Table 1.

Expression and function of NUCB2/NESF-1 in different cancer types.

Cancer Type	Evaluation Method	NUCB2/NESF-1 Expression/Function	Ref.
Breast cancer	IHC	NUCB2/NESF-1 was positively associated with the ER status of breast carcinoma patients, lymph node metastasis, clinical stage, and an increased risk of recurrence; NUCB2/NESF-1 was an independent prognostic factor for disease-free survival.	[41,42]
	In vitro	Inhibition of NUCB2/NESF-1 expression in MCF-7 and SKBR-3 resulted in decreased proliferation, invasion, and migration properties; NUCB2 expression was upregulated by estradiol in ER-positive MCF-7 cells.
Colon cancer	IF	The expression of NUCB2/NESF-1 in cancer was higher than in non-tumor regions; NUCB2/NESF-1 was predominantly expressed in the cytoplasm and much less in the cancer cell membrane. The results also indicated a positive correlation between NUCB2/NESF-1 expression and lymph node metastasis and the TNM stage.	[45]
	ELISA	There was no difference in serum nesfatin-1 concentration between healthy donors and colon cancer patients.
	In vitro	NUCB2/NESF-1 enhanced EMT, migration, and invasion in colon cancer cells.
Bladder cancer	IHC	High expression of NUCB2/NESF-1 was associated with distant metastasis and vascular invasion. Patients with high NUCB2/NESF-1 had poor overall survival and progression-free survival rates	[46]
	In vitro	Suppression of NUCB2/NESF-1 using shRNA in T24 and 5637 bladder cancer cell lines resulted in the inhibition of cell proliferation, migration, and invasion abilities compared to the control. NUCB2/NESF-1 knockdowned cells had a lower expression of MMP2 and MMP9.
	In vivo	The growth of tumors from NUCB2/NESF-1knockdowned cells in BALB/c mice was slower compared to the control, and lung metastases were observed only in the control group.
Ovarian cancer	In vitro
		Administration of recombinant human nesfatin-1 resulted in enhanced apoptosis and decreased ovarian cancer cell proliferation.	[70]
Prostate cancer	real time RT—PCR, IHC	Expression of NUCB2/NESF-1 was significantly higher in cancer cells than noncancerous control and correlated with higher Gleason scores, higher levels of preoperative PSA, positive lymph node metastasis and positive angiolymphatic invasion. High NUCB2/NESF-1 mRNA level was an independent predictor of shorter BCR-free survival. Multivariate Cox analysis indicated that NUCB2/NESF-1 mRNA was an independent prognostic factor for the overall survival of prostate cancer patients.	[47,48,49]
Gastric cancer	IHC	NUCB2 was localized in the nuclei, and its expression was higher in the tumor than in the adjacent normal tissues. NUCB2 was significantly associated with tumor depth, lymph node metastasis, lymphatic invasion, venous invasion, and clinical stage. NUC2/NESF-1 was an independent predictor of progression-free survival. A positive correlation was found between the expression of NUCB2/NESF-1 and EMT-related genes such as DSP, ITGAV, MMP3, TSPAN13, and CDH2.	[52]
Papillary thyroid cancer	IHC	Papillary thyroid cancer showed nucleus and cytoplasmic expression with no staining in the normal tissue adjacent to cancer. NUCB2/NESF-1 was significantly associated with extrathyroidal extension, TNM stage, and tumor size.	[53]
	In vitro	Inhibition of NUCB2/NESF-1 expression in TPC-I and KI thyroid cell lines resulted in decreased proliferation, invasion, and migration properties and decreased expression of invasion-related proteins (MMP-2 and MMP).
Renal cell carcinoma	IHC	The expression of NUCB2/NESF-1 was significantly higher in the tumor compared to the control. NUCB2/NESF-1 expression was associated with the T stage and the presence of metastasis. High NUCB2/NESF-1 expression was associated with a shorter overall survival rate. NUCB2/NESF-1 was an independent prognostic factor for overall survival. NUCB2 was positively correlated with the Fuhrman grade (p < 0.002) and the presence of necrosis.	[55,56,57]
	In vitro	Inhibition of NUCB2/NESF-1 expression in the 786-O renal cancer cell line resulted in an increased apoptosis rate and a decreased invasion rate. NUCB2/NESF-1 knockout in the SK-RC-52 cell line inhibited migration, invasion, and affected EMT-related proteins
Adreno- cortical cancer	In vitro	Treatment of H295R cells with nesfatin-1resulted in a decreased proliferative capacity. Nesfatin-1 induced a concentration-dependent increase in apoptosis of H295R cells compared to control cells	[69]
Glioblastoma	Real-time RT- PCR, IHC	mRNA expression level of NUCB2/NESF-1 in glioblastoma was significantly higher than in normal tissues. NUCB2/NESF-1 was predominantly expressed in the nucleus and was highly overexpressed in glioblastoma compared to the adjacent tissue. High expression of NUCB2/NESF-1 was related to recurrence.	[58]
	In vitro	Inhibition of NUCB2/NESF-1 expression in U251 and U87 glioblastoma cell lines resulted in decreased proliferation, invasion, and migration properties
	In vivo	The tumor volume of the NUCB2/NESF-1 ablation group was significantly smaller than the control; the occurrence of lung metastasis was decreased in mice injected with NUCB2/NESF-1 knockdowned U251 cells compared to the control.
Endometrial cancer	IHC	NUCB2/NESF-1 was positively correlated with the Ki-67 marker of proliferation. No association was found between NUCB2/NESF-1 expression and other clinicopathological parameters. NUCB2/NESF-1 status was significantly associated with an increased risk of recurrence (p = 0.004). NUCB2/NESF-1 status was an independent prognostic factor for disease-free survival and cancer-specific survival.	[50]
	In vitro	Knockdown of NUCB2/NESF-1 using a specific siRNA significantly inhibited Ishikawa and Sawano endometrial cancer cell proliferation and migration. Treatment of Ishikawa cells with recombinant nesfatin-1 also promoted cell proliferation and migration.