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: NACA

Gene summary for NACA

Gene summary.

Gene information	Species	Human
	Gene symbol	NACA
	Gene ID	4666
	Gene name	nascent polypeptide associated complex subunit alpha
	Gene Alias	HSD48
	Cytomap	12q13.3
	Gene Type	protein-coding
	GO ID	GO:0006605
	UniProtAcc	A0A024RB41

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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
4666	NACA	GSM4909281	Human	Breast	IDC	6.97e-56	-4.74e-01	0.21
4666	NACA	GSM4909282	Human	Breast	IDC	3.07e-28	-2.83e-01	-0.0288
4666	NACA	GSM4909285	Human	Breast	IDC	1.23e-30	2.49e-01	0.21
4666	NACA	GSM4909286	Human	Breast	IDC	2.82e-14	-1.59e-01	0.1081
4666	NACA	GSM4909287	Human	Breast	IDC	6.03e-33	-4.79e-01	0.2057
4666	NACA	GSM4909290	Human	Breast	IDC	3.42e-15	-3.00e-01	0.2096
4666	NACA	GSM4909291	Human	Breast	IDC	4.40e-14	-2.82e-01	0.1753
4666	NACA	GSM4909293	Human	Breast	IDC	1.56e-05	-5.93e-02	0.1581
4666	NACA	GSM4909294	Human	Breast	IDC	6.91e-18	1.61e-01	0.2022
4666	NACA	GSM4909295	Human	Breast	IDC	4.29e-30	-7.02e-01	0.0898
4666	NACA	GSM4909296	Human	Breast	IDC	5.98e-09	-2.21e-01	0.1524
4666	NACA	GSM4909297	Human	Breast	IDC	3.85e-13	-3.09e-01	0.1517
4666	NACA	GSM4909298	Human	Breast	IDC	2.93e-04	-8.93e-02	0.1551
4666	NACA	GSM4909299	Human	Breast	IDC	1.24e-11	-1.64e-01	0.035
4666	NACA	GSM4909301	Human	Breast	IDC	2.95e-48	-4.45e-01	0.1577
4666	NACA	GSM4909302	Human	Breast	IDC	6.13e-22	-3.68e-01	0.1545
4666	NACA	GSM4909304	Human	Breast	IDC	8.60e-40	-2.80e-01	0.1636
4666	NACA	GSM4909307	Human	Breast	IDC	7.33e-10	-1.73e-01	0.1569
4666	NACA	GSM4909308	Human	Breast	IDC	6.36e-10	-1.43e-01	0.158
4666	NACA	GSM4909309	Human	Breast	IDC	1.53e-06	-2.40e-01	0.0483

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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:00066059	Breast	Precancer	protein targeting	33/1080	314/18723	6.50e-04	7.99e-03	33
GO:000660514	Breast	IDC	protein targeting	43/1434	314/18723	1.44e-04	2.53e-03	43
GO:000660523	Breast	DCIS	protein targeting	43/1390	314/18723	7.17e-05	1.41e-03	43
GO:000660510	Cervix	CC	protein targeting	68/2311	314/18723	2.17e-06	6.55e-05	68
GO:00901509	Cervix	CC	establishment of protein localization to membrane	54/2311	260/18723	7.67e-05	1.05e-03	54
GO:0090150	Colorectum	AD	establishment of protein localization to membrane	100/3918	260/18723	6.01e-11	6.33e-09	100
GO:0006605	Colorectum	AD	protein targeting	105/3918	314/18723	1.39e-07	6.44e-06	105
GO:00901501	Colorectum	SER	establishment of protein localization to membrane	68/2897	260/18723	5.55e-06	2.01e-04	68
GO:00066051	Colorectum	SER	protein targeting	76/2897	314/18723	3.19e-05	8.47e-04	76
GO:00901502	Colorectum	MSS	establishment of protein localization to membrane	90/3467	260/18723	4.11e-10	3.49e-08	90
GO:00066052	Colorectum	MSS	protein targeting	97/3467	314/18723	6.76e-08	3.46e-06	97
GO:00066053	Colorectum	MSI-H	protein targeting	44/1319	314/18723	9.50e-06	4.55e-04	44
GO:00901503	Colorectum	MSI-H	establishment of protein localization to membrane	32/1319	260/18723	1.47e-03	2.23e-02	32
GO:00901504	Colorectum	FAP	establishment of protein localization to membrane	69/2622	260/18723	6.40e-08	4.54e-06	69
GO:00066054	Colorectum	FAP	protein targeting	74/2622	314/18723	3.21e-06	1.17e-04	74
GO:0006612	Colorectum	FAP	protein targeting to membrane	30/2622	131/18723	3.95e-03	2.75e-02	30
GO:00901505	Colorectum	CRC	establishment of protein localization to membrane	51/2078	260/18723	3.59e-05	9.05e-04	51
GO:00066055	Colorectum	CRC	protein targeting	54/2078	314/18723	7.17e-04	9.28e-03	54
GO:000660516	Endometrium	AEH	protein targeting	68/2100	314/18723	6.30e-08	3.38e-06	68
GO:009015010	Endometrium	AEH	establishment of protein localization to membrane	51/2100	260/18723	4.74e-05	7.85e-04	51

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0492812	Cervix	CC	Parathyroid hormone synthesis, secretion and action	27/1267	106/8465	3.12e-03	1.19e-02	7.03e-03	27
hsa0492813	Cervix	CC	Parathyroid hormone synthesis, secretion and action	27/1267	106/8465	3.12e-03	1.19e-02	7.03e-03	27
hsa04928	Colorectum	AD	Parathyroid hormone synthesis, secretion and action	38/2092	106/8465	6.60e-03	2.77e-02	1.76e-02	38
hsa049281	Colorectum	AD	Parathyroid hormone synthesis, secretion and action	38/2092	106/8465	6.60e-03	2.77e-02	1.76e-02	38
hsa049282	Colorectum	SER	Parathyroid hormone synthesis, secretion and action	31/1580	106/8465	5.20e-03	3.28e-02	2.38e-02	31
hsa049283	Colorectum	SER	Parathyroid hormone synthesis, secretion and action	31/1580	106/8465	5.20e-03	3.28e-02	2.38e-02	31
hsa049284	Colorectum	MSS	Parathyroid hormone synthesis, secretion and action	37/1875	106/8465	1.72e-03	9.13e-03	5.59e-03	37
hsa049285	Colorectum	MSS	Parathyroid hormone synthesis, secretion and action	37/1875	106/8465	1.72e-03	9.13e-03	5.59e-03	37
hsa049286	Colorectum	FAP	Parathyroid hormone synthesis, secretion and action	29/1404	106/8465	3.37e-03	1.44e-02	8.77e-03	29
hsa049287	Colorectum	FAP	Parathyroid hormone synthesis, secretion and action	29/1404	106/8465	3.37e-03	1.44e-02	8.77e-03	29
hsa049288	Colorectum	CRC	Parathyroid hormone synthesis, secretion and action	24/1091	106/8465	3.71e-03	2.29e-02	1.55e-02	24
hsa049289	Colorectum	CRC	Parathyroid hormone synthesis, secretion and action	24/1091	106/8465	3.71e-03	2.29e-02	1.55e-02	24
hsa0492816	Esophagus	ESCC	Parathyroid hormone synthesis, secretion and action	66/4205	106/8465	5.86e-03	1.47e-02	7.51e-03	66
hsa0492817	Esophagus	ESCC	Parathyroid hormone synthesis, secretion and action	66/4205	106/8465	5.86e-03	1.47e-02	7.51e-03	66
hsa0492810	Lung	IAC	Parathyroid hormone synthesis, secretion and action	26/1053	106/8465	4.34e-04	4.03e-03	2.68e-03	26
hsa0492811	Lung	IAC	Parathyroid hormone synthesis, secretion and action	26/1053	106/8465	4.34e-04	4.03e-03	2.68e-03	26
hsa0492821	Lung	AIS	Parathyroid hormone synthesis, secretion and action	22/961	106/8465	3.45e-03	1.90e-02	1.21e-02	22
hsa0492831	Lung	AIS	Parathyroid hormone synthesis, secretion and action	22/961	106/8465	3.45e-03	1.90e-02	1.21e-02	22
hsa0492841	Lung	MIAC	Parathyroid hormone synthesis, secretion and action	17/507	106/8465	1.69e-04	3.51e-03	2.54e-03	17
hsa0492851	Lung	MIAC	Parathyroid hormone synthesis, secretion and action	17/507	106/8465	1.69e-04	3.51e-03	2.54e-03	17

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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

NACA

SNV

Missense_Mutation

c.263G>C

p.Gly88Ala

p.G88A

E9PAV3

protein_coding

deleterious_low_confidence(0.01)

benign(0.14)

TCGA-A2-A04W-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

NACA

SNV

Missense_Mutation

c.64N>A

p.Glu22Lys

p.E22K

E9PAV3

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.997)

TCGA-A8-A06P-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unspecific

NACA

SNV

Missense_Mutation

c.1059N>C

p.Gln353His

p.Q353H

E9PAV3

protein_coding

deleterious_low_confidence(0)

benign(0.021)

TCGA-BH-A18T-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NACA

SNV

Missense_Mutation

c.563T>C

p.Leu188Pro

p.L188P

E9PAV3

protein_coding

tolerated_low_confidence(1)

benign(0)

TCGA-C8-A135-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

NACA

SNV

Missense_Mutation

novel

c.1534N>A

p.Pro512Thr

p.P512T

E9PAV3

protein_coding

tolerated_low_confidence(0.23)

benign(0.001)

TCGA-E2-A15T-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

NACA

insertion

Frame_Shift_Ins

novel

c.1953_1954insATTATTTGCCTGTGCCAAGAAACAAAGACCTTGAG

p.Ser652IlefsTer51

p.S652Ifs*51

E9PAV3

protein_coding

TCGA-A2-A0D1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

NACA

insertion

Frame_Shift_Ins

rs764542193

c.896_897insC

p.Asp300ArgfsTer30

p.D300Rfs*30

E9PAV3

protein_coding

TCGA-AN-A0FY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NACA

insertion

Frame_Shift_Ins

rs764542193

c.896_897insC

p.Asp300ArgfsTer30

p.D300Rfs*30

E9PAV3

protein_coding

TCGA-BH-A1FD-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NACA

SNV

Missense_Mutation

novel

c.662N>T

p.Ala221Val

p.A221V

E9PAV3

protein_coding

deleterious_low_confidence(0.03)

benign(0.036)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NACA

SNV

Missense_Mutation

c.868N>G

p.Gln290Glu

p.Q290E

E9PAV3

protein_coding

deleterious_low_confidence(0)

benign(0.029)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

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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