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: PPP1R12B

Gene summary for PPP1R12B

Gene summary.

Gene information	Species	Human
	Gene symbol	PPP1R12B
	Gene ID	4660
	Gene name	protein phosphatase 1 regulatory subunit 12B
	Gene Alias	MYPT2
	Cytomap	1q32.1
	Gene Type	protein-coding
	GO ID	GO:0003008
	UniProtAcc	O60237

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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
4660	PPP1R12B	CCI_1	Human	Cervix	CC	1.46e-11	1.21e+00	0.528
4660	PPP1R12B	CCI_3	Human	Cervix	CC	1.12e-28	1.74e+00	0.516
4660	PPP1R12B	HTA11_3410_2000001011	Human	Colorectum	AD	5.00e-26	-6.78e-01	0.0155
4660	PPP1R12B	HTA11_2951_2000001011	Human	Colorectum	AD	5.82e-05	-9.59e-01	0.0216
4660	PPP1R12B	HTA11_347_2000001011	Human	Colorectum	AD	1.44e-11	6.31e-01	-0.1954
4660	PPP1R12B	HTA11_3361_2000001011	Human	Colorectum	AD	2.16e-12	-6.47e-01	-0.1207
4660	PPP1R12B	HTA11_9341_2000001011	Human	Colorectum	SER	1.72e-03	-9.06e-01	-0.00410000000000005
4660	PPP1R12B	HTA11_866_3004761011	Human	Colorectum	AD	2.63e-03	-4.73e-01	0.096
4660	PPP1R12B	HTA11_8622_2000001021	Human	Colorectum	SER	1.76e-05	-5.45e-01	0.0528
4660	PPP1R12B	HTA11_10711_2000001011	Human	Colorectum	AD	1.38e-16	-7.26e-01	0.0338
4660	PPP1R12B	HTA11_7696_3000711011	Human	Colorectum	AD	2.77e-08	-4.96e-01	0.0674
4660	PPP1R12B	HTA11_7469_2000001011	Human	Colorectum	AD	6.50e-03	-4.84e-01	-0.0124
4660	PPP1R12B	HTA11_6818_2000001021	Human	Colorectum	AD	4.46e-05	-5.18e-01	0.0588
4660	PPP1R12B	HTA11_99999970781_79442	Human	Colorectum	MSS	6.76e-10	-4.45e-01	0.294
4660	PPP1R12B	HTA11_99999971662_82457	Human	Colorectum	MSS	3.08e-13	-5.52e-01	0.3859
4660	PPP1R12B	HTA11_99999973899_84307	Human	Colorectum	MSS	8.72e-13	-8.95e-01	0.2585
4660	PPP1R12B	HTA11_99999974143_84620	Human	Colorectum	MSS	4.06e-47	-9.40e-01	0.3005
4660	PPP1R12B	A001-C-207	Human	Colorectum	FAP	9.75e-05	-4.19e-01	0.1278
4660	PPP1R12B	A015-C-203	Human	Colorectum	FAP	9.00e-45	-8.30e-01	-0.1294
4660	PPP1R12B	A015-C-204	Human	Colorectum	FAP	5.77e-11	-6.09e-01	-0.0228

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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
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

∗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:00902578	Cervix	CC	regulation of muscle system process	45/2311	252/18723	6.73e-03	3.70e-02	45
GO:0090257	Colorectum	AD	regulation of muscle system process	73/3918	252/18723	1.46e-03	1.24e-02	73
GO:00902571	Colorectum	SER	regulation of muscle system process	60/2897	252/18723	3.28e-04	5.22e-03	60
GO:0003012	Colorectum	SER	muscle system process	92/2897	452/18723	2.98e-03	2.63e-02	92
GO:00902572	Colorectum	MSS	regulation of muscle system process	66/3467	252/18723	1.55e-03	1.41e-02	66
GO:00030121	Colorectum	MSS	muscle system process	105/3467	452/18723	6.39e-03	4.26e-02	105
GO:00902574	Colorectum	FAP	regulation of muscle system process	58/2622	252/18723	7.22e-05	1.33e-03	58
GO:00030122	Colorectum	FAP	muscle system process	89/2622	452/18723	4.63e-04	5.39e-03	89
GO:00069371	Colorectum	FAP	regulation of muscle contraction	37/2622	169/18723	3.39e-03	2.47e-02	37
GO:00902575	Colorectum	CRC	regulation of muscle system process	51/2078	252/18723	1.49e-05	4.63e-04	51
GO:00030123	Colorectum	CRC	muscle system process	74/2078	452/18723	3.92e-04	5.80e-03	74
GO:00069372	Colorectum	CRC	regulation of muscle contraction	33/2078	169/18723	8.65e-04	1.07e-02	33
GO:00030124	Lung	IAC	muscle system process	71/2061	452/18723	1.29e-03	1.45e-02	71
GO:00902577	Lung	IAC	regulation of muscle system process	43/2061	252/18723	2.35e-03	2.28e-02	43
GO:000301211	Lung	AIS	muscle system process	63/1849	452/18723	3.18e-03	3.05e-02	63
GO:00030128	Oral cavity	EOLP	muscle system process	71/2218	452/18723	7.83e-03	3.73e-02	71

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0520516	Cervix	CC	Proteoglycans in cancer	60/1267	205/8465	9.13e-08	1.18e-06	7.00e-07	60
hsa0451010	Cervix	CC	Focal adhesion	59/1267	203/8465	1.53e-07	1.84e-06	1.09e-06	59
hsa0481016	Cervix	CC	Regulation of actin cytoskeleton	64/1267	229/8465	2.24e-07	2.59e-06	1.53e-06	64
hsa049218	Cervix	CC	Oxytocin signaling pathway	34/1267	154/8465	1.12e-02	3.42e-02	2.02e-02	34
hsa0520517	Cervix	CC	Proteoglycans in cancer	60/1267	205/8465	9.13e-08	1.18e-06	7.00e-07	60
hsa0451014	Cervix	CC	Focal adhesion	59/1267	203/8465	1.53e-07	1.84e-06	1.09e-06	59
hsa0481017	Cervix	CC	Regulation of actin cytoskeleton	64/1267	229/8465	2.24e-07	2.59e-06	1.53e-06	64
hsa0492111	Cervix	CC	Oxytocin signaling pathway	34/1267	154/8465	1.12e-02	3.42e-02	2.02e-02	34
hsa05205	Colorectum	AD	Proteoglycans in cancer	70/2092	205/8465	1.37e-03	8.46e-03	5.39e-03	70
hsa04810	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa04510	Colorectum	AD	Focal adhesion	67/2092	203/8465	4.40e-03	2.17e-02	1.38e-02	67
hsa052051	Colorectum	AD	Proteoglycans in cancer	70/2092	205/8465	1.37e-03	8.46e-03	5.39e-03	70
hsa048101	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa045101	Colorectum	AD	Focal adhesion	67/2092	203/8465	4.40e-03	2.17e-02	1.38e-02	67
hsa052052	Colorectum	SER	Proteoglycans in cancer	58/1580	205/8465	4.37e-04	3.82e-03	2.77e-03	58
hsa048102	Colorectum	SER	Regulation of actin cytoskeleton	60/1580	229/8465	2.74e-03	2.02e-02	1.47e-02	60
hsa052053	Colorectum	SER	Proteoglycans in cancer	58/1580	205/8465	4.37e-04	3.82e-03	2.77e-03	58
hsa048103	Colorectum	SER	Regulation of actin cytoskeleton	60/1580	229/8465	2.74e-03	2.02e-02	1.47e-02	60
hsa052054	Colorectum	MSS	Proteoglycans in cancer	65/1875	205/8465	8.66e-04	5.38e-03	3.29e-03	65
hsa048104	Colorectum	MSS	Regulation of actin cytoskeleton	68/1875	229/8465	4.27e-03	1.86e-02	1.14e-02	68

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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

PPP1R12B

SNV

Missense_Mutation

novel

c.754A>G

p.Thr252Ala

p.T252A

protein_coding

deleterious(0.02)

probably_damaging(0.999)

TCGA-A2-A1G4-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

adriamycin

PPP1R12B

SNV

Missense_Mutation

novel

c.754A>G

p.Thr252Ala

p.T252A

protein_coding

deleterious(0.02)

probably_damaging(0.999)

TCGA-A8-A06R-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

PPP1R12B

SNV

Missense_Mutation

novel

c.754N>G

p.Thr252Ala

p.T252A

protein_coding

deleterious(0.02)

probably_damaging(0.999)

TCGA-A8-A096-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PPP1R12B

SNV

Missense_Mutation

rs368051793

c.926G>A

p.Arg309Gln

p.R309Q

protein_coding

deleterious(0.03)

benign(0.412)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PPP1R12B

SNV

Missense_Mutation

novel

c.2111N>A

p.Arg704Gln

p.R704Q

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

PPP1R12B

SNV

Missense_Mutation

novel

c.754N>G

p.Thr252Ala

p.T252A

protein_coding

deleterious(0.02)

probably_damaging(0.999)

TCGA-C8-A273-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

PPP1R12B

SNV

Missense_Mutation

novel

c.754N>G

p.Thr252Ala

p.T252A

protein_coding

deleterious(0.02)

probably_damaging(0.999)

TCGA-D8-A1XG-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

PPP1R12B

SNV

Missense_Mutation

novel

c.754N>G

p.Thr252Ala

p.T252A

protein_coding

deleterious(0.02)

probably_damaging(0.999)

TCGA-D8-A1Y1-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

PPP1R12B

SNV

Missense_Mutation

c.1639N>C

p.Ser547Pro

p.S547P

protein_coding

tolerated(0.07)

benign(0.026)

TCGA-E2-A1IF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

PPP1R12B

insertion

Frame_Shift_Ins

novel

c.465_466insAGTGATCTGCCCACCTCAGCCTCCCAAAG

p.Glu156SerfsTer24

p.E156Sfs*24

protein_coding

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

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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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