Table 1.

NUAK1 and NUAK2 expression correlates with clinical parameters of cancer

Cancer type	Clinicopathologic features	Reference
Glioblastoma	•NUAK1 protein is more highly expressed in tumor than in surrounding normal brain tissue from the same patient •NUAK1 IHC expression (−) correlates with patient survival and clinicopathologic grade; NUAK2 mRNA (+) correlates with glioma grade according to the TCGA database •NUAK2 mRNA (−) correlates with percent probability of survival	(31, 32)
Nasopharyngeal carcinoma	•NUAK1 expression is higher in NPC tumors than in normal nasopharynx per analysis of Oncomine database •NUAK1 IHC expression (+) correlates with lymph node size and high-risk histopathological subtype •NUAK1 expression predicts lower OS and DFS	(33)
Esophageal squamous cell carcinoma	•NUAK1 mRNA is elevated in ESCC compared to normal esophagus and EAC •High NUAK1 expression (−) correlates with OS in ESCC patients •NUAK1 IHC score is higher in ESCC compared to normal esophagus and (+) correlates with lymph node metastasis, tumor invasion depth, advanced pathological TNM stage, and poor survival	(35)
Breast cancer	•NUAK1 RNA is upregulated in 30 patient samples •NUAK1 IHC staining intensity on patient tumor samples (+) correlates with clinical stage and lymph node metastasis and (−) correlates with survival •NUAK2 RNA and protein are upregulated in 30 patient samples compared to adjacent normal breast •NUAK2 RNA expression (+) correlated with stage and lymph node metastasis; patient samples with high NUAK2 IHC expression had lower OS than patient samples with low expression •NUAK1 and NUAK2 mRNA expression is higher in tumor than normal breast, (+) correlates with stage and grade, and is highly expressed in metastasis compared to primary tumor by GSE15852, GSE42568, GSE54002, and TCGA datasets	(42, 43, 44)
NSCLC	•NUAK1 IHC expression is higher in tumor samples than in normal lung, (+) correlates with lymph node metastasis and (−) correlates with OS •NUAK1 and NUAK2 mRNA are higher in NSCLC metastases than in primary site; NUAK1 and NUAK2 RNA expression (−) correlates with survival and (+) correlates with stage	(37, 38, 40)
Hepatocellular carcinoma	•NUAK1 is more highly expressed in human HCC patient samples by IHC, PCR, and western blot than in matched non tumor tissues of the same patients, and NUAK1 expression by IHC (−) correlates with survival in HCC •NUAK2 is more highly expressed in 233 HCC tumor samples compared to paired normal liver tissue	(50, 51, 52)
Gastric cancer	•NUAK1 IHC expression is higher in GC compared to adjacent normal tissue, (+) correlates with depth of invasion, stage, grade, metastasis and (−) with OS, and RFS •NUAK2 protein is upregulated in human GC samples compared to adjacent normal controls	(55, 56)
Colorectal carcinoma	•NUAK1 expression in TCGA and meta-analysis cohorts (+) correlates with stage and (−) correlates with OS •ISH of NUAK1 on TMA of CRC samples show NUAK1 (+) correlates with CRC stage	(59)
Pancreatic cancer	•NUAK1 protein is elevated in PAAD samples compared to paired normal tissue (61); NUAK1 RNA expression is higher in PDAC than normal pancreas and patients with NUAK1 high PDAC tumors exhibit shorter survival than NUAK1 low tumors •p-NUAK1 is elevated by IHC in a TMA of 100 PDAC samples •NUAK2 is more highly expressed by IHC in PDAC compared to adjacent normal pancreatic tissue	(61, 62, 64)
Renal cell carcinoma	•NUAK1 expression elevated in RCC and (+) correlates with grade, stage, mitotic index, and poor response to chemotherapy	(66)
Cervical cancer	•NUAK1 RNA expression is elevated in cancerous compared to normal tissue from the same patients •NUAK1 expression negatively correlates with overall survival of CESC patients •NUAK2 is more highly expressed in CC tumors than in normal cervical tissue according to UALCAN database and in CC cell lines than in normal primary cervix cells •NUAK2 protein is more highly expressed in CC patient tumors than in normal cervix	(67, 68)
Ovarian cancer	•NUAK1 RNA expression (−) correlates with PFS by analysis of several Affymetrix microarray datasets •NUAK1 transcript level is lower in less differentiated subtypes of ovarian cancer and (+) associated with risk of disease diagnosis at an older age and with risk of residual disease post tumor debulking surgery	(69)
Bladder cancer	•NUAK2 IHC expression is higher in high grade primary bladder cancer samples than in low grade •NUAK2 expression (+) correlates with disease recurrence in cohort of muscle invasive bladder cancer	(20)
Prostate cancer	•NUAK1 mRNA is more highly expressed in PC samples than in normal prostate tissue and expression (−) correlates with survival •NUAK2 is more highly expressed in PC patient samples and mCRPC than in normal matched tissue and the upper 50 percentile of NUAK2 expression (+) correlates with a higher likelihood of metastasis	(74, 75)
Acral melanoma	•High NUAK2 expression (−) correlates with RFS in acral melanoma via Kaplan–Meier curve; NUAK2 expression by IHC on acral melanoma clinical samples correlates with stage, RFS, and OS.	(77, 79)

Listed are 15 cancer types where either NUAK1, NUAK2, or both NUAK1 and NUAK2 are differentially expressed in normal compared to cancerous tissue or correlate with clinicopathologic features of disease.

(+), positively; (−), negatively; CESC, cervical squamous cell carcinoma and endocervical adenocarcinoma; CRC, colorectal cancer; DFS, disease free survival; EAC, esophageal adenocarcinoma; ISH, in situ hybridization; IHC, immunohistochemistry; mCRPC, metastatic castrate-resistant prostate cancer; NSCLC, non–small cell lung cancer; NUAK, novel (nua) kinase; OS, overall survival; PDAC, pancreatic ductal adenocarcinoma; PFS, progression free survival; RFS, recurrence-free survival; TCGA, the cancer genome atlas program; TMA, tissue microarray; TNM, tumor, node, and metastasis; UALCAN, University of Alabama at Birmingham Cancer data analysis portal.