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: SLA

Gene summary for SLA

Gene summary.

Gene information	Species	Human
	Gene symbol	SLA
	Gene ID	6503
	Gene name	Src like adaptor
	Gene Alias	SLA1
	Cytomap	8q24.22
	Gene Type	protein-coding
	GO ID	GO:0002376
	UniProtAcc	Q13239

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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
6503	SLA	PTC01	Human	Thyroid	PTC	1.01e-03	1.11e-01	0.1899
6503	SLA	PTC04	Human	Thyroid	PTC	5.58e-07	2.35e-01	0.1927
6503	SLA	PTC06	Human	Thyroid	PTC	2.86e-17	5.34e-01	0.2057
6503	SLA	PTC07	Human	Thyroid	PTC	2.19e-11	3.25e-01	0.2044

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:004325420	Oral cavity	OSCC	regulation of protein-containing complex assembly	255/7305	428/18723	2.94e-18	3.15e-16	255
GO:003133420	Oral cavity	OSCC	positive regulation of protein-containing complex assembly	153/7305	237/18723	1.18e-15	8.33e-14	153
GO:190290520	Oral cavity	OSCC	positive regulation of supramolecular fiber organization	131/7305	209/18723	3.18e-12	1.27e-10	131
GO:190290320	Oral cavity	OSCC	regulation of supramolecular fiber organization	211/7305	383/18723	9.45e-11	2.88e-09	211
GO:005149518	Oral cavity	OSCC	positive regulation of cytoskeleton organization	135/7305	226/18723	1.98e-10	5.66e-09	135
GO:005125820	Oral cavity	OSCC	protein polymerization	169/7305	297/18723	2.57e-10	7.17e-09	169
GO:003227319	Oral cavity	OSCC	positive regulation of protein polymerization	88/7305	138/18723	3.24e-09	7.39e-08	88
GO:003227120	Oral cavity	OSCC	regulation of protein polymerization	134/7305	233/18723	7.20e-09	1.51e-07	134
GO:00070204	Oral cavity	OSCC	microtubule nucleation	28/7305	35/18723	8.71e-07	1.19e-05	28
GO:00311226	Oral cavity	OSCC	cytoplasmic microtubule organization	39/7305	56/18723	3.29e-06	3.93e-05	39
GO:00467855	Oral cavity	OSCC	microtubule polymerization	53/7305	83/18723	3.96e-06	4.65e-05	53
GO:00705077	Oral cavity	OSCC	regulation of microtubule cytoskeleton organization	84/7305	148/18723	8.80e-06	9.33e-05	84
GO:00311127	Oral cavity	OSCC	positive regulation of microtubule polymerization or depolymerization	26/7305	37/18723	1.15e-04	8.35e-04	26
GO:00311093	Oral cavity	OSCC	microtubule polymerization or depolymerization	68/7305	122/18723	1.29e-04	9.21e-04	68
GO:00311137	Oral cavity	OSCC	regulation of microtubule polymerization	35/7305	55/18723	1.88e-04	1.27e-03	35
GO:00311167	Oral cavity	OSCC	positive regulation of microtubule polymerization	23/7305	33/18723	3.47e-04	2.12e-03	23
GO:00328863	Oral cavity	OSCC	regulation of microtubule-based process	115/7305	240/18723	2.95e-03	1.28e-02	115
GO:00311103	Oral cavity	OSCC	regulation of microtubule polymerization or depolymerization	47/7305	88/18723	4.23e-03	1.72e-02	47
GO:004325426	Oral cavity	EOLP	regulation of protein-containing complex assembly	112/2218	428/18723	1.58e-16	1.35e-13	112
GO:003133424	Oral cavity	EOLP	positive regulation of protein-containing complex assembly	67/2218	237/18723	4.77e-12	8.17e-10	67

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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

SLA

SNV

Missense_Mutation

rs772449159

c.142N>C

p.Thr48Pro

p.T48P

Q13239

protein_coding

tolerated(0.27)

benign(0.005)

TCGA-A2-A1G4-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

adriamycin

SLA

SNV

Missense_Mutation

rs772449159

c.142A>C

p.Thr48Pro

p.T48P

Q13239

protein_coding

tolerated(0.27)

benign(0.005)

TCGA-A8-A06R-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

SLA

SNV

Missense_Mutation

c.278N>G

p.Ser93Cys

p.S93C

Q13239

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SLA

SNV

Missense_Mutation

rs772449159

c.142A>C

p.Thr48Pro

p.T48P

Q13239

protein_coding

tolerated(0.27)

benign(0.005)

TCGA-BH-A1F5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SLA

SNV

Missense_Mutation

rs772449159

c.142N>C

p.Thr48Pro

p.T48P

Q13239

protein_coding

tolerated(0.27)

benign(0.005)

TCGA-C8-A273-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

SLA

SNV

Missense_Mutation

rs767082161

c.808N>G

p.Arg270Gly

p.R270G

Q13239

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SLA

SNV

Missense_Mutation

rs772449159

c.142A>C

p.Thr48Pro

p.T48P

Q13239

protein_coding

tolerated(0.27)

benign(0.005)

TCGA-E9-A1RE-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

SLA

SNV

Missense_Mutation

rs772449159

c.142A>C

p.Thr48Pro

p.T48P

Q13239

protein_coding

tolerated(0.27)

benign(0.005)

TCGA-E9-A22A-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

SLA

SNV

Missense_Mutation

rs376259266

c.157G>A

p.Glu53Lys

p.E53K

Q13239

protein_coding

tolerated(0.11)

possibly_damaging(0.572)

TCGA-JX-A3Q0-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

SLA

SNV

Missense_Mutation

novel

c.944N>T

p.Glu315Val

p.E315V

Q13239

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.998)

TCGA-VS-A94Z-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

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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