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: CPSF6

Gene summary for CPSF6

Gene summary.

Gene information	Species	Human
	Gene symbol	CPSF6
	Gene ID	11052
	Gene name	cleavage and polyadenylation specific factor 6
	Gene Alias	CFIM
	Cytomap	12q15
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	Q16630

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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
11052	CPSF6	LZE2T	Human	Esophagus	ESCC	1.96e-07	9.68e-01	0.082
11052	CPSF6	LZE4T	Human	Esophagus	ESCC	1.32e-18	5.64e-01	0.0811
11052	CPSF6	LZE7T	Human	Esophagus	ESCC	8.36e-10	7.60e-01	0.0667
11052	CPSF6	LZE8T	Human	Esophagus	ESCC	2.83e-15	4.37e-01	0.067
11052	CPSF6	LZE20T	Human	Esophagus	ESCC	2.89e-05	2.39e-01	0.0662
11052	CPSF6	LZE22D1	Human	Esophagus	HGIN	1.05e-03	1.06e-01	0.0595
11052	CPSF6	LZE22T	Human	Esophagus	ESCC	7.50e-05	5.42e-01	0.068
11052	CPSF6	LZE24T	Human	Esophagus	ESCC	6.03e-26	7.32e-01	0.0596
11052	CPSF6	LZE21T	Human	Esophagus	ESCC	4.22e-08	5.43e-01	0.0655
11052	CPSF6	LZE6T	Human	Esophagus	ESCC	1.44e-08	4.10e-01	0.0845
11052	CPSF6	P1T-E	Human	Esophagus	ESCC	1.03e-14	6.95e-01	0.0875
11052	CPSF6	P2T-E	Human	Esophagus	ESCC	1.27e-85	1.52e+00	0.1177
11052	CPSF6	P4T-E	Human	Esophagus	ESCC	1.31e-39	8.87e-01	0.1323
11052	CPSF6	P5T-E	Human	Esophagus	ESCC	2.16e-36	7.82e-01	0.1327
11052	CPSF6	P8T-E	Human	Esophagus	ESCC	7.79e-56	8.53e-01	0.0889
11052	CPSF6	P9T-E	Human	Esophagus	ESCC	4.26e-24	5.75e-01	0.1131
11052	CPSF6	P10T-E	Human	Esophagus	ESCC	1.28e-55	8.99e-01	0.116
11052	CPSF6	P11T-E	Human	Esophagus	ESCC	7.73e-18	7.15e-01	0.1426
11052	CPSF6	P12T-E	Human	Esophagus	ESCC	5.87e-49	8.48e-01	0.1122
11052	CPSF6	P15T-E	Human	Esophagus	ESCC	3.29e-45	9.80e-01	0.1149

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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
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
Prostate		BPH: Benign Prostatic Hyperplasia
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:002261327	Esophagus	HGIN	ribonucleoprotein complex biogenesis	158/2587	463/18723	2.61e-29	5.23e-26	158
GO:007182627	Esophagus	HGIN	ribonucleoprotein complex subunit organization	84/2587	227/18723	1.34e-18	5.37e-16	84
GO:002261827	Esophagus	HGIN	ribonucleoprotein complex assembly	82/2587	220/18723	2.07e-18	7.36e-16	82
GO:190331120	Esophagus	HGIN	regulation of mRNA metabolic process	91/2587	288/18723	5.06e-15	9.78e-13	91
GO:005068419	Esophagus	HGIN	regulation of mRNA processing	55/2587	137/18723	2.17e-14	3.94e-12	55
GO:000640320	Esophagus	HGIN	RNA localization	66/2587	201/18723	4.06e-12	5.41e-10	66
GO:000691319	Esophagus	HGIN	nucleocytoplasmic transport	83/2587	301/18723	2.14e-10	1.97e-08	83
GO:005116919	Esophagus	HGIN	nuclear transport	83/2587	301/18723	2.14e-10	1.97e-08	83
GO:005116819	Esophagus	HGIN	nuclear export	48/2587	154/18723	2.21e-08	1.34e-06	48
GO:005065716	Esophagus	HGIN	nucleic acid transport	49/2587	163/18723	5.71e-08	3.06e-06	49
GO:005065816	Esophagus	HGIN	RNA transport	49/2587	163/18723	5.71e-08	3.06e-06	49
GO:005123616	Esophagus	HGIN	establishment of RNA localization	49/2587	166/18723	1.07e-07	5.47e-06	49
GO:004682219	Esophagus	HGIN	regulation of nucleocytoplasmic transport	35/2587	106/18723	3.69e-07	1.69e-05	35
GO:003238617	Esophagus	HGIN	regulation of intracellular transport	79/2587	337/18723	1.11e-06	4.36e-05	79
GO:001593116	Esophagus	HGIN	nucleobase-containing compound transport	57/2587	222/18723	1.76e-06	6.52e-05	57
GO:004682416	Esophagus	HGIN	positive regulation of nucleocytoplasmic transport	23/2587	62/18723	3.94e-06	1.32e-04	23
GO:003238820	Esophagus	HGIN	positive regulation of intracellular transport	51/2587	202/18723	1.00e-05	2.92e-04	51
GO:00064056	Esophagus	HGIN	RNA export from nucleus	23/2587	84/18723	7.90e-04	1.03e-02	23
GO:00311243	Esophagus	HGIN	mRNA 3'-end processing	18/2587	62/18723	1.37e-03	1.61e-02	18
GO:00314404	Esophagus	HGIN	regulation of mRNA 3'-end processing	10/2587	28/18723	3.04e-03	2.88e-02	10

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa030159	Esophagus	HGIN	mRNA surveillance pathway	30/1383	97/8465	2.48e-04	2.69e-03	2.14e-03	30
hsa0301514	Esophagus	HGIN	mRNA surveillance pathway	30/1383	97/8465	2.48e-04	2.69e-03	2.14e-03	30
hsa032509	Esophagus	ESCC	Viral life cycle - HIV-1	54/4205	63/8465	2.01e-09	2.17e-08	1.11e-08	54
hsa0301524	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa0325014	Esophagus	ESCC	Viral life cycle - HIV-1	54/4205	63/8465	2.01e-09	2.17e-08	1.11e-08	54
hsa0301534	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa0301521	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa032502	Liver	HCC	Viral life cycle - HIV-1	46/4020	63/8465	3.25e-05	1.88e-04	1.04e-04	46
hsa0301531	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa0325011	Liver	HCC	Viral life cycle - HIV-1	46/4020	63/8465	3.25e-05	1.88e-04	1.04e-04	46
hsa030158	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa032508	Oral cavity	OSCC	Viral life cycle - HIV-1	45/3704	63/8465	7.62e-06	3.59e-05	1.83e-05	45
hsa0301513	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa0325013	Oral cavity	OSCC	Viral life cycle - HIV-1	45/3704	63/8465	7.62e-06	3.59e-05	1.83e-05	45
hsa0301523	Oral cavity	LP	mRNA surveillance pathway	50/2418	97/8465	1.39e-06	1.50e-05	9.66e-06	50
hsa0325022	Oral cavity	LP	Viral life cycle - HIV-1	32/2418	63/8465	1.55e-04	9.08e-04	5.86e-04	32
hsa0301533	Oral cavity	LP	mRNA surveillance pathway	50/2418	97/8465	1.39e-06	1.50e-05	9.66e-06	50
hsa0325031	Oral cavity	LP	Viral life cycle - HIV-1	32/2418	63/8465	1.55e-04	9.08e-04	5.86e-04	32
hsa0301541	Oral cavity	EOLP	mRNA surveillance pathway	30/1218	97/8465	2.26e-05	1.20e-04	7.07e-05	30
hsa0325041	Oral cavity	EOLP	Viral life cycle - HIV-1	16/1218	63/8465	1.46e-02	3.77e-02	2.22e-02	16

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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

CPSF6

SNV

Missense_Mutation

c.1589N>A

p.Arg530Gln

p.R530Q

Q16630

protein_coding

deleterious(0.02)

probably_damaging(0.947)

TCGA-A8-A09G-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

CPSF6

SNV

Missense_Mutation

c.1762N>T

p.Arg588Cys

p.R588C

Q16630

protein_coding

deleterious_low_confidence(0)

benign(0.003)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CPSF6

SNV

Missense_Mutation

c.1735N>T

p.Arg579Cys

p.R579C

Q16630

protein_coding

deleterious_low_confidence(0)

benign(0.003)

TCGA-D8-A1JN-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozolum

CPSF6

SNV

Missense_Mutation

c.1552N>C

p.Glu518Gln

p.E518Q

Q16630

protein_coding

tolerated(0.08)

possibly_damaging(0.78)

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

CPSF6

deletion

Frame_Shift_Del

c.326delN

p.Leu110TrpfsTer3

p.L110Wfs*3

Q16630

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

CPSF6

insertion

Frame_Shift_Ins

novel

c.1108_1109insTTAAGGTT

p.Pro370LeufsTer8

p.P370Lfs*8

Q16630

protein_coding

TCGA-B6-A0IN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CPSF6

insertion

Nonsense_Mutation

novel

c.1717_1718insAAGGCATTTGCAAGTTAATATATTAGAAATA

p.Arg573GlnfsTer9

p.R573Qfs*9

Q16630

protein_coding

TCGA-BH-A0H0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

CPSF6

SNV

Missense_Mutation

novel

c.404C>T

p.Ala135Val

p.A135V

Q16630

protein_coding

tolerated(0.12)

benign(0.217)

TCGA-JW-AAVH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CPSF6

SNV

Missense_Mutation

c.1595N>C

p.Arg532Thr

p.R532T

Q16630

protein_coding

deleterious(0)

probably_damaging(0.978)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CPSF6

SNV

Missense_Mutation

c.1072N>T

p.Gly358Cys

p.G358C

Q16630

protein_coding

tolerated(0.19)

probably_damaging(0.917)

TCGA-A6-6653-01

Colorectum

colon adenocarcinoma

Male

>=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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