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Role of Syn Expression in Non-Small Cell Lung Cancer




Introduction:


Synaptophysin (Syn) is positively expressed in almost all neuroblastomas and is commonly used for the identification and diagnosis of neuroendocrine tumors. However, continuous research indicates that the expression of Syn in non-small cell lung cancer (NSCLC) is associated with TNM staging, lymph node metastasis, and prognosis, holding certain clinical value in the diagnosis and prognostic assessment of NSCLC.


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Syn is an acidic glycoprotein with a molecular weight of 38 kDa, first extracted from rat brain synaptic vesicles by Jahn in 1885, also known as p38. The protein molecule has four transmembrane domains and cytoplasmic N- and C-termini, primarily located in the presynaptic vesicle membrane of neurons, involved in cellular vesicle transport and calcium balance regulation.
Syn is widely expressed in neuroendocrine tumors, including neuroblastoma, ganglioneuroblastoma, pheochromocytoma, and non-pheochromocytoma paraganglioma, and is also expressed in epithelial neuroendocrine tumors. It is recognized as a marker for neuroendocrine tumors.
Other studies have shown that the expression of Syn in NSCLC is associated with TNM staging, lymph node metastasis, and prognosis, holding certain clinical value in the diagnosis and prognostic assessment of NSCLC.
In early research, Dai Yun et al. performed immunohistochemical detection of Syn expression in specimens from 123 NSCLC patients and found that the positive expression rate of Syn was adenosquamous carcinoma > squamous cell carcinoma > adenocarcinoma. There were significant differences in expression among tumor tissue specimens with varying degrees of differentiation (P<0.05). Moreover, NSCLC patients with positive Syn expression had shorter survival periods, suggesting that positive Syn expression is an independent risk factor affecting patient prognosis.
Zhang Jun et al. conducted Syn immunohistochemical staining studies and a three-year follow-up on specimens from 206 NSCLC patients in stages I–IIIa. The results showed that Syn mostly exhibited diffuse cytoplasmic staining, with a positive rate of up to 44.2% (91 cases). The positive expression of Syn in patients with lymph node metastasis was significantly higher than in those without lymph node metastasis (P=0.028). Additionally, as the positive rate of Syn increased, the degree of tumor differentiation showed a decreasing trend (P<0.05). Meanwhile, all follow-up results indicated that the higher the Syn positive rate, the shorter the postoperative survival period of patients (χ²=4.164, P=0.041), suggesting that Syn can serve as an indicator for lymph node metastasis and prognosis in NSCLC.
Jianguo Feng et al. used tissue microarray technology to perform immunohistochemical examinations on 451 NSCLC patients, analyzing the relationship between Syn expression and the pathological and clinical characteristics of NSCLC. Positive immunostaining was observed in 86 cases (19.1%) in the tissue microarray (as shown in Figure 1). Further studies revealed that positive Syn expression was significantly correlated with TNM staging in NSCLC (P<0.05): the percentage of Syn expression was higher in advanced-stage tumors, but there was no association with other pathological factors such as gender, age, and family history (P>0.05). In Kaplan-Meier analysis and Log-rank tests, it was found that Syn expression was significantly related to patients’ overall survival (OS) and disease-free survival (DFS): patients with high Syn expression had significantly lower OS and DFS than those with low Syn expression (as shown in Figure 2), indicating that Syn expression can serve as an indicator for clinical TNM staging and prognosis in NSCLC.

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Figure 1. Representative images of positive and negative Syn expression in NSCLC

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Figure 2. Relationship between Syn expression and prognosis in NSCLC


Furthermore, the latest related research by Robert K. Nam and Xi Jianmin et al. suggests that one reason for the association between Syn expression in NSCLC tissues and prognosis, staging, and metastasis is that Syn inhibits the epithelial-mesenchymal transition of tumor cells. During this transition, changes in the extracellular matrix components of tumor cells can degrade adhesive proteoglycans and collagen, leading to decreased adhesion and subsequent tumor metastasis.
Therefore, positive expression of Syn in NSCLC tissues can serve as one of the related indicators for TNM staging, lymph node metastasis, and prognosis.



Related Antibodies from Maixin



Antibody Name

Product Number

Clone Number

Positive Location

Syn*

MAB-0742

MX038

Cytoplasm

Syn
Kit-0022
SP11
Cytoplasm

References:

[1] Dai Yun, Han Baohui, Shen Jie, He Weizhong, Shao Jingchen. Expression of CgA and SYN in Non-Small Cell Lung Cancer and Their Relationship with Prognosis [J]. Journal of Shanghai Jiaotong University (Medical Science), 2008(09):1100-1103+1114.

[2] Jun ZHANG,Kai ZHENG,Yan GUO, Peng ZHANG, Zhongli ZHAN. Research on the Relationship between Non-small Cell Lung Cancer with Neuroendocrine Differentiation and the Biological Characteristics and Prognosis[J]. Chinese Journal of Lung Cancer,2010,13(9):873-876

[3] Feng Jianguo,Sheng Huaying,Zhu Chihong,Qian Xiaoqian,Wan Danying,Su Dan,Chen Xufeng,Zhu Liming. Correlation of neuroendocrine features with prognosis of non-small cell lung cancer.[J]. Oncotarget,2016,7(4-4):71727-71736

[4] Nam Robert K,Benatar Tania,Amemiya Yutaka,Wallis Christopher J D,Romero Joan Miguel,Tsagaris Melina,Sherman Christopher,Sugar Linda,Seth Arun. MicroRNA-652 induces NED in LNCaP and EMT in PC3 prostate cancer cells.[J]. Oncotarget,2018,9(27):19159-19176

[5] Xi Jianmin, Tan Xiaoning, Wen Huan, Lu Weiqian, Huang Jin. Study on the Relationship Between PD-L1, TTF-1, SYN Expression in Non-Small Cell Lung Cancer Tissues and Clinicopathological Features and Prognosis [J]. Progress in Modern Biomedicine, 2021, 21(13):2517-2521.

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