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: AMOTL2

Gene summary for AMOTL2

Gene summary.

Gene information	Species	Human
	Gene symbol	AMOTL2
	Gene ID	51421
	Gene name	angiomotin like 2
	Gene Alias	LCCP
	Cytomap	3q22.2
	Gene Type	protein-coding
	GO ID	GO:0001525
	UniProtAcc	Q9Y2J4

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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
51421	AMOTL2	ATC3	Human	Thyroid	ATC	4.20e-05	1.77e-01	0.338
51421	AMOTL2	ATC5	Human	Thyroid	ATC	1.38e-13	-1.53e-02	0.34

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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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:001605517	Esophagus	ESCC	Wnt signaling pathway	268/8552	444/18723	2.32e-10	6.58e-09	268
GO:019873817	Esophagus	ESCC	cell-cell signaling by wnt	269/8552	446/18723	2.41e-10	6.79e-09	269
GO:000716320	Esophagus	ESCC	establishment or maintenance of cell polarity	143/8552	218/18723	2.05e-09	4.65e-08	143
GO:003001018	Esophagus	ESCC	establishment of cell polarity	96/8552	143/18723	1.69e-07	2.67e-06	96
GO:000166720	Esophagus	ESCC	ameboidal-type cell migration	250/8552	475/18723	1.22e-03	5.97e-03	250
GO:00353297	Esophagus	ESCC	hippo signaling	26/8552	40/18723	1.08e-02	3.66e-02	26
GO:000716318	Oral cavity	OSCC	establishment or maintenance of cell polarity	129/7305	218/18723	1.16e-09	2.86e-08	129
GO:001605510	Oral cavity	OSCC	Wnt signaling pathway	227/7305	444/18723	1.10e-07	1.87e-06	227
GO:019873810	Oral cavity	OSCC	cell-cell signaling by wnt	227/7305	446/18723	1.75e-07	2.86e-06	227
GO:003001016	Oral cavity	OSCC	establishment of cell polarity	82/7305	143/18723	6.56e-06	7.24e-05	82
GO:000166719	Oral cavity	OSCC	ameboidal-type cell migration	228/7305	475/18723	3.46e-05	3.10e-04	228
GO:000716319	Oral cavity	LP	establishment or maintenance of cell polarity	79/4623	218/18723	8.84e-05	1.11e-03	79
GO:001605515	Oral cavity	LP	Wnt signaling pathway	140/4623	444/18723	5.80e-04	5.35e-03	140
GO:019873815	Oral cavity	LP	cell-cell signaling by wnt	140/4623	446/18723	7.12e-04	6.38e-03	140
GO:003001017	Oral cavity	LP	establishment of cell polarity	49/4623	143/18723	6.33e-03	3.73e-02	49
GO:000166728	Thyroid	HT	ameboidal-type cell migration	52/1272	475/18723	4.54e-04	5.53e-03	52
GO:000716328	Thyroid	HT	establishment or maintenance of cell polarity	28/1272	218/18723	8.66e-04	9.20e-03	28
GO:001605520	Thyroid	HT	Wnt signaling pathway	48/1272	444/18723	9.68e-04	9.93e-03	48
GO:019873820	Thyroid	HT	cell-cell signaling by wnt	48/1272	446/18723	1.07e-03	1.07e-02	48
GO:00353298	Thyroid	HT	hippo signaling	8/1272	40/18723	4.84e-03	3.32e-02	8

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04530211	Esophagus	ESCC	Tight junction	105/4205	169/8465	6.73e-04	2.23e-03	1.14e-03	105
hsa04530310	Esophagus	ESCC	Tight junction	105/4205	169/8465	6.73e-04	2.23e-03	1.14e-03	105
hsa0453030	Oral cavity	OSCC	Tight junction	102/3704	169/8465	8.68e-06	3.93e-05	2.00e-05	102
hsa04530114	Oral cavity	OSCC	Tight junction	102/3704	169/8465	8.68e-06	3.93e-05	2.00e-05	102

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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

AMOTL2

SNV

Missense_Mutation

novel

c.1282N>A

p.Glu428Lys

p.E428K

Q9Y2J4

protein_coding

deleterious(0)

probably_damaging(0.913)

TCGA-AN-A0FV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

AMOTL2

SNV

Missense_Mutation

c.355G>A

p.Glu119Lys

p.E119K

Q9Y2J4

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

AMOTL2

insertion

Nonsense_Mutation

novel

c.1562_1563insATTACAGGCATGAGC

p.Gly521_Asn522insLeuGlnAlaTerAla

p.G521_N522insLQA*A

Q9Y2J4

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

AMOTL2

SNV

Missense_Mutation

novel

c.803N>A

p.Pro268Gln

p.P268Q

Q9Y2J4

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-C5-A901-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

AMOTL2

SNV

Missense_Mutation

c.2410G>C

p.Asp804His

p.D804H

Q9Y2J4

protein_coding

deleterious(0.03)

possibly_damaging(0.501)

TCGA-DG-A2KM-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

AMOTL2

SNV

Missense_Mutation

novel

c.551N>A

p.Pro184Gln

p.P184Q

Q9Y2J4

protein_coding

tolerated(0.23)

benign(0.282)

TCGA-DS-A1OD-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

AMOTL2

SNV

Missense_Mutation

novel

c.1940C>T

p.Thr647Met

p.T647M

Q9Y2J4

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-EA-A3HS-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

AMOTL2

SNV

Missense_Mutation

novel

c.1132N>C

p.Glu378Gln

p.E378Q

Q9Y2J4

protein_coding

tolerated(0.12)

possibly_damaging(0.477)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

AMOTL2

SNV

Missense_Mutation

novel

c.1159N>A

p.Glu387Lys

p.E387K

Q9Y2J4

protein_coding

deleterious(0.02)

possibly_damaging(0.541)

TCGA-IR-A3LH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

AMOTL2

SNV

Missense_Mutation

novel

c.1243N>A

p.Glu415Lys

p.E415K

Q9Y2J4

protein_coding

deleterious(0.02)

probably_damaging(0.913)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

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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