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: PIBF1

Gene summary for PIBF1

Gene summary.

Gene information	Species	Human
	Gene symbol	PIBF1
	Gene ID	10464
	Gene name	progesterone immunomodulatory binding factor 1
	Gene Alias	C13orf24
	Cytomap	13q21.33-q22.1
	Gene Type	protein-coding
	GO ID	GO:0000070
	UniProtAcc	Q8WXW3

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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
10464	PIBF1	CCI_1	Human	Cervix	CC	8.76e-06	7.18e-01	0.528
10464	PIBF1	CCI_2	Human	Cervix	CC	1.68e-08	9.02e-01	0.5249
10464	PIBF1	CCI_3	Human	Cervix	CC	4.58e-13	8.66e-01	0.516
10464	PIBF1	HTA11_3410_2000001011	Human	Colorectum	AD	1.31e-18	-6.02e-01	0.0155
10464	PIBF1	HTA11_347_2000001011	Human	Colorectum	AD	1.69e-03	4.35e-01	-0.1954
10464	PIBF1	HTA11_3361_2000001011	Human	Colorectum	AD	1.50e-06	-5.60e-01	-0.1207
10464	PIBF1	HTA11_5212_2000001011	Human	Colorectum	AD	1.31e-02	-6.59e-01	-0.2061
10464	PIBF1	HTA11_866_3004761011	Human	Colorectum	AD	4.05e-03	-4.12e-01	0.096
10464	PIBF1	HTA11_7696_3000711011	Human	Colorectum	AD	5.70e-04	-3.33e-01	0.0674
10464	PIBF1	HTA11_99999970781_79442	Human	Colorectum	MSS	1.19e-04	-3.56e-01	0.294
10464	PIBF1	HTA11_99999965104_69814	Human	Colorectum	MSS	2.62e-07	7.72e-01	0.281
10464	PIBF1	A001-C-207	Human	Colorectum	FAP	1.00e-03	-1.55e-01	0.1278
10464	PIBF1	A015-C-203	Human	Colorectum	FAP	1.21e-33	-4.51e-01	-0.1294
10464	PIBF1	A015-C-204	Human	Colorectum	FAP	6.22e-07	-2.77e-01	-0.0228
10464	PIBF1	A014-C-040	Human	Colorectum	FAP	6.22e-06	-3.44e-01	-0.1184
10464	PIBF1	A002-C-201	Human	Colorectum	FAP	3.21e-17	-2.84e-01	0.0324
10464	PIBF1	A001-C-119	Human	Colorectum	FAP	7.36e-10	-4.60e-01	-0.1557
10464	PIBF1	A001-C-108	Human	Colorectum	FAP	1.86e-17	-2.78e-01	-0.0272
10464	PIBF1	A002-C-205	Human	Colorectum	FAP	1.33e-28	-3.64e-01	-0.1236
10464	PIBF1	A001-C-104	Human	Colorectum	FAP	1.61e-02	-1.07e-01	0.0184

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
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:003367410	Cervix	CC	positive regulation of kinase activity	101/2311	467/18723	8.66e-09	7.22e-07	101
GO:00026837	Cervix	CC	negative regulation of immune system process	94/2311	434/18723	2.63e-08	1.87e-06	94
GO:00458608	Cervix	CC	positive regulation of protein kinase activity	85/2311	386/18723	5.61e-08	3.29e-06	85
GO:00018197	Cervix	CC	positive regulation of cytokine production	95/2311	467/18723	4.88e-07	1.85e-05	95
GO:004593610	Cervix	CC	negative regulation of phosphate metabolic process	88/2311	441/18723	2.92e-06	8.27e-05	88
GO:001056310	Cervix	CC	negative regulation of phosphorus metabolic process	88/2311	442/18723	3.21e-06	8.77e-05	88
GO:004232610	Cervix	CC	negative regulation of phosphorylation	77/2311	385/18723	1.09e-05	2.38e-04	77
GO:0051250	Cervix	CC	negative regulation of lymphocyte activation	39/2311	157/18723	1.23e-05	2.57e-04	39
GO:000193310	Cervix	CC	negative regulation of protein phosphorylation	69/2311	342/18723	2.29e-05	4.01e-04	69
GO:00516567	Cervix	CC	establishment of organelle localization	76/2311	390/18723	3.17e-05	5.21e-04	76
GO:0002695	Cervix	CC	negative regulation of leukocyte activation	43/2311	187/18723	3.47e-05	5.60e-04	43
GO:0050866	Cervix	CC	negative regulation of cell activation	44/2311	210/18723	2.76e-04	3.02e-03	44
GO:00464564	Cervix	CC	icosanoid biosynthetic process	15/2311	56/18723	2.60e-03	1.80e-02	15
GO:01400143	Cervix	CC	mitotic nuclear division	50/2311	287/18723	7.27e-03	3.91e-02	50
GO:00482851	Cervix	CC	organelle fission	78/2311	488/18723	9.70e-03	4.79e-02	78
GO:00015165	Cervix	CC	prostaglandin biosynthetic process	9/2311	31/18723	1.04e-02	4.97e-02	9
GO:00464575	Cervix	CC	prostanoid biosynthetic process	9/2311	31/18723	1.04e-02	4.97e-02	9
GO:0051656	Colorectum	AD	establishment of organelle localization	131/3918	390/18723	3.00e-09	2.06e-07	131
GO:0010563	Colorectum	AD	negative regulation of phosphorus metabolic process	130/3918	442/18723	1.26e-05	2.76e-04	130
GO:0045936	Colorectum	AD	negative regulation of phosphate metabolic process	129/3918	441/18723	1.81e-05	3.76e-04	129

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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

PIBF1

SNV

Missense_Mutation

c.601N>G

p.Leu201Val

p.L201V

Q8WXW3

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PIBF1

SNV

Missense_Mutation

novel

c.1066N>A

p.Glu356Lys

p.E356K

Q8WXW3

protein_coding

deleterious(0.01)

probably_damaging(0.994)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PIBF1

insertion

Frame_Shift_Ins

novel

c.1669_1670insT

p.Ser559PhefsTer7

p.S559Ffs*7

Q8WXW3

protein_coding

TCGA-AN-A0XW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

PIBF1

insertion

Nonsense_Mutation

novel

c.1707_1708insAAACCTAACATGATATGAT

p.Ala570LysfsTer6

p.A570Kfs*6

Q8WXW3

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

PIBF1

insertion

In_Frame_Ins

novel

c.1709_1710insAAT

p.Ala570_Lys571insIle

p.A570_K571insI

Q8WXW3

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

PIBF1

insertion

In_Frame_Ins

novel

c.238_239insTTACTCACAGGAACCCTCTCCCGA

p.Asp80delinsValThrHisArgAsnProLeuProAsn

p.D80delinsVTHRNPLPN

Q8WXW3

protein_coding

TCGA-B6-A0I8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PIBF1

insertion

Nonsense_Mutation

novel

c.1160_1161insTTTTGCAATCCTTTCAAAGCTCAGAAATAATTAATAGT

p.Lys387AsnfsTer12

p.K387Nfs*12

Q8WXW3

protein_coding

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

PIBF1

SNV

Missense_Mutation

novel

c.2041C>A

p.His681Asn

p.H681N

Q8WXW3

protein_coding

tolerated(0.08)

probably_damaging(0.979)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PIBF1

SNV

Missense_Mutation

novel

c.1748G>C

p.Arg583Thr

p.R583T

Q8WXW3

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-4J-AA1J-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PIBF1

SNV

Missense_Mutation

c.97G>A

p.Asp33Asn

p.D33N

Q8WXW3

protein_coding

deleterious(0.01)

possibly_damaging(0.813)

TCGA-DG-A2KK-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

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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