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: NISCH

Gene summary for NISCH

Gene summary.

Gene information	Species	Human
	Gene symbol	NISCH
	Gene ID	11188
	Gene name	nischarin
	Gene Alias	I-1
	Cytomap	3p21.1
	Gene Type	protein-coding
	GO ID	GO:0003008
	UniProtAcc	Q9Y2I1

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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
11188	NISCH	Dong_P1	Human	Prostate	Tumor	8.77e-08	5.14e-02	0.035
11188	NISCH	Dong_P3	Human	Prostate	Tumor	9.49e-19	2.81e-01	0.0278
11188	NISCH	Dong_P4	Human	Prostate	Tumor	1.98e-02	1.50e-01	0.0292
11188	NISCH	Dong_P5	Human	Prostate	Tumor	1.28e-12	7.41e-03	0.053
11188	NISCH	GSM5353215_PA_AUG_PB_1B_S2	Human	Prostate	Tumor	2.36e-03	6.31e-01	0.1557
11188	NISCH	GSM5353221_PA_PB2A_Pool_1_3_S25_L001	Human	Prostate	Tumor	1.63e-05	4.35e-01	0.1633
11188	NISCH	GSM5353222_PA_PB2B_Pool_1_3_S52_L002	Human	Prostate	Tumor	9.23e-05	3.82e-01	0.1608
11188	NISCH	GSM5353223_PA_PB2B_Pool_2_S26_L001	Human	Prostate	Tumor	4.86e-08	5.44e-01	0.1604
11188	NISCH	GSM5353236_PA_PR5251_T1_S7_L001	Human	Prostate	Tumor	3.81e-05	6.09e-01	0.1608
11188	NISCH	GSM5353237_PA_PR5251_T2_S8_L001	Human	Prostate	Tumor	3.67e-02	4.88e-01	0.1622
11188	NISCH	GSM5353240_PA_PR5254_T1_S15_L001	Human	Prostate	Tumor	7.35e-05	3.82e-01	0.1575
11188	NISCH	GSM5353243_PA_PR5261_T1_S23_L002	Human	Prostate	Tumor	3.09e-02	2.81e-01	0.1545
11188	NISCH	GSM5353244_PA_PR5261_T2_S24_L002	Human	Prostate	Tumor	9.31e-03	2.65e-01	0.1569
11188	NISCH	male-WTA	Human	Thyroid	PTC	8.24e-24	1.90e-01	0.1037
11188	NISCH	PTC01	Human	Thyroid	PTC	1.13e-07	1.43e-01	0.1899
11188	NISCH	PTC03	Human	Thyroid	PTC	6.00e-05	2.40e-01	0.1784
11188	NISCH	PTC04	Human	Thyroid	PTC	1.58e-11	2.88e-01	0.1927
11188	NISCH	PTC05	Human	Thyroid	PTC	2.16e-10	4.67e-01	0.2065
11188	NISCH	PTC06	Human	Thyroid	PTC	3.10e-25	4.97e-01	0.2057
11188	NISCH	PTC07	Human	Thyroid	PTC	9.66e-23	3.24e-01	0.2044

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		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
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:000599621	Liver	HCC	monosaccharide metabolic process	167/7958	257/18723	2.31e-13	1.25e-11	167
GO:001931821	Liver	HCC	hexose metabolic process	155/7958	237/18723	7.63e-13	3.90e-11	155
GO:000600621	Liver	HCC	glucose metabolic process	128/7958	196/18723	8.60e-11	3.06e-09	128
GO:000726521	Liver	HCC	Ras protein signal transduction	187/7958	337/18723	8.89e-07	1.35e-05	187
GO:001660121	Liver	HCC	Rac protein signal transduction	28/7958	42/18723	1.35e-03	7.26e-03	28
GO:00072659	Oral cavity	OSCC	Ras protein signal transduction	185/7305	337/18723	1.95e-09	4.60e-08	185
GO:00059968	Oral cavity	OSCC	monosaccharide metabolic process	129/7305	257/18723	1.63e-04	1.13e-03	129
GO:00166018	Oral cavity	OSCC	Rac protein signal transduction	28/7305	42/18723	2.61e-04	1.67e-03	28
GO:00193188	Oral cavity	OSCC	hexose metabolic process	118/7305	237/18723	4.53e-04	2.73e-03	118
GO:00060068	Oral cavity	OSCC	glucose metabolic process	98/7305	196/18723	1.10e-03	5.63e-03	98
GO:000726514	Prostate	Tumor	Ras protein signal transduction	101/3246	337/18723	6.29e-09	2.44e-07	101
GO:005127114	Prostate	Tumor	negative regulation of cellular component movement	92/3246	367/18723	1.03e-04	9.99e-04	92
GO:000600613	Prostate	Tumor	glucose metabolic process	55/3246	196/18723	1.22e-04	1.14e-03	55
GO:200014614	Prostate	Tumor	negative regulation of cell motility	89/3246	359/18723	1.99e-04	1.74e-03	89
GO:001660112	Prostate	Tumor	Rac protein signal transduction	17/3246	42/18723	3.45e-04	2.73e-03	17
GO:004001313	Prostate	Tumor	negative regulation of locomotion	94/3246	391/18723	4.20e-04	3.21e-03	94
GO:003033613	Prostate	Tumor	negative regulation of cell migration	84/3246	344/18723	4.95e-04	3.66e-03	84
GO:00193187	Prostate	Tumor	hexose metabolic process	59/3246	237/18723	1.96e-03	1.14e-02	59
GO:00059967	Prostate	Tumor	monosaccharide metabolic process	62/3246	257/18723	3.38e-03	1.75e-02	62
GO:000726519	Thyroid	PTC	Ras protein signal transduction	162/5968	337/18723	3.16e-10	1.02e-08	162

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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

NISCH

SNV

Missense_Mutation

c.544N>A

p.Asp182Asn

p.D182N

Q9Y2I1

protein_coding

deleterious(0)

probably_damaging(0.975)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NISCH

SNV

Missense_Mutation

rs773401264

c.2936N>A

p.Arg979His

p.R979H

Q9Y2I1

protein_coding

tolerated(0.08)

probably_damaging(0.932)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

NISCH

SNV

Missense_Mutation

c.3322N>C

p.Ser1108Arg

p.S1108R

Q9Y2I1

protein_coding

deleterious(0)

possibly_damaging(0.638)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

NISCH

SNV

Missense_Mutation

novel

c.2480G>T

p.Ser827Ile

p.S827I

Q9Y2I1

protein_coding

tolerated(0.06)

possibly_damaging(0.731)

TCGA-BH-A1FC-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NISCH

insertion

In_Frame_Ins

novel

c.476_477insGGG

p.Glu159_Gln160insGly

p.E159_Q160insG

Q9Y2I1

protein_coding

TCGA-A2-A0EM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

NISCH

insertion

Frame_Shift_Ins

novel

c.1762_1763insGATATAAATCCTTGTCAAA

p.Leu588ArgfsTer53

p.L588Rfs*53

Q9Y2I1

protein_coding

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

NISCH

deletion

Frame_Shift_Del

novel

c.3770delN

p.Cys1257SerfsTer2

p.C1257Sfs*2

Q9Y2I1

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

NISCH

SNV

Missense_Mutation

novel

c.3997G>A

p.Ala1333Thr

p.A1333T

Q9Y2I1

protein_coding

deleterious(0)

possibly_damaging(0.79)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NISCH

SNV

Missense_Mutation

novel

c.1896N>T

p.Gln632His

p.Q632H

Q9Y2I1

protein_coding

tolerated(0.13)

benign(0)

TCGA-C5-A1M6-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NISCH

SNV

Missense_Mutation

c.3460N>C

p.Glu1154Gln

p.E1154Q

Q9Y2I1

protein_coding

deleterious(0.04)

probably_damaging(0.991)

TCGA-EK-A2R8-01

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

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