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: TMEM258

Gene summary for TMEM258

Gene summary.

Gene information	Species	Human
	Gene symbol	TMEM258
	Gene ID	746
	Gene name	transmembrane protein 258
	Gene Alias	C11orf10
	Cytomap	11q12.2
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	P61165

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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
746	TMEM258	P10	Human	Prostate	Tumor	3.42e-06	2.71e-01	-0.0902
746	TMEM258	GSM5353221_PA_PB2A_Pool_1_3_S25_L001	Human	Prostate	Tumor	4.86e-04	-4.79e-01	0.1633
746	TMEM258	GSM5353222_PA_PB2B_Pool_1_3_S52_L002	Human	Prostate	Tumor	1.13e-12	-6.23e-01	0.1608
746	TMEM258	GSM5353223_PA_PB2B_Pool_2_S26_L001	Human	Prostate	Tumor	8.12e-05	-4.98e-01	0.1604
746	TMEM258	GSM5353225_PA_PR5196-1_Pool_1_2_3_S53_L002	Human	Prostate	Tumor	3.88e-07	-7.78e-01	0.1619
746	TMEM258	GSM5353227_PA_PR5199-193K_Pool_1_2_3_S55_L002	Human	Prostate	Tumor	1.55e-07	-5.82e-01	0.1602
746	TMEM258	GSM5353232_PA_PR5249_T1_S3_L001	Human	Prostate	Tumor	3.48e-09	-6.78e-01	0.1439
746	TMEM258	GSM5353240_PA_PR5254_T1_S15_L001	Human	Prostate	Tumor	3.72e-15	-5.23e-01	0.1575
746	TMEM258	GSM5353243_PA_PR5261_T1_S23_L002	Human	Prostate	Tumor	5.64e-32	-7.36e-01	0.1545
746	TMEM258	GSM5353244_PA_PR5261_T2_S24_L002	Human	Prostate	Tumor	2.01e-21	-7.51e-01	0.1569
746	TMEM258	GSM5353247_PA_PR5269_3_S27_L002	Human	Prostate	Tumor	4.74e-03	-8.73e-01	0.1532
746	TMEM258	GSM5353248_PA_PR5269_4_S28_L002	Human	Prostate	Tumor	4.49e-02	-6.75e-01	0.1541
746	TMEM258	P4_S8_cSCC	Human	Skin	cSCC	2.46e-08	-1.42e-01	-0.3095
746	TMEM258	P5_S10_cSCC	Human	Skin	cSCC	4.15e-09	3.92e-02	-0.299
746	TMEM258	P1_cSCC	Human	Skin	cSCC	1.59e-53	1.98e+00	0.0292
746	TMEM258	P2_cSCC	Human	Skin	cSCC	6.19e-37	1.36e+00	-0.024
746	TMEM258	P4_cSCC	Human	Skin	cSCC	1.53e-48	1.25e+00	-0.00290000000000005
746	TMEM258	P10_cSCC	Human	Skin	cSCC	4.37e-52	1.75e+00	0.1017
746	TMEM258	cSCC_p4	Human	Skin	cSCC	7.13e-05	-6.63e-02	-0.2022
746	TMEM258	cSCC_p8	Human	Skin	cSCC	3.03e-04	-8.86e-02	-0.1971

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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
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:0006487	Colorectum	AD	protein N-linked glycosylation	25/3918	65/18723	9.12e-04	8.71e-03	25
GO:0006486	Colorectum	AD	protein glycosylation	64/3918	226/18723	4.86e-03	3.27e-02	64
GO:0043413	Colorectum	AD	macromolecule glycosylation	64/3918	226/18723	4.86e-03	3.27e-02	64
GO:0070085	Colorectum	AD	glycosylation	67/3918	240/18723	5.78e-03	3.67e-02	67
GO:00064871	Colorectum	MSS	protein N-linked glycosylation	23/3467	65/18723	9.47e-04	9.54e-03	23
GO:00064876	Esophagus	HGIN	protein N-linked glycosylation	17/2587	65/18723	6.04e-03	4.87e-02	17
GO:000648714	Esophagus	ESCC	protein N-linked glycosylation	51/8552	65/18723	6.41e-08	1.13e-06	51
GO:00091002	Esophagus	ESCC	glycoprotein metabolic process	226/8552	387/18723	2.64e-07	3.94e-06	226
GO:00700854	Esophagus	ESCC	glycosylation	144/8552	240/18723	5.12e-06	5.38e-05	144
GO:00064865	Esophagus	ESCC	protein glycosylation	135/8552	226/18723	1.36e-05	1.24e-04	135
GO:00434135	Esophagus	ESCC	macromolecule glycosylation	135/8552	226/18723	1.36e-05	1.24e-04	135
GO:00091012	Esophagus	ESCC	glycoprotein biosynthetic process	181/8552	317/18723	2.54e-05	2.15e-04	181
GO:00064873	Liver	Cirrhotic	protein N-linked glycosylation	30/4634	65/18723	1.40e-04	1.36e-03	30
GO:000648711	Liver	HCC	protein N-linked glycosylation	48/7958	65/18723	2.85e-07	5.00e-06	48
GO:00064862	Liver	HCC	protein glycosylation	122/7958	226/18723	3.11e-04	2.21e-03	122
GO:00434132	Liver	HCC	macromolecule glycosylation	122/7958	226/18723	3.11e-04	2.21e-03	122
GO:00700852	Liver	HCC	glycosylation	128/7958	240/18723	4.35e-04	2.92e-03	128
GO:0009100	Liver	HCC	glycoprotein metabolic process	193/7958	387/18723	1.89e-03	9.62e-03	193
GO:00064863	Lung	AIS	protein glycosylation	35/1849	226/18723	4.93e-03	4.27e-02	35
GO:00434133	Lung	AIS	macromolecule glycosylation	35/1849	226/18723	4.93e-03	4.27e-02	35

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414120	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa04141110	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa0414144	Cervix	N_HPV	Protein processing in endoplasmic reticulum	21/349	174/8465	8.84e-06	1.09e-04	8.55e-05	21
hsa0414154	Cervix	N_HPV	Protein processing in endoplasmic reticulum	21/349	174/8465	8.84e-06	1.09e-04	8.55e-05	21
hsa04141	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa00510	Colorectum	AD	N-Glycan biosynthesis	21/2092	53/8465	1.15e-02	4.24e-02	2.71e-02	21
hsa041411	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa005101	Colorectum	AD	N-Glycan biosynthesis	21/2092	53/8465	1.15e-02	4.24e-02	2.71e-02	21
hsa041412	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
hsa041413	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
hsa041414	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa005102	Colorectum	MSS	N-Glycan biosynthesis	20/1875	53/8465	7.17e-03	2.83e-02	1.73e-02	20
hsa00513	Colorectum	MSS	Various types of N-glycan biosynthesis	16/1875	42/8465	1.39e-02	4.53e-02	2.77e-02	16
hsa041415	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa005103	Colorectum	MSS	N-Glycan biosynthesis	20/1875	53/8465	7.17e-03	2.83e-02	1.73e-02	20
hsa005131	Colorectum	MSS	Various types of N-glycan biosynthesis	16/1875	42/8465	1.39e-02	4.53e-02	2.77e-02	16
hsa041416	Colorectum	MSI-H	Protein processing in endoplasmic reticulum	46/797	174/8465	4.53e-11	9.78e-10	8.19e-10	46
hsa041417	Colorectum	MSI-H	Protein processing in endoplasmic reticulum	46/797	174/8465	4.53e-11	9.78e-10	8.19e-10	46
hsa0414126	Endometrium	AEH	Protein processing in endoplasmic reticulum	62/1197	174/8465	5.97e-13	1.39e-11	1.01e-11	62
hsa04141111	Endometrium	AEH	Protein processing in endoplasmic reticulum	62/1197	174/8465	5.97e-13	1.39e-11	1.01e-11	62

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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

TMEM258

insertion

Nonsense_Mutation

novel

c.159_160insTCCCTGCCATAAACATAGCCACCATT

p.Leu54SerfsTer4

p.L54Sfs*4

P61165

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

TMEM258

SNV

Missense_Mutation

c.227G>A

p.Gly76Asp

p.G76D

P61165

protein_coding

deleterious(0.02)

probably_damaging(0.989)

TCGA-BG-A0M0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

TMEM258

SNV

Missense_Mutation

c.93N>A

p.Phe31Leu

p.F31L

P61165

protein_coding

tolerated(0.2)

benign(0.04)

TCGA-BS-A0UV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

TMEM258

SNV

Missense_Mutation

novel

c.137N>G

p.Tyr46Cys

p.Y46C

P61165

protein_coding

tolerated(0.1)

benign(0.013)

TCGA-55-8089-01

Lung

lung adenocarcinoma

Male

<65

I/II

Unknown

TMEM258

SNV

Missense_Mutation

rs764740554

c.67N>A

p.Val23Met

p.V23M

P61165

protein_coding

tolerated(0.29)

benign(0.058)

TCGA-CV-5970-01

Oral cavity

head & neck squamous cell carcinoma

Male

<65

I/II

Unknown

TMEM258

SNV

Missense_Mutation

c.112N>A

p.Val38Ile

p.V38I

P61165

protein_coding

tolerated(0.66)

benign(0.112)

TCGA-HU-A4GQ-01

Stomach

stomach adenocarcinoma

Male

>=65

III/IV

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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