Combined test of serum CgA and NSE improved the power of prognosis prediction of NF-pNETs

Abstract

PurposeChromogranin A (CgA) and neuron-specific enolase (NSE) are important markers for neuroendocrine tumors; however, the clinical value of combining these markers has not been well studied. In this study, we investigated the utility of each marker individually and in combination for patients with nonfunctional pancreatic neuroendocrine tumors (NF-pNETs).Patients and MethodsIn this study, NF-pNET patients and controls were recruited from December 2011 to March 2016; 784 serum samples from peripheral vein were collected. The clinical characteristics and biomarker values of all the individuals were recorded and analyzed. Tumor burdens were calculated by CT/MRI scan. Receiver-operating characteristic curves were constructed to assess the diagnostic predictive values; sensitivity and specificity were calculated to determine the cut-off value. Therapeutic responses reflected on the changes of the biomarkers’ concentration were assessed by the RECIST criterion. Clinical relations between the prognosis and the biomarker values were also analyzed. Statistical significance was defined as P value less than 0.05.ResultsAmong the 167 NF-pNETs patients, 82 were males (49.1%) and the mean age was 50.0 (17.4). The mean CgA values of G1, G2 and G3 NF-pNENs were 75, 121 and 134 μg/L (P < 0.05), respectively. In NF-pNETs, CgA correlated with the WHO tumor grade (WHO G1 vs G2, P < 0.05); the linear regression relationships were found between the tumor burdens (both in pancreas and liver) and CgA concentration (P < 0.001); changes in CgA and NSE concentrations also reflect treatment response (P < 0.001).ConclusionCgA and NSE are important diagnostic and follow-up markers in patients with NF-pNETs. The combined monitoring of CgA and NSE possesses more accuracy than individual values of CgA and NSE at predicting prognosis and disease progression.

Chromogranin A: From Laboratory to Clinical Aspects of Patients with Neuroendocrine Tumors

“…In a retrospective single-center clinical study, conducted by Yang et al, Cg A values were statistically correlated with the well-differentiated NF-pNET in the presence of hepatic metastatic disease, even if Cg A levels were not statistically significant between well-differentiated and poorly differentiated pNETs [ 70 ].…”

“…According to the study conducted by Yang et al, the therapeutic response of NF-pNETs consisted of a reduction of Cg A concentration, associated with PR and complete response in patients with this type of cancer. Contrarily, patients regarded as having progression disease or relapse had increased Cg A levels ( Figure 2 ) [ 70 ].…”

Delta‐like 3 localizes to neuroendocrine cells and plays a pivotal role in gastrointestinal neuroendocrine malignancy

“…16 Among these, CHGA is the first identified granin and is produced and excreted by granules within both endocrine glands and the diffused neuroendocrine system. [16][17][18][19] In fact, ECC cell lines used in the present study had abundant neurosecretory granules. 21 Importantly, the expression pattern of DLL3 was similar to that of CHGA in both clinical samples (Figures 2, 3 and 4) and…”

“…Our results showed that DLL3 was expressed in the cytoplasm of the cells at the deep layer of the mucosa in the GI tract (Figure A‐F). Chromogranin A ( CHGA ) is a representative marker of neuroendocrine cells . Interestingly, IHC of serial tissue sections showed that the locations of DLL3 and CHGA were similar in the specimens tested (Figure A‐E).…”

“…Chromogranin A (CHGA) is a representative marker of neuroendocrine cells. [16][17][18][19] Interestingly, IHC of serial tissue sections showed that the locations of DLL3 and CHGA were similar in the specimens tested (Figure 2A-E). To further clarify our findings, double fluorescence IHC was performed on tissue sections of normal stomach and duodenum.…”