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: SLC34A2

Gene summary for SLC34A2

Gene summary.

Gene information	Species	Human
	Gene symbol	SLC34A2
	Gene ID	10568
	Gene name	solute carrier family 34 member 2
	Gene Alias	NAPI-3B
	Cytomap	4p15.2
	Gene Type	protein-coding
	GO ID	GO:0001701
	UniProtAcc	O95436

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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
10568	SLC34A2	CA_HPV_1	Human	Cervix	CC	1.65e-18	-6.59e-01	0.0264
10568	SLC34A2	CA_HPV_2	Human	Cervix	CC	3.12e-19	-6.59e-01	0.0391
10568	SLC34A2	CA_HPV_3	Human	Cervix	CC	5.24e-12	-6.39e-01	0.0414
10568	SLC34A2	HSIL_HPV_1	Human	Cervix	HSIL_HPV	4.11e-07	-5.56e-01	0.0116
10568	SLC34A2	HSIL_HPV_2	Human	Cervix	HSIL_HPV	1.73e-06	-3.22e-01	0.0208
10568	SLC34A2	N_HPV_1	Human	Cervix	N_HPV	4.64e-05	-5.55e-01	0.0079
10568	SLC34A2	N_HPV_2	Human	Cervix	N_HPV	3.16e-09	-5.37e-01	-0.0131
10568	SLC34A2	CCI_1	Human	Cervix	CC	7.94e-05	-6.59e-01	0.528
10568	SLC34A2	CCI_3	Human	Cervix	CC	5.93e-07	-6.59e-01	0.516
10568	SLC34A2	CCII_1	Human	Cervix	CC	3.24e-10	-6.59e-01	0.3249
10568	SLC34A2	Tumor	Human	Cervix	CC	3.12e-19	-6.59e-01	0.1241
10568	SLC34A2	sample1	Human	Cervix	CC	2.68e-08	-6.59e-01	0.0959
10568	SLC34A2	sample3	Human	Cervix	CC	1.65e-18	-6.59e-01	0.1387
10568	SLC34A2	H2	Human	Cervix	HSIL_HPV	3.00e-05	-1.50e-01	0.0632
10568	SLC34A2	L1	Human	Cervix	CC	2.38e-11	-6.59e-01	0.0802
10568	SLC34A2	T1	Human	Cervix	CC	2.66e-17	-6.53e-01	0.0918
10568	SLC34A2	T3	Human	Cervix	CC	3.12e-19	-6.59e-01	0.1389
10568	SLC34A2	P1T-E	Human	Esophagus	ESCC	4.99e-02	1.04e+00	0.0875
10568	SLC34A2	P8T-E	Human	Esophagus	ESCC	4.79e-17	8.98e-01	0.0889
10568	SLC34A2	P16T-E	Human	Esophagus	ESCC	5.90e-04	1.22e-01	0.1153

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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
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
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:00017018	Cervix	CC	in utero embryonic development	71/2311	367/18723	7.21e-05	1.00e-03	71
GO:000170119	Esophagus	ESCC	in utero embryonic development	243/8552	367/18723	1.00e-15	6.86e-14	243
GO:00436275	Esophagus	ESCC	response to estrogen	45/8552	75/18723	8.75e-03	3.08e-02	45
GO:00017015	Liver	Cirrhotic	in utero embryonic development	134/4634	367/18723	2.78e-07	6.86e-06	134
GO:0043627	Liver	Cirrhotic	response to estrogen	30/4634	75/18723	2.52e-03	1.51e-02	30
GO:000170111	Liver	HCC	in utero embryonic development	204/7958	367/18723	2.44e-07	4.30e-06	204
GO:00436271	Liver	HCC	response to estrogen	44/7958	75/18723	3.44e-03	1.55e-02	44
GO:00017016	Lung	IAC	in utero embryonic development	68/2061	367/18723	1.12e-05	3.45e-04	68
GO:0006817	Lung	IAC	phosphate ion transport	8/2061	24/18723	3.09e-03	2.71e-02	8
GO:000170112	Lung	AIS	in utero embryonic development	59/1849	367/18723	1.20e-04	2.75e-03	59
GO:000170121	Lung	AAH	in utero embryonic development	24/613	367/18723	1.09e-03	3.25e-02	24
GO:000170131	Lung	MIAC	in utero embryonic development	33/967	367/18723	1.44e-03	2.54e-02	33
GO:000170125	Thyroid	HT	in utero embryonic development	39/1272	367/18723	3.72e-03	2.78e-02	39
GO:0001701111	Thyroid	PTC	in utero embryonic development	175/5968	367/18723	1.40e-10	4.73e-09	175

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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
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

SLC34A2

SNV

Missense_Mutation

novel

c.137N>T

p.Thr46Ile

p.T46I

O95436

protein_coding

tolerated(0.06)

benign(0.148)

TCGA-A2-A4S3-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SLC34A2

SNV

Missense_Mutation

novel

c.313C>A

p.Leu105Ile

p.L105I

O95436

protein_coding

tolerated(0.08)

possibly_damaging(0.46)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SLC34A2

SNV

Missense_Mutation

c.203N>G

p.Asp68Gly

p.D68G

O95436

protein_coding

deleterious(0)

probably_damaging(0.948)

TCGA-B6-A0WX-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

SLC34A2

SNV

Missense_Mutation

c.1284N>A

p.Phe428Leu

p.F428L

O95436

protein_coding

tolerated(0.06)

benign(0.344)

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SLC34A2

SNV

Missense_Mutation

rs115874588

c.1538N>A

p.Arg513His

p.R513H

O95436

protein_coding

tolerated(0.19)

benign(0.077)

TCGA-BH-A18P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SLC34A2

SNV

Missense_Mutation

rs148403466

c.700N>A

p.Val234Met

p.V234M

O95436

protein_coding

deleterious(0.02)

benign(0.117)

TCGA-LD-A9QF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxol

SLC34A2

SNV

Missense_Mutation

rs76854178

c.1342G>A

p.Val448Met

p.V448M

O95436

protein_coding

deleterious(0.02)

possibly_damaging(0.74)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SLC34A2

SNV

Missense_Mutation

c.1611N>A

p.Phe537Leu

p.F537L

O95436

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-C5-A3HE-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SLC34A2

SNV

Missense_Mutation

rs775481758

c.1658G>A

p.Arg553Gln

p.R553Q

O95436

protein_coding

tolerated(0.84)

benign(0)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SLC34A2

SNV

Missense_Mutation

rs78448446

c.334N>A

p.Val112Met

p.V112M

O95436

protein_coding

deleterious(0)

probably_damaging(0.981)

TCGA-JX-A3PZ-01

Cervix

cervical & endocervical cancer

Female

<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
10568	SLC34A2	CLINICALLY ACTIONABLE, TRANSPORTER, DRUGGABLE GENOME	antibody	252166615

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