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Monks et al. J Cancer Metastasis Treat 2019;5:24 I http://dx.doi.org/10.20517/2394-4722.2018.79 Page 5 of 23

PCC All Women: OR = 0.86 (0.53-1.39) and Post-menopausal: OR = 0.66 (0.29-1.50) [50]
Non-significant result (pre-diagnostic APN is not predictive of EC risk)
Pancreatic cancer - PC
PCC OR = 0.44 (0.23-0.82) - In never smoker, higher APN levels correlated to reduced risk of PC; [54]
OR = 1.59 (0.67-3.76) - No significance in smoker
OR = 0.55 (0.31, 0.98); P = 0.03 for highest vs. lowest quintile - Higher APN were negatively correlated [52]
with PC risk
Nonlinear association (P < 0.01) - Low pre-diagnostic levels of APN were associated with an elevated risk [89]
of PC
RCC P = 0.0035 - Median APN levels significantly higher in PC group than controls/chronic pancreatitis group [90]
P < 0.001 - Greater APN:Leptin ration in PC patients [91]
OR = 2.81 (1.04-7.59) - Higher APN correlated with higher odds of PC and No association with PC stage [53]
Renal cell carcinoma - RCC
RCC OR = 0.76 (0.57-1.00) P = 0.05 - Serum APN negatively correlated with RCC risk [56]
P < 0.01 (tumor size); P = 0.029 (non-metastatic vs. metastatic); P = 0.044 for total APN & P = 0.041 for [57]
HMW (non-metastatic vs. metastatic) - Strong inverse correlation was found between plasma APN levels [58]
and tumor size [57] ; Lower APN in metastatic cases [57,58]
OR = 2.3 (1.1-4.6) - Higher APN was associated with RCC risk among African American males [59]
Hepatic cancer - HC
PCC OR = 0.5 (0.22-1.15) for highest vs. lowest tertile for LMW APN - Higher % of LMW APN may be have a [92]
protective effect on HC
RCC P = 0.670; P = 0.752 - No significance difference between cases and controls [93]
Prostate cancer - PrC
PCC OR = 0.27 (0.07-0.87) for highest vs. lowest quintile for lethal PrC - Men with higher APN had reduced [94]
risk of HG or lethal Prc but overall no significant correlation between serum APN & PrC risk
NCC OR = 0.86 (0.66-1.11), P = 0.24 for all men; [60]
OR = 0.62 (0.42-0.90), P = 0.01 for obese & overweight men
APN levels negatively associated with PrC risk in obese & overweight men but not significant in all men
RCC OR = 0.29 (0.10-0.89) for highest vs. lowest quartile - Reduced risk with higher APN independent of [95]
various confounders
P < 0.05 - Significantly reduced APN in PrC patients [96]
P < 0.001 - APN levels in HG PrC were also significantly lower than LG or IG groups [97]
PCC OR = 0.87 (0.46-1.65) for highest vs. lowest tertile - No significance but the sensitivity of assays used was [98]
problematic
Lung cancer - LC
RCC P < 0.0001 - Leptin: APN ratio was significantly lower in the patients group compared to controls [99]
OR = 1.13 (0.80-4.97); OR = 0.25 (0.10-0.78) - Even though APN levels were not significantly different in [64]
cases than controls but they are significantly lower in advanced than limited disease stage
P > 0.05 [100] ; OR = 2.00 (0.80-4.97), P = 0.14 [101] - No significance [100,101]
A summary on the clinical data showing the association of serum APN with various cancers is shown. Many studies show that low
levels of APN is associated with cancer risk and its progression of disease. CRC: Colorectal cancer; PCC: prospective case-control; RCC:
Retrospective case-control; NCC: nested case control; OR: odd ratio; RR: relative risk; BC: breast cancer; EC: endometrial cancer; GC:
gastric cancer; OC: oesophageal cancer; ESCC: esophageal squamous cell cancer; EA: esophageal adenocarcinoma; PC: pancreatic
cancer; HC: liver cancer; RCC: renal cell cancer; PrC: prostate cancer; HG: high grade; LG: low grade; IG: intermediate grade

[34]
positive cells . Despite, the AdipoR1 positive group having longer survival rates, multivariate analysis
indicated this was not an independent prognostic factor on GC survival. That said, it is thought AdipoR1 is
the mediator of tumour growth suppression in GC and therefore could be a therapeutic target in tackling
GC. One study demonstrated that rs266729, an ADIPOQ variant, may be an independent prognostic factor
[35]
for non-drinking GC patients receiving surgical treatment . Similarly, APN levels have been shown to have
a direct effect in GC postoperative outcomes. It was shown that the ratio of postoperative to preoperative
[36]
levels of APN was the most useful predictor for postoperative infection . It is thought that reduced APN
[32]
levels suggest a submaximal inflammatory response, thus predisposing to infection . Increasing APN in
the weeks before surgery could be an additional method to improve surgical outcomes.

Oesophageal cancer
[32]
APN plays a significant role in the maintenance of the normal oesophageal mucosa . Lower levels of APN
have been correlated with an increased risk of oesophageal cancer (OC) [Table 1]. Low tumour expression of
[37]
AdipoR1 was suggested to be an independent predictor of improved overall OC survival . While, AdipoR2