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: C12orf57

Gene summary for C12ORF57

Gene summary.

Gene information	Species	Human
	Gene symbol	C12orf57
	Gene ID	113246
	Gene name	chromosome 12 open reading frame 57
	Gene Alias	C10
	Cytomap	12p13.31
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	Q99622

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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
113246	C12orf57	CA_HPV_1	Human	Cervix	CC	1.57e-14	-4.14e-01	0.0264
113246	C12orf57	CA_HPV_3	Human	Cervix	CC	5.84e-07	1.35e-01	0.0414
113246	C12orf57	CCI_1	Human	Cervix	CC	3.64e-12	-8.02e-01	0.528
113246	C12orf57	CCI_2	Human	Cervix	CC	1.60e-08	-6.95e-01	0.5249
113246	C12orf57	CCI_3	Human	Cervix	CC	2.77e-15	-7.91e-01	0.516
113246	C12orf57	CCII_1	Human	Cervix	CC	5.24e-22	-7.99e-01	0.3249
113246	C12orf57	sample3	Human	Cervix	CC	4.92e-02	-1.44e-01	0.1387
113246	C12orf57	H2	Human	Cervix	HSIL_HPV	3.75e-05	-4.11e-01	0.0632
113246	C12orf57	L1	Human	Cervix	CC	2.86e-06	-4.14e-01	0.0802
113246	C12orf57	T3	Human	Cervix	CC	4.96e-03	-1.18e-01	0.1389
113246	C12orf57	HTA11_3410_2000001011	Human	Colorectum	AD	2.68e-11	2.47e-01	0.0155
113246	C12orf57	HTA11_2487_2000001011	Human	Colorectum	SER	1.16e-12	4.40e-01	-0.1808
113246	C12orf57	HTA11_2951_2000001011	Human	Colorectum	AD	1.15e-05	3.67e-01	0.0216
113246	C12orf57	HTA11_1938_2000001011	Human	Colorectum	AD	4.30e-13	4.67e-01	-0.0811
113246	C12orf57	HTA11_78_2000001011	Human	Colorectum	AD	4.12e-02	9.98e-02	-0.1088
113246	C12orf57	HTA11_347_2000001011	Human	Colorectum	AD	4.13e-22	4.93e-01	-0.1954
113246	C12orf57	HTA11_411_2000001011	Human	Colorectum	SER	7.66e-12	8.05e-01	-0.2602
113246	C12orf57	HTA11_2112_2000001011	Human	Colorectum	SER	3.17e-11	8.17e-01	-0.2196
113246	C12orf57	HTA11_3361_2000001011	Human	Colorectum	AD	1.08e-10	4.43e-01	-0.1207
113246	C12orf57	HTA11_83_2000001011	Human	Colorectum	SER	1.66e-07	3.49e-01	-0.1526

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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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
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:00615647	Cervix	CC	axon development	89/2311	467/18723	1.71e-05	3.27e-04	89
GO:00074097	Cervix	CC	axonogenesis	78/2311	418/18723	1.14e-04	1.43e-03	78
GO:00097915	Cervix	CC	post-embryonic development	20/2311	80/18723	1.40e-03	1.10e-02	20
GO:00219541	Cervix	CC	central nervous system neuron development	19/2311	81/18723	3.96e-03	2.48e-02	19
GO:00309003	Cervix	CC	forebrain development	64/2311	379/18723	5.53e-03	3.19e-02	64
GO:0150063	Cervix	CC	visual system development	63/2311	375/18723	6.58e-03	3.65e-02	63
GO:00902578	Cervix	CC	regulation of muscle system process	45/2311	252/18723	6.73e-03	3.70e-02	45
GO:0001654	Cervix	CC	eye development	62/2311	371/18723	7.83e-03	4.13e-02	62
GO:0048880	Cervix	CC	sensory system development	63/2311	381/18723	9.29e-03	4.66e-02	63
GO:0007409	Colorectum	AD	axonogenesis	122/3918	418/18723	3.36e-05	6.15e-04	122
GO:0061564	Colorectum	AD	axon development	132/3918	467/18723	8.40e-05	1.31e-03	132
GO:0009791	Colorectum	AD	post-embryonic development	29/3918	80/18723	1.13e-03	1.03e-02	29
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:00615641	Colorectum	SER	axon development	94/2897	467/18723	3.78e-03	3.13e-02	94
GO:00097911	Colorectum	SER	post-embryonic development	22/2897	80/18723	4.12e-03	3.36e-02	22
GO:00074091	Colorectum	SER	axonogenesis	84/2897	418/18723	6.20e-03	4.49e-02	84
GO:00074092	Colorectum	MSS	axonogenesis	105/3467	418/18723	4.32e-04	5.23e-03	105
GO:00615642	Colorectum	MSS	axon development	115/3467	467/18723	5.33e-04	6.00e-03	115

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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

C12orf57

SNV

Missense_Mutation

c.160N>A

p.Val54Met

p.V54M

Q99622

protein_coding

deleterious(0.04)

benign(0.332)

TCGA-A2-A0CW-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

C12orf57

SNV

Missense_Mutation

rs782133839

c.291N>A

p.Ser97Arg

p.S97R

Q99622

protein_coding

tolerated(0.76)

benign(0.01)

TCGA-E2-A152-01

Breast

breast invasive carcinoma

Female

<65

I/II

Targeted Molecular therapy

trastuzumab

C12orf57

SNV

Missense_Mutation

rs782133839

c.291C>A

p.Ser97Arg

p.S97R

Q99622

protein_coding

tolerated(0.76)

benign(0.01)

TCGA-AA-3867-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Unknown

C12orf57

SNV

Missense_Mutation

novel

c.98C>T

p.Ala33Val

p.A33V

Q99622

protein_coding

tolerated(0.27)

benign(0.003)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

C12orf57

SNV

Missense_Mutation

novel

c.347G>T

p.Gly116Val

p.G116V

Q99622

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.778)

TCGA-AX-A2HA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

C12orf57

SNV

Missense_Mutation

c.42N>T

p.Glu14Asp

p.E14D

Q99622

protein_coding

tolerated(0.18)

probably_damaging(0.978)

TCGA-D1-A103-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

C12orf57

SNV

Missense_Mutation

novel

c.94A>C

p.Asn32His

p.N32H

Q99622

protein_coding

deleterious(0.02)

probably_damaging(0.957)

TCGA-EO-A22R-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

C12orf57

SNV

Missense_Mutation

rs374751929

c.373N>A

p.Ala125Thr

p.A125T

Q99622

protein_coding

tolerated_low_confidence(0.1)

benign(0.034)

TCGA-EO-A22U-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

C12orf57

SNV

Missense_Mutation

rs144915095

c.328A>G

p.Met110Val

p.M110V

Q99622

protein_coding

tolerated(0.84)

benign(0.015)

TCGA-PG-A917-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

C12orf57

SNV

Missense_Mutation

c.74N>T

p.Gln25Leu

p.Q25L

Q99622

protein_coding

tolerated(0.26)

benign(0.024)

TCGA-50-5930-01

Lung

lung adenocarcinoma

Male

<65

III/IV

Chemotherapy

taxotere

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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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