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: BCL2L12

Gene summary for BCL2L12

Gene summary.

Gene information	Species	Human
	Gene symbol	BCL2L12
	Gene ID	83596
	Gene name	BCL2 like 12
	Gene Alias	BCL2L12
	Cytomap	19q13.33
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	Q9HB09

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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
83596	BCL2L12	LZE4T	Human	Esophagus	ESCC	1.86e-09	2.73e-01	0.0811
83596	BCL2L12	LZE5T	Human	Esophagus	ESCC	7.46e-03	2.36e-01	0.0514
83596	BCL2L12	LZE7T	Human	Esophagus	ESCC	2.64e-12	4.91e-01	0.0667
83596	BCL2L12	LZE8T	Human	Esophagus	ESCC	3.11e-03	2.00e-01	0.067
83596	BCL2L12	LZE20T	Human	Esophagus	ESCC	2.22e-02	9.77e-02	0.0662
83596	BCL2L12	LZE22T	Human	Esophagus	ESCC	1.15e-07	6.08e-01	0.068
83596	BCL2L12	LZE24T	Human	Esophagus	ESCC	1.87e-15	4.73e-01	0.0596
83596	BCL2L12	LZE21T	Human	Esophagus	ESCC	1.39e-04	4.25e-01	0.0655
83596	BCL2L12	LZE6T	Human	Esophagus	ESCC	5.35e-03	1.75e-01	0.0845
83596	BCL2L12	P1T-E	Human	Esophagus	ESCC	1.04e-07	4.96e-01	0.0875
83596	BCL2L12	P2T-E	Human	Esophagus	ESCC	1.31e-21	5.11e-01	0.1177
83596	BCL2L12	P4T-E	Human	Esophagus	ESCC	2.14e-32	7.80e-01	0.1323
83596	BCL2L12	P5T-E	Human	Esophagus	ESCC	3.35e-18	3.99e-01	0.1327
83596	BCL2L12	P8T-E	Human	Esophagus	ESCC	2.37e-42	8.89e-01	0.0889
83596	BCL2L12	P9T-E	Human	Esophagus	ESCC	2.41e-12	3.12e-01	0.1131
83596	BCL2L12	P10T-E	Human	Esophagus	ESCC	2.23e-29	5.63e-01	0.116
83596	BCL2L12	P11T-E	Human	Esophagus	ESCC	1.77e-09	4.21e-01	0.1426
83596	BCL2L12	P12T-E	Human	Esophagus	ESCC	4.48e-30	6.32e-01	0.1122
83596	BCL2L12	P15T-E	Human	Esophagus	ESCC	6.03e-26	6.50e-01	0.1149
83596	BCL2L12	P16T-E	Human	Esophagus	ESCC	2.69e-15	2.36e-01	0.1153

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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
		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
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:009719112	Liver	Cirrhotic	extrinsic apoptotic signaling pathway	97/4634	219/18723	1.82e-10	9.11e-09	97
GO:00516046	Liver	Cirrhotic	protein maturation	121/4634	294/18723	3.54e-10	1.68e-08	121
GO:200123612	Liver	Cirrhotic	regulation of extrinsic apoptotic signaling pathway	72/4634	151/18723	7.80e-10	3.62e-08	72
GO:00432817	Liver	Cirrhotic	regulation of cysteine-type endopeptidase activity involved in apoptotic process	91/4634	209/18723	1.91e-09	7.98e-08	91
GO:004586112	Liver	Cirrhotic	negative regulation of proteolysis	136/4634	351/18723	3.46e-09	1.42e-07	136
GO:20001167	Liver	Cirrhotic	regulation of cysteine-type endopeptidase activity	97/4634	235/18723	1.61e-08	5.99e-07	97
GO:005134612	Liver	Cirrhotic	negative regulation of hydrolase activity	139/4634	379/18723	1.24e-07	3.42e-06	139
GO:00431546	Liver	Cirrhotic	negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	40/4634	78/18723	4.00e-07	9.39e-06	40
GO:001095111	Liver	Cirrhotic	negative regulation of endopeptidase activity	98/4634	252/18723	4.19e-07	9.77e-06	98
GO:001046612	Liver	Cirrhotic	negative regulation of peptidase activity	100/4634	262/18723	8.90e-07	1.84e-05	100
GO:20001177	Liver	Cirrhotic	negative regulation of cysteine-type endopeptidase activity	42/4634	86/18723	1.14e-06	2.31e-05	42
GO:00164853	Liver	Cirrhotic	protein processing	85/4634	225/18723	9.01e-06	1.32e-04	85
GO:1903317	Liver	Cirrhotic	regulation of protein maturation	28/4634	67/18723	1.60e-03	1.04e-02	28
GO:0070613	Liver	Cirrhotic	regulation of protein processing	26/4634	65/18723	4.73e-03	2.48e-02	26
GO:0010955	Liver	Cirrhotic	negative regulation of protein processing	14/4634	29/18723	5.09e-03	2.62e-02	14
GO:1903318	Liver	Cirrhotic	negative regulation of protein maturation	14/4634	29/18723	5.09e-03	2.62e-02	14
GO:200123322	Liver	HCC	regulation of apoptotic signaling pathway	226/7958	356/18723	7.26e-16	5.68e-14	226
GO:009719122	Liver	HCC	extrinsic apoptotic signaling pathway	143/7958	219/18723	6.99e-12	2.97e-10	143
GO:200123621	Liver	HCC	regulation of extrinsic apoptotic signaling pathway	98/7958	151/18723	2.17e-08	5.08e-07	98
GO:005160412	Liver	HCC	protein maturation	171/7958	294/18723	3.80e-08	8.30e-07	171

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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

BCL2L12

SNV

Missense_Mutation

c.848N>G

p.Ala283Gly

p.A283G

Q9HB09

protein_coding

deleterious(0.01)

probably_damaging(0.992)

TCGA-BH-A18V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

BCL2L12

SNV

Missense_Mutation

c.133N>G

p.Arg45Gly

p.R45G

Q9HB09

protein_coding

tolerated_low_confidence(0.11)

benign(0.03)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

BCL2L12

SNV

Missense_Mutation

novel

c.743N>A

p.Arg248His

p.R248H

Q9HB09

protein_coding

tolerated(0.06)

probably_damaging(0.996)

TCGA-AA-3556-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

BCL2L12

SNV

Missense_Mutation

novel

c.247G>A

p.Ala83Thr

p.A83T

Q9HB09

protein_coding

deleterious_low_confidence(0.01)

benign(0.01)

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

BCL2L12

insertion

Frame_Shift_Ins

novel

c.439_440insC

p.Ser149LeufsTer2

p.S149Lfs*2

Q9HB09

protein_coding

TCGA-AG-A02N-01

Colorectum

rectum adenocarcinoma

Male

>=65

I/II

Chemotherapy

folinic

BCL2L12

SNV

Missense_Mutation

novel

c.946N>A

p.Gly316Arg

p.G316R

Q9HB09

protein_coding

deleterious(0)

possibly_damaging(0.655)

TCGA-AJ-A8CV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

BCL2L12

SNV

Missense_Mutation

novel

c.163N>T

p.Val55Phe

p.V55F

Q9HB09

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.996)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

BCL2L12

SNV

Missense_Mutation

c.547N>C

p.Glu183Gln

p.E183Q

Q9HB09

protein_coding

deleterious(0.03)

probably_damaging(0.996)

TCGA-AP-A0LI-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Chemotherapy

paclitaxel

BCL2L12

SNV

Missense_Mutation

novel

c.446N>G

p.Ser149Cys

p.S149C

Q9HB09

protein_coding

deleterious_low_confidence(0)

benign(0.01)

TCGA-AX-A2IO-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

BCL2L12

SNV

Missense_Mutation

rs747252998

c.895N>A

p.Gly299Arg

p.G299R

Q9HB09

protein_coding

deleterious(0)

possibly_damaging(0.758)

TCGA-B5-A0JV-01

Endometrium

uterine corpus endometrioid 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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