Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 4  |  Page : 856-859

Expression of fascin_1 protein in cancer tissues of patients with nonsmall cell lung cancer and its relevance to patients' clinicopathologic features and prognosis


Department of Respiratory, The 3rdPeoples' Hospital of Hangzhou City, Hangzhou Shi, Zhejiang, China

Date of Web Publication27-Jun-2018

Correspondence Address:
Yunxia Zhang
Department of Respiratory, The 3rd Peoples' Hospital of Hangzhou City, Hangzhou Shi, Zhejiang
China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_732_17

Rights and Permissions
 > Abstract 


Objective: The aim of this study is to explore the expression of Fascin_1 protein in cancer tissues of patients with nonsmall cell lung cancer (NSCLC) and its relevance to patients' clinicopathologic features and prognosis.
Methods: Retrospective analysis was performed on 81 patients with NSCLC who were admitted to our hospital and received surgical treatment from February 2012 to March 2016. To analyze the correlation of Fascin_1 protein expression in cancer tissues with the clinicopathologic features and prognosis of the patients, the immuno-histochemical method was applied to examine Fascin_1 protein expression in cancer and normal paracarcinoma tissues of the included 81 NSCLC patients.
Results: Fascin_1 protein was diffused in cancer tissues, and cancer cells surrounding the carcinoma lesions were strongly stained. The protein was mainly located on the cytoplast or membrane of positive cells and manifested as a focal or diffuse brown granular distribution. The negative, weakly positive, and strongly positive expression rates in cancer tissues were 23.5% (19/81), 35.8% (29/81), and 40.7% (33/81), respectively. The negative, weakly positive, and strongly positive expression rates in paracarcinoma tissues were 71.6% (58/81), 12.3% (10/81), and 16% (13/81), respectively. The difference was statistically significant (P < 0.05), and the positive expression rate of Fascin_1 in cancer tissues was significantly higher than that of in paracarcinoma tissues (P < 0.05). The positive expression of Fascin_1 in cancer tissues was significantly correlated with the neoplasm stage (P < 0.05) and mediastinal lymph node metastases (P < 0.05); however, it was not relevant to the patients' age, gender, tumor size, pathological type, tumor grading, or pleural effusion (P > 0.05). The median survival times for patients with positive Fascin_1 and negative Fascin_1 expression in cancer tissues were 26 and 44 months, respectively, indicating that the median survival time of the Fascin_1-positive group was significantly lower than that of in the Fascin_1-negative group (heart rate = 2.74, 95% confidence interval: 1.32–6.87, P < 0.05).
Conclusions: Fascin_1 protein expression in NSCLC tissues and normal paracarcinoma issues were different. Fascin_1 expression in cancer tissues was related to the poor prognosis of NSCLC patients.

Keywords: Cancer tissue, clinical features, expression, fascin_1 protein, nonsmall cell lung cancer


How to cite this article:
Zhang Y, Liang B, Dong H. Expression of fascin_1 protein in cancer tissues of patients with nonsmall cell lung cancer and its relevance to patients' clinicopathologic features and prognosis. J Can Res Ther 2018;14:856-9

How to cite this URL:
Zhang Y, Liang B, Dong H. Expression of fascin_1 protein in cancer tissues of patients with nonsmall cell lung cancer and its relevance to patients' clinicopathologic features and prognosis. J Can Res Ther [serial online] 2018 [cited 2019 Nov 14];14:856-9. Available from: http://www.cancerjournal.net/text.asp?2018/14/4/856/235095




 > Introduction Top


Clinically, lung cancer is one of the most common solid malignant tumors. Epidemiological study [1] showed that the incidence of malignant tumor was the highest in lung cancer among males in China. However, the molecular mechanism occurrence, development, invasion, and metastasis of lung cancer remained unclear. Therefore, studies on such mechanisms may provide new insights with and targets for the further treatment of lung cancer.[2],[3] With the constant development of molecular biological techniques, numerous oncogenes and cancer suppressor genes have been found. An increasing number of signaling pathways have been discovered for the regulation of lung cancer occurrence and metastasis, bringing about hope for the treatment of lung cancer.

The Fascin_1 gene of humans was first cloned in 1994. Its chromosome was located in 7q22, and its protein-coding product was intracellular protein, which could bond with F-actin. The 39th serine of Fascin_1 protein was the phosphorylation site of proteinkinase C.[4] The phosphorylation site can play many roles, including regulating the binding activity of Fascin_1 protein and F-actin, inhibiting the assembly of Fascin_1 troponin, and affecting the formation of pseudopodia and microspikes on the cell membrane surface. Recently, the high expression level of Fascin_1 protein was reported in multiple solid tumor tissues, which had a certain relationship with clinicopathologic features of patients.[5],[6],[7] This study was aimed to test the expression of Fascin_1 protein in cancer and paracarcinoma tissues of 81 patients with nonsmall cell lung cancer (NSCLC) and explore its relevance to the clinicopathologic features and prognosis.


 > Methods Top


Patients

A retrospective analysis was conducted on 81 patients with NSCLC who were admitted to our hospital and received surgical treatment from February 2012 to March 2016. The inclusion criteria were as follows: (1) patients were confirmed to be NSCLC through postoperative pathological examination; (2) patients did not suffer from severe postoperative complications; and (3) patients with complete clinicopathologic data. The exclusion criteria were as follows: (1) patients received palliative surgery; (2) patients also suffered from other tumors; (3) patients died during the perioperative period; and (4) patients suffered from metastatic tumor of the lungs. The age of selected 81 patients were 68.6 ± 13.4 years. Among them, there were 50 cases of male and 31 cases of female. The tissue specimens of the patients were obtained on their consent and signature on the informed consent form.

Reagents and instruments

Mouse anti-human Fascin_1 monoclonal antibody (SPM133) for immuno-histochemistry was purchased (Santa Cruz, USA). The immuno-histochemical test kit (MaxVision kit) and DAB substrate kit were purchased from MXB Biotechnologies Co.

Immunohistochemistry assay

The immuno-histochemical staining method was performed according to the manufacturer's instructions. MaxVision two-step method was applied for immuno-histochemical staining. Sodium citrate buffer solution was applied for antigen retrieval under high pressure. The slice was added drop-wise with Fascin_1 primary antibody and left overnight at 4°C. The primary antibody was removed and a second antibody was added, and the slice was incubated at room temperature for 20 min. DAB was applied for color development, and hematoxylin was involved for counterstaining. The expression of Fascin_1 in vascular endothelial cells was used as the positive control, whereas PBS was applied for the substitute ofprimary antibody as the negative control.

Fascin_1 protein expression criterion

Fascin_1 protein was mainly located on the cytoplast or membrane of positive cells. The scoring standard for staining intensity was as follows: colorless = 0, canary brown = 1, light brown = 2, and brown = 3. The scoring standard for staining degree was as follows: if no positive cell was observed, the score was 0; if positive cells accounted for 1%–25%, the score was 1; in case of 26%–50%, the score was 2; in case of 51%–75%, the score was 3; and in case of 76%–100%, the score was 4. The final score was the sum of staining intensity score and staining degree score. If the sum of two items (ranged 0–7 scores) was equal to or higher than 3, it was considered to be positive.[8]


 > Results Top


Fascin_1 protein positive expression

Fascin_1 protein was diffused in cancer tissues, and cancer cells surrounding the carcinoma lesions were strongly stained. The protein was mainly located on the cytoplast or membrane of positive cells and manifested as a focal or diffuse brown granular distribution [Figure 1]. The negative, weakly positive, and strongly positive expression rates in cancer tissues were 23.5% (19/81), 35.8% (29/81), and 40.7% (33/81), respectively. The negative, weakly positive, and strongly positive expression rates in paracarcinoma tissues were 71.6% (58/81), 12.3% (10/81), and 16% (13/81), respectively. The difference was statistically significant (P< 0.05), and the positive expression rate of Fascin_1 in cancer tissues was significantly higher than that of in paracarcinoma tissues (P< 0.05), [Table 1].
Figure 1: Fascin_1 positive expression in nonsmall cell lung cancer tissue ([a]: weak positive, ×20; [b]: weak positive ×40; [c]: strong positive, ×20; [d]: strong positive, ×40)

Click here to view
Table 1: The positive of Fascin_1 protein in cancer and para-cancer tissues

Click here to view


Fascin_1 expression and clinical features

The positive expression of Fascin_1 in cancer tissues was significantly correlated with the patients' clinical stage (P< 0.05) and mediastinal lymph node metastases (P< 0.05); however, it was not relevant to the patients' age, gender, tumor size, pathological pattern, tumor grading, or pleural effusion (P > 0.05) [Table 2].
Table 2: Correlation between Fascin_1 expression and patient's clinical features

Click here to view


Fascin_1 expression and prognosis

The median survival time of the patients with positive Fascin_1and negative Fascin_1expression in cancer tissues were 26 and 44 months, respectively, indicating that the median survival time of the Fascin_1-positive group was significantly lower than that of in the Fascin_1-negative group (heart rate = 2.74, 95% confidence interval: 1.32–6.87, P < 0.05).


 > Discussion Top


Fascin_1 protein belonged to the cytoskeletal protein family, which bound with F-action and was located on cell membrane protuberances and other sites.[9] The formation of cell membrane protuberances would be regulated and affected by the Fascin_1 protein.[10],[11] It also participated in the rearrangement, cell movement, and migration of actin cytoskeleton.[12] Thus, Fascin_1 protein was probably related to the invasion and metastasis of cancer cells. Numerous studies [13],[14] have been performed on the relevance between Fascin_1 protein expression and tumor patients' prognosis, but there was few studies focused on the relevance between Fascin_1 expression in tumor tissues of Chinese NSCLC patients and the clinicopathologic features, such asage, gender, neoplasm stage, pathological grade, and tumor size. Therefore, in this study, the immuno-histochemical assay was applied to investigate the expression of Fascin_1 protein in the tissue specimens, which were sampled from the patients who were hospitalized and received surgical treatment in our hospital in recent years.

This study focused on the relevance of Fascin_1 protein expression in tumor tissues to patients' clinicopathologic features and prognosis. In our result, the Fascin_1 protein expression incancerous tissues of the NSCLS patients was significantly higher than that of in paracarcinoma tissues, indicating a potential correlation ofFascin_1with the occurrence and development of NSCLC. Further analysis showed that the positive expression of Fascin_1 in cancerous tissues was significantly associated with the patients' neoplasm stage (P< 0.05) and mediastinal lymph node metastases (P< 0.05), while it was unrelated to other clinicopathologic features (P > 0.05). Survival analysis suggested that the median survival time of the patients with positive Fascin_1 expression in cancerous tissues was considerably shorter than that of in the patients with negative Fascin_1 expression. This result indicated that the positive expression of Fascin_1 in tumor tissues of the patients with NSCLC was probably correlated with their poor prognosis. In addition, the expression of Fascin_1 protein in NSCLC tissues greatly differed from that of in normal paracarcinoma tissues. Thus, Fascin_1 protein could function as a molecular marker for poor prognosis of NSCLC patients. Pelosi et al.[15] analyzed Fascin_1 protein expression in 220 cases of NSCLC in early stage, and positive Fascin_1 expression was observed in 98% of all patients with lung squamous carcinoma and in 78% of all patients with lung adenocarcinoma. The positive expression rate reported in their study was slightly higher than that of in present study. Their study also demonstrated diffuse expression of Fascin_1 in patients with adenocarcinoma who suffered from distant metastasis. However, in patients with squamous cell lung carcinoma, the immunoreactivity intensity of Fascin_1 protein was weaker than that of in keratin pearl, i.e., the expression of Fascin_1 protein was weak. Their follow-up results revealed that the prognosis was usually poor for those patients with diffuse or strongly positive expression of Fascin_1. Their study proved that the expression of Fascin_1 protein was upregulated in invasive lung cancer, andFascin_1 protein may act as an independent prognostic factor for patients with lung cancer. Similarly, this study showed that the NSCLC patients with positive Fascin_1 expression manifested with poor prognosis, and this result was coincided with the findings reported by Pelosi et al.[15]

The findings of both present and previous studies [16],[17],[18],[19],[20] demonstrated that the expression of Fascin_1 protein differed between cancer tissue and paracarcinoma tissues in NSCLC patients and it was also correlated with poor prognosis. Further analysis of Fascin_1 protein expression can be focused on the serum of the patients with NSCLC, as well as exploring the relationship between serum Fascin_1 protein expression level and the patients' prognosis. Fascin_1 protein may become a promising biological marker for predicting the prognosis of NSCLC patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Chen W, Zheng R, Zeng H, Zhang S. Epidemiology of lung cancer in China. Thorac Cancer 2015;6:209-15.  Back to cited text no. 1
[PUBMED]    
2.
Piotrowska Z, Sequist LV. Epidermal growth factor receptor-mutant lung cancer: New drugs, new resistance mechanisms, and future treatment options. Cancer J 2015;21:371-7.  Back to cited text no. 2
[PUBMED]    
3.
Carrizosa DR, Mileham KF, Haggstrom DE. New targets and new mechanisms in lung cancer. Oncology (Williston Park) 2013;27:396-404.  Back to cited text no. 3
[PUBMED]    
4.
Sedeh RS, Fedorov AA, Fedorov EV, Ono S, Matsumura F, Almo SC, et al. Structure, evolutionary conservation, and conformational dynamics of Homo sapiens fascin-1, an F-actin crosslinking protein. J Mol Biol 2010;400:589-604.  Back to cited text no. 4
[PUBMED]    
5.
Wang CQ, Tang CH, Chang HT, Li XN, Zhao YM, Su CM, et al. Fascin-1 as a novel diagnostic marker of triple-negative breast cancer. Cancer Med 2016;5:1983-8.  Back to cited text no. 5
    
6.
Tu L, Xu J, Wang M, Zhao WY, Zhang ZZ, Zhu CC, et al. Correlations of fascin-1 and cadherin-17 protein expression with clinicopathologic features and prognosis of patients with gastric cancer. Tumour Biol 2016;37:8775-82.  Back to cited text no. 6
[PUBMED]    
7.
Hanker LC, Karn T, Holtrich U, Graeser M, Becker S, Reinhard J, et al. Prognostic impact of fascin-1 (FSCN1) in epithelial ovarian cancer. Anticancer Res 2013;33:371-7.  Back to cited text no. 7
[PUBMED]    
8.
Zhao W, Gao J, Wu J, Liu QH, Wang ZG, Li HL, et al. Expression of fascin-1 on human lung cancer and paracarcinoma tissue and its relation to clinicopathological characteristics in patients with lung cancer. Onco Targets Ther 2015;8:2571-6.  Back to cited text no. 8
[PUBMED]    
9.
Adams JC. Roles of fascin in cell adhesion and motility. Curr Opin Cell Biol 2004;16:590-6.  Back to cited text no. 9
[PUBMED]    
10.
Ono S, Yamakita Y, Yamashiro S, Matsudaira PT, Gnarra JR, Obinata T, et al. Identification of an actin binding region and a protein kinase C phosphorylation site on human fascin. J Biol Chem 1997;272:2527-33.  Back to cited text no. 10
[PUBMED]    
11.
Adams JC, Clelland JD, Collett GD, Matsumura F, Yamashiro S, Zhang L, et al. Cell-matrix adhesions differentially regulate fascin phosphorylation. Mol Biol Cell 1999;10:4177-90.  Back to cited text no. 11
    
12.
Al-Alwan MM, Rowden G, Lee TD, West KA. Fascin is involved in the antigen presentation activity of mature dendritic cells. J Immunol 2001;166:338-45.  Back to cited text no. 12
[PUBMED]    
13.
Yang L, Teng Y, Han TP, Li FG, Yue WT, Wang ZT, et al. Clinical significance of fascin-1 and laminin-5 in non-small cell lung cancer. Genet Mol Res 2017;16:1-10.  Back to cited text no. 13
    
14.
Ling XL, Zhang T, Hou XM, Zhao D. Clinicopathological significance of fascin-1 expression in patients with non-small cell lung cancer. Onco Targets Ther 2015;8:1589-95.  Back to cited text no. 14
[PUBMED]    
15.
Pelosi G, Pastorino U, Pasini F, Maissoneuve P, Fraggetta F, Iannucci A, et al. Independent prognostic value of fascin immunoreactivity in stage I nonsmall cell lung cancer. Br J Cancer 2003;88:537-47.  Back to cited text no. 15
[PUBMED]    
16.
Puppa G, Maisonneuve P, Sonzogni A, Masullo M, Chiappa A, Valerio M, et al. Independent prognostic value of fascin immunoreactivity in stage III-IV colonic adenocarcinoma. Br J Cancer 2007;96:1118-26.  Back to cited text no. 16
[PUBMED]    
17.
Liu X, Hao Y, Fan T, Nan K. Application of intelligent algorithm in the optimization of novel protein regulatory pathway: Mechanism of action of gastric carcinoma protein p42.3. J Cancer Res Ther 2016;12:650-6.  Back to cited text no. 17
[PUBMED]    
18.
Natarajan C, Takeda K. Regulation of various DNA repair pathways by E3 ubiquitin ligases. J Cancer Res Ther 2017;13:157-69.   Back to cited text no. 18
[PUBMED]    
19.
Kuribayashi K, Funaguchi N, Nakano T. Chemotherapy for advanced non-small cell lung cancer with a focus on squamous cell carcinoma. J Cancer Res Ther 2016;12:528-34.  Back to cited text no. 19
[PUBMED]    
20.
Tatli AM, Arslan D, Uysal M, Goksu SS, Gunduz SG, Coskun HS, et al. Retrospective analysis of third-line chemotherapy in advanced non-small cell lung cancer. J Cancer Res Ther 2015;11:805-9.  Back to cited text no. 20
[PUBMED]    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  >Abstract>Introduction>Methods>Results>Discussion>Article Figures>Article Tables
  In this article
>References

 Article Access Statistics
    Viewed733    
    Printed5    
    Emailed0    
    PDF Downloaded23    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]