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: MTOR

Gene summary for MTOR

Gene summary.

Gene information	Species	Human
	Gene symbol	MTOR
	Gene ID	2475
	Gene name	mechanistic target of rapamycin kinase
	Gene Alias	FRAP
	Cytomap	1p36.22
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P42345

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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
2475	MTOR	LZE4T	Human	Esophagus	ESCC	5.59e-03	1.11e-01	0.0811
2475	MTOR	LZE7T	Human	Esophagus	ESCC	1.14e-07	3.37e-01	0.0667
2475	MTOR	LZE22T	Human	Esophagus	ESCC	5.81e-05	2.77e-01	0.068
2475	MTOR	LZE24T	Human	Esophagus	ESCC	2.01e-06	1.95e-01	0.0596
2475	MTOR	P1T-E	Human	Esophagus	ESCC	9.72e-03	1.92e-01	0.0875
2475	MTOR	P2T-E	Human	Esophagus	ESCC	8.23e-15	2.40e-01	0.1177
2475	MTOR	P4T-E	Human	Esophagus	ESCC	1.45e-03	1.53e-01	0.1323
2475	MTOR	P5T-E	Human	Esophagus	ESCC	1.05e-05	1.06e-01	0.1327
2475	MTOR	P8T-E	Human	Esophagus	ESCC	5.70e-08	1.83e-01	0.0889
2475	MTOR	P9T-E	Human	Esophagus	ESCC	1.17e-07	1.58e-01	0.1131
2475	MTOR	P10T-E	Human	Esophagus	ESCC	1.02e-11	3.18e-01	0.116
2475	MTOR	P11T-E	Human	Esophagus	ESCC	1.64e-03	2.21e-01	0.1426
2475	MTOR	P12T-E	Human	Esophagus	ESCC	2.79e-05	1.63e-01	0.1122
2475	MTOR	P15T-E	Human	Esophagus	ESCC	1.78e-16	3.60e-01	0.1149
2475	MTOR	P16T-E	Human	Esophagus	ESCC	5.11e-04	1.50e-01	0.1153
2475	MTOR	P17T-E	Human	Esophagus	ESCC	3.33e-07	3.42e-01	0.1278
2475	MTOR	P19T-E	Human	Esophagus	ESCC	4.16e-05	3.45e-01	0.1662
2475	MTOR	P20T-E	Human	Esophagus	ESCC	4.86e-10	2.31e-01	0.1124
2475	MTOR	P21T-E	Human	Esophagus	ESCC	1.81e-22	4.41e-01	0.1617
2475	MTOR	P22T-E	Human	Esophagus	ESCC	2.19e-12	1.39e-01	0.1236

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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
Liver		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
Prostate		BPH: Benign Prostatic Hyperplasia

∗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:00016678	Breast	Precancer	ameboidal-type cell migration	47/1080	475/18723	2.19e-04	3.35e-03	47
GO:00160497	Breast	Precancer	cell growth	46/1080	482/18723	5.63e-04	7.16e-03	46
GO:00192164	Breast	Precancer	regulation of lipid metabolic process	34/1080	331/18723	8.14e-04	9.55e-03	34
GO:00015587	Breast	Precancer	regulation of cell growth	39/1080	414/18723	1.81e-03	1.78e-02	39
GO:00011015	Breast	Precancer	response to acid chemical	16/1080	135/18723	4.85e-03	3.67e-02	16
GO:01501158	Breast	Precancer	cell-substrate junction organization	13/1080	101/18723	5.30e-03	3.94e-02	13
GO:01501168	Breast	Precancer	regulation of cell-substrate junction organization	10/1080	71/18723	7.33e-03	4.88e-02	10
GO:000166714	Breast	IDC	ameboidal-type cell migration	64/1434	475/18723	6.65e-06	2.05e-04	64
GO:001921612	Breast	IDC	regulation of lipid metabolic process	45/1434	331/18723	1.21e-04	2.24e-03	45
GO:00192184	Breast	IDC	regulation of steroid metabolic process	18/1434	100/18723	5.40e-04	6.96e-03	18
GO:001604913	Breast	IDC	cell growth	56/1434	482/18723	1.16e-03	1.26e-02	56
GO:000155813	Breast	IDC	regulation of cell growth	49/1434	414/18723	1.55e-03	1.55e-02	49
GO:000110112	Breast	IDC	response to acid chemical	20/1434	135/18723	3.28e-03	2.75e-02	20
GO:00431126	Breast	IDC	receptor metabolic process	23/1434	166/18723	4.04e-03	3.25e-02	23
GO:00432003	Breast	IDC	response to amino acid	17/1434	116/18723	7.13e-03	4.92e-02	17
GO:000166723	Breast	DCIS	ameboidal-type cell migration	62/1390	475/18723	9.60e-06	2.56e-04	62
GO:001921621	Breast	DCIS	regulation of lipid metabolic process	43/1390	331/18723	2.37e-04	3.71e-03	43
GO:001604923	Breast	DCIS	cell growth	54/1390	482/18723	1.60e-03	1.59e-02	54
GO:000155822	Breast	DCIS	regulation of cell growth	47/1390	414/18723	2.39e-03	2.16e-02	47
GO:004311213	Breast	DCIS	receptor metabolic process	23/1390	166/18723	2.75e-03	2.41e-02	23

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0521231	Liver	HCC	Pancreatic cancer	54/4020	76/8465	2.50e-05	1.64e-04	9.12e-05	54
hsa0522511	Liver	HCC	Hepatocellular carcinoma	106/4020	168/8465	2.87e-05	1.85e-04	1.03e-04	106
hsa0501731	Liver	HCC	Spinocerebellar ataxia	92/4020	143/8465	3.20e-05	1.88e-04	1.04e-04	92
hsa0421131	Liver	HCC	Longevity regulating pathway	61/4020	89/8465	4.46e-05	2.37e-04	1.32e-04	61
hsa0415251	Liver	HCC	AMPK signaling pathway	77/4020	121/8465	2.32e-04	1.11e-03	6.18e-04	77
hsa0406632	Liver	HCC	HIF-1 signaling pathway	70/4020	109/8465	2.96e-04	1.36e-03	7.57e-04	70
hsa051653	Liver	HCC	Human papillomavirus infection	188/4020	331/8465	3.34e-04	1.49e-03	8.29e-04	188
hsa0517012	Liver	HCC	Human immunodeficiency virus 1 infection	125/4020	212/8465	4.51e-04	1.94e-03	1.08e-03	125
hsa0415011	Liver	HCC	mTOR signaling pathway	95/4020	156/8465	4.70e-04	1.99e-03	1.11e-03	95
hsa0520531	Liver	HCC	Proteoglycans in cancer	121/4020	205/8465	5.22e-04	2.18e-03	1.21e-03	121
hsa0516332	Liver	HCC	Human cytomegalovirus infection	131/4020	225/8465	6.86e-04	2.77e-03	1.54e-03	131
hsa0491913	Liver	HCC	Thyroid hormone signaling pathway	75/4020	121/8465	8.76e-04	3.38e-03	1.88e-03	75
hsa0401211	Liver	HCC	ErbB signaling pathway	54/4020	85/8465	2.02e-03	7.07e-03	3.93e-03	54
hsa049203	Liver	HCC	Adipocytokine signaling pathway	45/4020	69/8465	2.19e-03	7.55e-03	4.20e-03	45
hsa0421311	Liver	HCC	Longevity regulating pathway - multiple species	41/4020	62/8465	2.30e-03	7.86e-03	4.37e-03	41
hsa0516731	Liver	HCC	Kaposi sarcoma-associated herpesvirus infection	111/4020	194/8465	3.78e-03	1.16e-02	6.45e-03	111
hsa0521411	Liver	HCC	Glioma	47/4020	75/8465	5.67e-03	1.62e-02	9.02e-03	47
hsa0152131	Liver	HCC	EGFR tyrosine kinase inhibitor resistance	48/4020	79/8465	1.19e-02	2.99e-02	1.66e-02	48
hsa015221	Liver	HCC	Endocrine resistance	58/4020	98/8465	1.28e-02	3.19e-02	1.78e-02	58
hsa0523031	Liver	HCC	Central carbon metabolism in cancer	43/4020	70/8465	1.30e-02	3.19e-02	1.78e-02	43

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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

MTOR

SNV

Missense_Mutation

novel

c.7184A>G

p.Asn2395Ser

p.N2395S

P42345

protein_coding

tolerated(1)

possibly_damaging(0.703)

TCGA-A2-A0D2-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

MTOR

SNV

Missense_Mutation

c.7498N>T

p.Ile2500Phe

p.I2500F

P42345

protein_coding

deleterious(0)

probably_damaging(0.926)

TCGA-A8-A06Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

MTOR

SNV

Missense_Mutation

rs769877976

c.25G>A

p.Ala9Thr

p.A9T

P42345

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.835)

TCGA-A8-A08S-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

MTOR

SNV

Missense_Mutation

novel

c.6287N>T

p.Asp2096Val

p.D2096V

P42345

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AN-A03Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MTOR

SNV

Missense_Mutation

novel

c.3142A>C

p.Ile1048Leu

p.I1048L

P42345

protein_coding

tolerated(1)

benign(0)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MTOR

SNV

Missense_Mutation

novel

c.5276N>G

p.Leu1759Arg

p.L1759R

P42345

protein_coding

tolerated(0.51)

probably_damaging(0.995)

TCGA-BH-A0AZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

MTOR

SNV

Missense_Mutation

c.397N>G

p.Leu133Val

p.L133V

P42345

protein_coding

deleterious(0)

possibly_damaging(0.563)

TCGA-BH-A0DZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

MTOR

SNV

Missense_Mutation

c.4835N>C

p.Arg1612Pro

p.R1612P

P42345

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

MTOR

SNV

Missense_Mutation

novel

c.3722N>G

p.Gln1241Arg

p.Q1241R

P42345

protein_coding

tolerated(0.44)

benign(0.003)

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MTOR

SNV

Missense_Mutation

c.7162N>C

p.Glu2388Gln

p.E2388Q

P42345

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

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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
2475	MTOR	DRUG RESISTANCE, CLINICALLY ACTIONABLE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE, ENZYME		QUINACRINE	QUINACRINE
2475	MTOR	DRUG RESISTANCE, CLINICALLY ACTIONABLE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE, ENZYME	inhibitor	BEZ235	DACTOLISIB
2475	MTOR	DRUG RESISTANCE, CLINICALLY ACTIONABLE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE, ENZYME		TCMDC-125575	CHEMBL587620
2475	MTOR	DRUG RESISTANCE, CLINICALLY ACTIONABLE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE, ENZYME		PERPHENAZINE	PERPHENAZINE
2475	MTOR	DRUG RESISTANCE, CLINICALLY ACTIONABLE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE, ENZYME		PAZOPANIB	PAZOPANIB	24625776
2475	MTOR	DRUG RESISTANCE, CLINICALLY ACTIONABLE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE, ENZYME	inhibitor	249565693
2475	MTOR	DRUG RESISTANCE, CLINICALLY ACTIONABLE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE, ENZYME		CAFFEIC ACID PHENETHYL ESTER	CAFFEIC ACID PHENETHYL ESTER
2475	MTOR	DRUG RESISTANCE, CLINICALLY ACTIONABLE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE, ENZYME		AZD2014	VISTUSERTIB
2475	MTOR	DRUG RESISTANCE, CLINICALLY ACTIONABLE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE, ENZYME		GDC-0980/RG7422
2475	MTOR	DRUG RESISTANCE, CLINICALLY ACTIONABLE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE, ENZYME		EVEROLIMUS	EVEROLIMUS	24625776,25295501

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