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:2001233111	Esophagus	ESCC	regulation of apoptotic signaling pathway	256/8552	356/18723	4.11e-24	1.04e-21	256
GO:0097191111	Esophagus	ESCC	extrinsic apoptotic signaling pathway	159/8552	219/18723	4.12e-16	2.94e-14	159
GO:2001236111	Esophagus	ESCC	regulation of extrinsic apoptotic signaling pathway	111/8552	151/18723	2.97e-12	1.18e-10	111
GO:2000116111	Esophagus	ESCC	regulation of cysteine-type endopeptidase activity	158/8552	235/18723	1.67e-11	5.90e-10	158
GO:0043281111	Esophagus	ESCC	regulation of cysteine-type endopeptidase activity involved in apoptotic process	143/8552	209/18723	2.12e-11	7.31e-10	143
GO:005160418	Esophagus	ESCC	protein maturation	189/8552	294/18723	7.64e-11	2.39e-09	189
GO:0052547111	Esophagus	ESCC	regulation of peptidase activity	275/8552	461/18723	7.54e-10	1.88e-08	275
GO:0052548111	Esophagus	ESCC	regulation of endopeptidase activity	253/8552	432/18723	3.68e-08	6.78e-07	253
GO:2000117110	Esophagus	ESCC	negative regulation of cysteine-type endopeptidase activity	63/8552	86/18723	1.84e-07	2.88e-06	63
GO:0043154110	Esophagus	ESCC	negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	58/8552	78/18723	2.38e-07	3.61e-06	58
GO:001648514	Esophagus	ESCC	protein processing	134/8552	225/18723	1.81e-05	1.60e-04	134
GO:0045861111	Esophagus	ESCC	negative regulation of proteolysis	195/8552	351/18723	1.13e-04	7.85e-04	195
GO:0051346110	Esophagus	ESCC	negative regulation of hydrolase activity	208/8552	379/18723	1.76e-04	1.14e-03	208
GO:001046620	Esophagus	ESCC	negative regulation of peptidase activity	140/8552	262/18723	6.73e-03	2.46e-02	140
GO:001095119	Esophagus	ESCC	negative regulation of endopeptidase activity	135/8552	252/18723	6.86e-03	2.51e-02	135
GO:001095511	Esophagus	ESCC	negative regulation of protein processing	20/8552	29/18723	9.66e-03	3.34e-02	20
GO:190331811	Esophagus	ESCC	negative regulation of protein maturation	20/8552	29/18723	9.66e-03	3.34e-02	20
GO:200123312	Liver	Cirrhotic	regulation of apoptotic signaling pathway	163/4634	356/18723	2.62e-18	4.43e-16	163
GO:005254712	Liver	Cirrhotic	regulation of peptidase activity	185/4634	461/18723	1.32e-13	1.09e-11	185
GO:005254812	Liver	Cirrhotic	regulation of endopeptidase activity	172/4634	432/18723	2.12e-12	1.58e-10	172

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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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