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: APLP2

Gene summary for APLP2

Gene summary.

Gene information	Species	Human
	Gene symbol	APLP2
	Gene ID	334
	Gene name	amyloid beta precursor like protein 2
	Gene Alias	APLP-2
	Cytomap	11q24.3
	Gene Type	protein-coding
	GO ID	GO:0006508
	UniProtAcc	A0A140VJE9

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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
334	APLP2	P10_cSCC	Human	Skin	cSCC	1.97e-35	1.58e+00	0.1017
334	APLP2	cSCC_p8	Human	Skin	cSCC	2.73e-05	-1.12e-01	-0.1971
334	APLP2	cSCC_p9	Human	Skin	cSCC	1.03e-03	-2.35e-01	-0.1991
334	APLP2	Pat01-B	Human	Stomach	GC	2.89e-37	4.69e-01	0.5754
334	APLP2	Pat02-B	Human	Stomach	GC	1.10e-54	3.39e-01	0.0368
334	APLP2	Pat03-B	Human	Stomach	GC	1.05e-43	3.94e-01	0.3693
334	APLP2	Pat04-B	Human	Stomach	GC	2.03e-25	1.67e-01	-0.1483
334	APLP2	Pat05-B	Human	Stomach	GC	1.64e-08	1.12e-01	-0.0353
334	APLP2	Pat06-B	Human	Stomach	GC	1.03e-54	2.02e-01	-0.1961
334	APLP2	Pat07-B	Human	Stomach	GC	1.10e-02	2.24e-02	0.0935
334	APLP2	Pat09-B	Human	Stomach	GC	5.24e-11	6.45e-02	-0.0359
334	APLP2	Pat11-B	Human	Stomach	GC	9.06e-19	2.35e-01	-0.182
334	APLP2	Pat12-B	Human	Stomach	GC	4.67e-30	2.73e-01	0.0325
334	APLP2	Pat13-B	Human	Stomach	GC	6.77e-11	1.58e-01	0.0555
334	APLP2	Pat15-B	Human	Stomach	GC	3.31e-18	2.01e-01	-0.0778
334	APLP2	Pat16-B	Human	Stomach	GC	2.72e-06	7.18e-02	0.1918
334	APLP2	Pat17-B	Human	Stomach	GC	1.23e-07	1.99e-01	0.3109
334	APLP2	Pat18-B	Human	Stomach	GC	1.32e-24	3.52e-01	-0.0432
334	APLP2	Pat19-B	Human	Stomach	GC	1.15e-19	2.90e-01	0.0826
334	APLP2	Pat22-B	Human	Stomach	GC	1.50e-48	2.48e-01	-0.1042

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
Prostate		BPH: Benign Prostatic Hyperplasia
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:0052547	Colorectum	AD	regulation of peptidase activity	137/3918	461/18723	4.12e-06	1.12e-04	137
GO:0045861	Colorectum	AD	negative regulation of proteolysis	106/3918	351/18723	2.33e-05	4.57e-04	106
GO:0052548	Colorectum	AD	regulation of endopeptidase activity	124/3918	432/18723	6.58e-05	1.07e-03	124
GO:00525471	Colorectum	SER	regulation of peptidase activity	114/2897	461/18723	1.18e-07	7.17e-06	114
GO:00458611	Colorectum	SER	negative regulation of proteolysis	88/2897	351/18723	1.74e-06	7.50e-05	88
GO:00525481	Colorectum	SER	regulation of endopeptidase activity	103/2897	432/18723	2.86e-06	1.16e-04	103
GO:0051346	Colorectum	SER	negative regulation of hydrolase activity	82/2897	379/18723	8.19e-04	1.01e-02	82
GO:0010466	Colorectum	SER	negative regulation of peptidase activity	57/2897	262/18723	4.15e-03	3.38e-02	57
GO:00525472	Colorectum	MSS	regulation of peptidase activity	130/3467	461/18723	1.81e-07	8.13e-06	130
GO:00525482	Colorectum	MSS	regulation of endopeptidase activity	117/3467	432/18723	6.25e-06	1.65e-04	117
GO:00458612	Colorectum	MSS	negative regulation of proteolysis	97/3467	351/18723	1.57e-05	3.54e-04	97
GO:00513461	Colorectum	MSS	negative regulation of hydrolase activity	92/3467	379/18723	2.85e-03	2.22e-02	92
GO:00458613	Colorectum	MSI-H	negative regulation of proteolysis	55/1319	351/18723	1.75e-08	1.98e-06	55
GO:00525473	Colorectum	MSI-H	regulation of peptidase activity	66/1319	461/18723	2.63e-08	2.81e-06	66
GO:00525483	Colorectum	MSI-H	regulation of endopeptidase activity	60/1319	432/18723	3.29e-07	2.57e-05	60
GO:00513462	Colorectum	MSI-H	negative regulation of hydrolase activity	48/1319	379/18723	5.58e-05	1.92e-03	48
GO:00104661	Colorectum	MSI-H	negative regulation of peptidase activity	35/1319	262/18723	1.95e-04	5.30e-03	35
GO:0010951	Colorectum	MSI-H	negative regulation of endopeptidase activity	33/1319	252/18723	4.22e-04	9.23e-03	33
GO:00525474	Colorectum	FAP	regulation of peptidase activity	86/2622	461/18723	2.98e-03	2.27e-02	86
GO:00458614	Colorectum	FAP	negative regulation of proteolysis	68/2622	351/18723	3.07e-03	2.31e-02	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

APLP2

SNV

Missense_Mutation

novel

c.1678N>A

p.Glu560Lys

p.E560K

Q06481

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

APLP2

SNV

Missense_Mutation

c.992N>G

p.Ser331Cys

p.S331C

Q06481

protein_coding

tolerated(0.08)

possibly_damaging(0.806)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

APLP2

insertion

In_Frame_Ins

novel

c.897_898insCTGGCT

p.Asp299_Lys300insLeuAla

p.D299_K300insLA

Q06481

protein_coding

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

APLP2

insertion

In_Frame_Ins

novel

c.899_900insCAT

p.Lys300delinsAsnMet

p.K300delinsNM

Q06481

protein_coding

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

APLP2

insertion

Frame_Shift_Ins

novel

c.887_888insTGCTAAACCATTTGAAAGTAAGTTGGGATATCACGACAGTT

p.Met297AlafsTer33

p.M297Afs*33

Q06481

protein_coding

TCGA-A8-A079-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

APLP2

insertion

Frame_Shift_Ins

novel

c.1651_1652insTTCGCTCAAGTGATCCTGCTGT

p.Pro551LeufsTer19

p.P551Lfs*19

Q06481

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

APLP2

insertion

In_Frame_Ins

novel

c.1084_1085insTTCTGCTAGAGTTGATTAAGCTTGCATTTCATT

p.Ala362delinsValLeuLeuGluLeuIleLysLeuAlaPheHisSer

p.A362delinsVLLELIKLAFHS

Q06481

protein_coding

TCGA-A8-A0A7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

APLP2

deletion

Frame_Shift_Del

c.1613delN

p.Arg539GlyfsTer15

p.R539Gfs*15

Q06481

protein_coding

TCGA-AR-A0TR-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

APLP2

insertion

Frame_Shift_Ins

novel

c.1866_1867insA

p.Gly625ArgfsTer20

p.G625Rfs*20

Q06481

protein_coding

TCGA-C8-A12X-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

APLP2

SNV

Missense_Mutation

rs141638912

c.974N>A

p.Arg325His

p.R325H

Q06481

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-2W-A8YY-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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