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: SORL1

Gene summary for SORL1

Gene summary.

Gene information	Species	Human
	Gene symbol	SORL1
	Gene ID	6653
	Gene name	sortilin related receptor 1
	Gene Alias	C11orf32
	Cytomap	11q24.1
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	A0A024R3H2

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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
6653	SORL1	CA_HPV_2	Human	Cervix	CC	4.09e-02	-3.72e-01	0.0391
6653	SORL1	CA_HPV_3	Human	Cervix	CC	1.42e-09	-3.26e-01	0.0414
6653	SORL1	N_HPV_1	Human	Cervix	N_HPV	6.72e-06	-4.26e-01	0.0079
6653	SORL1	N_HPV_2	Human	Cervix	N_HPV	1.84e-02	-1.68e-01	-0.0131
6653	SORL1	CCI_1	Human	Cervix	CC	1.15e-03	-5.73e-01	0.528
6653	SORL1	CCII_1	Human	Cervix	CC	4.24e-11	-6.02e-01	0.3249
6653	SORL1	Tumor	Human	Cervix	CC	1.54e-07	-4.53e-01	0.1241
6653	SORL1	sample1	Human	Cervix	CC	2.76e-11	-6.14e-01	0.0959
6653	SORL1	sample3	Human	Cervix	CC	6.79e-09	-4.11e-01	0.1387
6653	SORL1	L1	Human	Cervix	CC	7.48e-07	-5.13e-01	0.0802
6653	SORL1	T1	Human	Cervix	CC	5.26e-19	-5.89e-01	0.0918
6653	SORL1	T3	Human	Cervix	CC	1.17e-06	-3.97e-01	0.1389
6653	SORL1	HTA11_1938_2000001011	Human	Colorectum	AD	1.38e-11	8.42e-01	-0.0811
6653	SORL1	HTA11_78_2000001011	Human	Colorectum	AD	1.85e-02	4.46e-01	-0.1088
6653	SORL1	HTA11_347_2000001011	Human	Colorectum	AD	1.62e-23	9.15e-01	-0.1954
6653	SORL1	HTA11_411_2000001011	Human	Colorectum	SER	1.41e-03	9.47e-01	-0.2602
6653	SORL1	HTA11_5212_2000001011	Human	Colorectum	AD	1.43e-03	6.84e-01	-0.2061
6653	SORL1	HTA11_6818_2000001021	Human	Colorectum	AD	4.15e-07	6.49e-01	0.0588
6653	SORL1	HTA11_99999965104_69814	Human	Colorectum	MSS	2.42e-04	5.47e-01	0.281
6653	SORL1	HTA11_99999971662_82457	Human	Colorectum	MSS	7.31e-07	6.56e-01	0.3859

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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
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:004217610	Cervix	CC	regulation of protein catabolic process	104/2311	391/18723	9.39e-15	9.36e-12	104
GO:005254710	Cervix	CC	regulation of peptidase activity	112/2311	461/18723	6.70e-13	3.08e-10	112
GO:005254810	Cervix	CC	regulation of endopeptidase activity	103/2311	432/18723	1.89e-11	5.14e-09	103
GO:004573210	Cervix	CC	positive regulation of protein catabolic process	65/2311	231/18723	7.44e-11	1.39e-08	65
GO:00725949	Cervix	CC	establishment of protein localization to organelle	99/2311	422/18723	1.23e-10	2.11e-08	99
GO:190382910	Cervix	CC	positive regulation of cellular protein localization	72/2311	276/18723	3.20e-10	4.46e-08	72
GO:000989610	Cervix	CC	positive regulation of catabolic process	109/2311	492/18723	5.26e-10	6.99e-08	109
GO:004325410	Cervix	CC	regulation of protein-containing complex assembly	96/2311	428/18723	2.91e-09	3.05e-07	96
GO:00512359	Cervix	CC	maintenance of location	78/2311	327/18723	5.18e-09	4.92e-07	78
GO:005122210	Cervix	CC	positive regulation of protein transport	72/2311	303/18723	2.36e-08	1.70e-06	72
GO:004586110	Cervix	CC	negative regulation of proteolysis	80/2311	351/18723	2.88e-08	1.98e-06	80
GO:005165110	Cervix	CC	maintenance of location in cell	55/2311	214/18723	6.63e-08	3.85e-06	55
GO:190495110	Cervix	CC	positive regulation of establishment of protein localization	73/2311	319/18723	9.69e-08	5.25e-06	73
GO:003133010	Cervix	CC	negative regulation of cellular catabolic process	63/2311	262/18723	1.10e-07	5.68e-06	63
GO:005109810	Cervix	CC	regulation of binding	80/2311	363/18723	1.32e-07	6.42e-06	80
GO:00513469	Cervix	CC	negative regulation of hydrolase activity	81/2311	379/18723	4.27e-07	1.67e-05	81
GO:00018197	Cervix	CC	positive regulation of cytokine production	95/2311	467/18723	4.88e-07	1.85e-05	95
GO:00104669	Cervix	CC	negative regulation of peptidase activity	60/2311	262/18723	1.27e-06	4.34e-05	60
GO:000989510	Cervix	CC	negative regulation of catabolic process	69/2311	320/18723	2.15e-06	6.55e-05	69
GO:000660510	Cervix	CC	protein targeting	68/2311	314/18723	2.17e-06	6.55e-05	68

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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

SORL1

SNV

Missense_Mutation

novel

c.1999N>A

p.Asp667Asn

p.D667N

Q92673

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SORL1

SNV

Missense_Mutation

c.883N>A

p.Glu295Lys

p.E295K

Q92673

protein_coding

deleterious(0.02)

probably_damaging(0.989)

TCGA-AO-A0JC-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

SORL1

SNV

Missense_Mutation

novel

c.3388A>T

p.Thr1130Ser

p.T1130S

Q92673

protein_coding

tolerated(0.71)

benign(0.007)

TCGA-BH-A0E2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

SORL1

SNV

Missense_Mutation

novel

c.529N>C

p.Tyr177His

p.Y177H

Q92673

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SORL1

SNV

Missense_Mutation

c.1426C>T

p.His476Tyr

p.H476Y

Q92673

protein_coding

deleterious(0)

possibly_damaging(0.852)

TCGA-D8-A1XM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SORL1

SNV

Missense_Mutation

rs149445303

c.5627N>T

p.Thr1876Met

p.T1876M

Q92673

protein_coding

deleterious(0.01)

probably_damaging(0.997)

TCGA-E9-A243-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

SORL1

insertion

Frame_Shift_Ins

novel

c.4917_4918insATTGTTGGGATTCATCTCATTGTTATTTCTGTTACTCAAACCA

p.Asp1640IlefsTer60

p.D1640Ifs*60

Q92673

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

SORL1

insertion

Frame_Shift_Ins

novel

c.2838_2839insTATTA

p.Thr947TyrfsTer2

p.T947Yfs*2

Q92673

protein_coding

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

SORL1

insertion

In_Frame_Ins

novel

c.4008_4009insCTGTATCAGATGGCACTCCCAGCGTGCCGTAGCCCCTTACCC

p.Val1336_Cys1337insLeuTyrGlnMetAlaLeuProAlaCysArgSerProLeuPro

p.V1336_C1337insLYQMALPACRSPLP

Q92673

protein_coding

TCGA-A8-A097-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

SORL1

insertion

Frame_Shift_Ins

novel

c.5847_5848insTTTTGCAAATGTTCCGGTGCCCCTGCTGCTCTTGGAT

p.Ile1950PhefsTer20

p.I1950Ffs*20

Q92673

protein_coding

TCGA-B6-A0IM-01

Breast

breast invasive 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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