2.92e-01	0.1275
347734	SLC35B2	P5_S10_cSCC	Human	Skin	cSCC	2.86e-02	1.93e-02	-0.299
347734	SLC35B2	P1_cSCC	Human	Skin	cSCC	1.67e-17	6.69e-01	0.0292
347734	SLC35B2	P2_cSCC	Human	Skin	cSCC	1.28e-10	3.77e-01	-0.024
347734	SLC35B2	P4_cSCC	Human	Skin	cSCC	7.50e-11	3.66e-01	-0.00290000000000005
347734	SLC35B2	P10_cSCC	Human	Skin	cSCC	4.66e-21	7.67e-01	0.1017
347734	SLC35B2	cSCC_p9	Human	Skin	cSCC	4.24e-03	5.21e-02	-0.1991

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0009150	Colorectum	AD	purine ribonucleotide metabolic process	142/3918	368/18723	4.29e-15	1.17e-12	142
GO:0006163	Colorectum	AD	purine nucleotide metabolic process	149/3918	396/18723	1.08e-14	2.80e-12	149
GO:0072521	Colorectum	AD	purine-containing compound metabolic process	153/3918	416/18723	4.34e-14	1.01e-11	153
GO:0009259	Colorectum	AD	ribonucleotide metabolic process	144/3918	385/18723	5.25e-14	1.13e-11	144
GO:0019693	Colorectum	AD	ribose phosphate metabolic process	145/3918	396/18723	3.01e-13	5.71e-11	145
GO:0009117	Colorectum	AD	nucleotide metabolic process	168/3918	489/18723	2.20e-12	3.36e-10	168
GO:0006753	Colorectum	AD	nucleoside phosphate metabolic process	169/3918	497/18723	4.99e-12	6.98e-10	169
GO:0009152	Colorectum	AD	purine ribonucleotide biosynthetic process	64/3918	169/18723	3.09e-07	1.22e-05	64
GO:0009260	Colorectum	AD	ribonucleotide biosynthetic process	66/3918	182/18723	1.25e-06	4.02e-05	66
GO:0046390	Colorectum	AD	ribose phosphate biosynthetic process	67/3918	190/18723	3.21e-06	9.05e-05	67
GO:0006164	Colorectum	AD	purine nucleotide biosynthetic process	66/3918	191/18723	8.22e-06	1.97e-04	66
GO:0072522	Colorectum	AD	purine-containing compound biosynthetic process	68/3918	200/18723	1.12e-05	2.55e-04	68
GO:0015931	Colorectum	AD	nucleobase-containing compound transport	73/3918	222/18723	2.02e-05	4.10e-04	73
GO:1901293	Colorectum	AD	nucleoside phosphate biosynthetic process	80/3918	256/18723	6.31e-05	1.05e-03	80
GO:0006790	Colorectum	AD	sulfur compound metabolic process	101/3918	339/18723	6.46e-05	1.07e-03	101
GO:0009165	Colorectum	AD	nucleotide biosynthetic process	79/3918	254/18723	8.33e-05	1.30e-03	79
GO:0043123	Colorectum	AD	positive regulation of I-kappaB kinase/NF-kappaB signaling	60/3918	186/18723	1.91e-04	2.56e-03	60
GO:0043122	Colorectum	AD	regulation of I-kappaB kinase/NF-kappaB signaling	76/3918	249/18723	2.17e-04	2.85e-03	76
GO:0007249	Colorectum	AD	I-kappaB kinase/NF-kappaB signaling	82/3918	281/18723	6.09e-04	6.40e-03	82
GO:0033865	Colorectum	AD	nucleoside bisphosphate metabolic process	42/3918	128/18723	1.12e-03	1.02e-02	42

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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

SLC35B2

SNV

Missense_Mutation

rs762279662

c.1232C>T

p.Ala411Val

p.A411V

Q8TB61

protein_coding

tolerated(0.11)

probably_damaging(0.999)

TCGA-A8-A08L-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

SLC35B2

SNV

Missense_Mutation

c.707N>C

p.Glu236Ala

p.E236A

Q8TB61

protein_coding

deleterious(0.01)

possibly_damaging(0.837)

TCGA-BH-A0E7-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SLC35B2

SNV

Missense_Mutation

rs752687684

c.241N>A

p.Val81Met

p.V81M

Q8TB61

protein_coding

deleterious(0.01)

possibly_damaging(0.887)

TCGA-C8-A275-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SLC35B2

SNV

Missense_Mutation

c.263C>A

p.Ala88Asp

p.A88D

Q8TB61

protein_coding

tolerated(0.47)

benign(0.005)

TCGA-D8-A140-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin+cyclophosphamid

SLC35B2

SNV

Missense_Mutation

c.474G>A

p.Met158Ile

p.M158I

Q8TB61

protein_coding

tolerated(0.3)

benign(0.115)

TCGA-E2-A159-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

SLC35B2

SNV

Missense_Mutation

rs772679565

c.290G>A

p.Arg97Gln

p.R97Q

Q8TB61

protein_coding

tolerated(0.27)

benign(0.034)

TCGA-PE-A5DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

SLC35B2

insertion

Frame_Shift_Ins

novel

c.754_755insGATA

p.Met252ArgfsTer32

p.M252Rfs*32

Q8TB61

protein_coding

TCGA-AO-A0J5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate

zoledronic

SLC35B2

insertion

In_Frame_Ins

novel

c.752_753insGATGCCCTGTTTGCCTATAAGATGTCATCGGTG

p.Ser251delinsArgMetProCysLeuProIleArgCysHisArgCys

p.S251delinsRMPCLPIRCHRC

Q8TB61

protein_coding

TCGA-AO-A0J5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate

zoledronic

SLC35B2

deletion

Frame_Shift_Del

novel

c.999delN

p.His334ThrfsTer38

p.H334Tfs*38

Q8TB61

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

SLC35B2

SNV

Missense_Mutation

rs138499828

c.1252N>T

p.Arg418Trp

p.R418W

Q8TB61

protein_coding

deleterious(0.03)

possibly_damaging(0.803)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

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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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