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


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2013  |  Volume : 9  |  Issue : 5  |  Page : 98-100

Association between clinical pathology and multiple genes mRNA expression in Chinese patients with NSCLC


Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China

Date of Web Publication30-Sep-2013

Correspondence Address:
Gang Chen
Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, 300052
China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.119118

Rights and Permissions
 > Abstract 

Objective: The aim of this study was to evaluate whether there was an association between pathology type and ERCC1, BRCA1, RRM1, TUBB3, STMN1, TOP2A and epidermal growth factor receptor (EGFR) messenger ribonucleic acid (mRNA) expression level in Chinese patients with non-small cell lung carcinoma (NSCLC).
Materials and Methods: mRNA expression level of these genes was analyzed in 181 cancer tissues by using xTAG-step liquid-chip array. The mRNA expression level of the seven genes was evaluated in association with the clinical pathology type.
Results: The average mRNA expression level of the seven genes were ERCC1 (1.02 ± 0.03), BRCA1 (0.15 ± 0.04), RRM1 (0.19 ± 0.05), TUBB3 (0.31 ± 0.06), STMN1 (2.78 ± 0.42), TOP2A (3.04 ± 0.42) and EGFR (0.58 ± 0.09), respectively in Chinese patients with NSCLC. The mRNA expression level of ERCC1, STMN1 and TOP2A genes were statistical different with different pathology type (p a < 0.05); STMN1 and TOP2A genes mRNA expression were much higher in squamous cell lung carcinoma than that in non-squamous cell lung carcinoma (p a < 0.05). And ERCC1 gene expression was much lower in squamous cell carcinoma than that in non-squamous cell carcinoma (p a < 0.05).
Conclusion: mRNA expression level of STMN1, TOP2A and ERCC1 were correlated with the clinical pathology type.

Keywords: Clinical pathology, messenger ribonucleic acid expression, non-small cell lung carcinoma


How to cite this article:
Chen G, Jundong G U, Chen J, Liu Y, Song Z. Association between clinical pathology and multiple genes mRNA expression in Chinese patients with NSCLC. J Can Res Ther 2013;9, Suppl S1:98-100

How to cite this URL:
Chen G, Jundong G U, Chen J, Liu Y, Song Z. Association between clinical pathology and multiple genes mRNA expression in Chinese patients with NSCLC. J Can Res Ther [serial online] 2013 [cited 2019 May 19];9:98-100. Available from: http://www.cancerjournal.net/text.asp?2013/9/5/98/119118


 > Introduction Top


Lung cancer is the leading cause of cancer related death in China. [1] Recently, the combined chemotherapy of third generation cell toxicity drug and platinum become new standard regimen for non-small cell lung carcinoma (NSCLC). However, the objective response rate for these drugs was only about 30% and the reasons for resistance were not completely clear. The understanding molecular mechanism for resistance to chemotherapeutic drugs was important. Changes of tumor suppressor gene mRNA expression may lead impact of treatment and prevention of NSCLC. [2] And certain gene expression level was correlated with the prognosis in breast and liver cancer. [3],[4] Therefore, in this study, we use xTAG - step liquid-chip technology to examine the mRNA expression of ERCC1, BRCA1, RRM1, TUBB3, STMN1, TOP2A and epidermal growth factor receptor (EGFR) in Chinese patients with NSCLC.


 > Materials and Methods Top


Patients data collection

From October 2009 to June 2012, 181 formalin-fixed paraffin-embedded (FFPE) specimens of non-small cell lung cancer tissue were collected from patients who received the operation for lung cancer in the department of lung tumor surgery of Tianjin university general hospital. Patients inclusion criteria were: age ≥ 18 years; pathology type of NSCLC; without preoperative chemoradiation or EGFR-tyrosine kinase inhibitor treatment; all patients included in these study signed the informed consent. And the clinical characteristics of ages, gender and pathology type were recorded.

mRNA expression level examination

The detection of RNA expression was conducted by SurExam Bio-Tech Co. Ltd. FFPE tissue samples were processed by following steps. First the sample was homogenized in a mixture of homogenizing solution at 65°C for 2 h. The homogenate was centrifuged to remove residual paraffin and debris and then the supernatant was transferred to a fresh microcentrifuge tube. A test dose of 40 μl sample homogenate were added to each well of a 96-well plate that contains following reagents in each well: 18.5 μl of RNase-free water, 33.3 μl of lysis solutions, 2 μl of blocking reagent, 1 μl of capture beads and 5 μl of target gene-specific probe set. The plate was sealed and incubated for 18 h at 54°C on a shaker with 750 rpm. The hybridization mixture was then removed to a filtered 96-well plate. The un-bound RNA and other debris in wells were removed by washing three times with 250 μl of wash buffer (0.1× SSC and 0.03% lithium lauryl sulfate) under a vacuum system. Signals for the bound target mRNA were developed by following steps: (1) Incubate in 100 μl of pre-amplifier solution for 1 h at 50°C; (2) wash twice with 200 μl wash buffer; (3) incubate in 100 μl of amplifier solution for 1 h at 50°C; (4) wash twice with 200 μl wash buffer; (5) incubate in 100 μl of the labeled probe for 1 h at 50°Cand (6) wash twice with 200 μl wash buffer. The samples were then developed with 100 μl SA-PE solution at 50°C for 30 min. The fluorescence value of each sample was analyzed by the Lumine × 200 system.

Statistical analysis

All data was analyzed by using STATA/SE 11.0 (Stata Corp LP, http://www.stata.com)statistic software. The mRNA expression level of these genes were demonstrated as mean ± standard deviation, The correlation of gene mRNA expression with clinical pathology type was evaluated by Student's test. A significance level of both sides P < 0.05 was used.


 > Results Top


mRNA expression level of these genes

The average mRNA expression level of the eight genes were ERCC1 (1.02 ± 0.03), BRCA1 (0.15 ± 0.04), RRM1 (0.19 ± 0.05), TUBB3 (0.31 ± 0.06), STMN1 (2.78 ± 0.42), TOP2A (3.04 ± 0.42) and EGFR (0.58 ± 0.09), respectively in Chinese patients with non-small cell lung [Table 1].
Table 1:

Click here to view


Correlation between mRNA expression and clinical pathology

The mRNA expression level of ERCC1, STMN1 and TOP2A genes were statistical different with different pathology type (p a < 0.05); STMN1 and TOP2A genes mRNA expression were much higher in squamous cell lung carcinoma than that in non-squamous cell lung carcinoma (p a < 0.05). And ERCC1 gene expression was much lower in squamous cell carcinoma than that in non-squamous cell carcinoma (p a < 0.05), [Figure 1].
Figure 1: Messenger ribonucleic acid expression between different pathology type

Click here to view



 > Discussion Top


Accounting for 13% (1.6 million) of the total cases and 18% (1.4 million) of the deaths, lung cancer was the most commonly diagnosed cancer as well as the leading cause of cancer death world-wide in 2008. [5] Recently, the cancer suppressor genes mRNA expression level was consider as associated with the chemotherapy efficacy. [6] Therefore, it is important to evaluate these genes expression level before treatment with chemotherapy. In this study, we analyzed the mRNA expression level of seven cancer suppressor genes by using xTAG-step liquid-chip array in Chinese patients with NSCLC. We found that the average mRNA expression level of the seven genes were ERCC1 (1.02 ± 0.03), BRCA1 (0.15 ± 0.04), RRM1 (0.19 ± 0.05), TUBB3 (0.31 ± 0.06), STMN1 (2.78 ± 0.42), TOP2A (3.04 ± 0.42) and EGFR (0.58 ± 0.09), respectively. And mRNA expression level of ERCC1, STMN1 and TOP2A genes were statistical different with different pathology type (p a < 0.05); STMN1 and TOP2A genes mRNA expression were much higher in squamous cell lung carcinoma than that in non-squamous cell lung carcinoma (p a < 0.05). And ERCC1 gene expression was much lower in squamous cell carcinoma than that in non-squamous cell carcinoma (p a < 0.05).

ERCC1 is the 5'endonuclease of the nucleotide excision repair complex gene. Its mRNA expression levels vary a lot in different type of cancers. In NSCLC, ERCC1 mRNA expression level was considered as the prognostic marker in patients who did not receive the preoperative treatment. And some studies demonstrated that ERCC1 expression level is associated with the clinical efficacy of platinum-based chemotherapy in patients with non-small cell lung. But, the association between ERCC1 and clinical pathology is not clear. In our study, we found that ERCC1 gene expression was much lower in squamous cell carcinoma than that in non-squamous cell carcinoma, which demonstrated that the squamous cell carcinoma of the lung may sensitive to the platinum-based chemotherapy than that with non-squamous cell carcinoma.

STMN1 (the official symbol for stathmin or oncoprotein-18) is one of the cellular proteins that destabilize microtubules in a phosphorylation-dependent manner. [7],[8] Some studies have demonstrated that STMN1 played an important role in cell cycle progression and cell migration. [9] In colon cancer cells, STMN1 was deemed as a molecular biomarker for therapeutic regiments for its ability of signature for an activation of the phosphatidylinositol 3-kinase/AKT pathway. [10] STMN1 mRNA expression level was evaluated in various kinds of cancers including lung cancer. And its expression level was correlated with the prognosis in breast and liver cancer. [3],[4] However, whether its expression was associated with the outcome and clinical characteristics of NSCLC in not clear. [11] In this study, we found that STMN1 mRNA expression were much higher in squamous cell lung carcinoma than that in non-squamous cell lung carcinoma (p a < 0.05). This was the first time to describe the relationship between STMN1 expression level and clinical pathology types in patients with NSCLC according to the literature. However, the association between STMN1 expression and prognosis of NSCLC patients was not evaluated for lack of enough follow-up data.

In the present study, we assess the association between multiple gene mRA expression level and clinical pathology types in patients with NSCLC. And we found that STMN1 and TOP2A genes mRNA expression were much higher in squamous cell lung carcinoma than that in non-squamous cell lung carcinoma and ERCC1 gene expression was much lower in squamous cell carcinoma than that in non-squamous cell carcinoma. This indicated that mRNA expression level of STMN1, TOP2A and ERCC1 were correlated with the clinical pathology type. However by virtue of lacking enough follow-up data, the association between their expression and survival was not evaluated.

 
 > References Top

1.Chen WQ, Zheng RS, Zeng HM. Bayesian age-period-cohort prediction of lung cancer incidence in China. Thorac Cancer 2011;2:149-55.  Back to cited text no. 1
    
2.Leng XF, Chen MW, Xian L, Dai L, Ma GY, Li MH. Combined analysis of mRNA expression of ERCC1, BAG-1, BRCA1, RRM1 and TUBB3 to predict prognosis in patients with non-small cell lung cancer who received adjuvant chemotherapy. J Exp Clin Cancer Res 2012;31:25.  Back to cited text no. 2
[PUBMED]    
3.Yuan RH, Jeng YM, Chen HL, Lai PL, Pan HW, Hsieh FJ, et al. Stathmin overexpression cooperates with p53 mutation and osteopontin overexpression, and is associated with tumour progression, early recurrence, and poor prognosis in hepatocellular carcinoma. J Pathol 2006;209:549-58.  Back to cited text no. 3
[PUBMED]    
4.Golouh R, Cufer T, Sadikov A, Nussdorfer P, Usher PA, Brünner N, et al. The prognostic value of Stathmin-1, S100A2, and SYK proteins in ER-positive primary breast cancer patients treated with adjuvant tamoxifen monotherapy: An immunohistochemical study. Breast Cancer Res Treat 2008;110:317-26.  Back to cited text no. 4
    
5.Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin 2009;59:225-49.  Back to cited text no. 5
[PUBMED]    
6.Hu Q, Li B, Garfield D, Ren S, Li A, Chen X. Prognostic factors for survival in a Chinese population presenting with advanced non-small cell lung cancer with an emphasis on smoking status: A regional, single-institution, retrospective analysis of 4552 patients. Thoracic Cancer 2012;3:162-8.  Back to cited text no. 6
    
7.Steinmetz MO. Structure and thermodynamics of the tubulin-stathmin interaction. J Struct Biol 2007;158:137-47.  Back to cited text no. 7
[PUBMED]    
8.Nogales E, Wang HW. Structural intermediates in microtubule assembly and disassembly: How and why? Curr Opin Cell Biol 2006;18:179-84.  Back to cited text no. 8
[PUBMED]    
9.Johnsen JI, Aurelio ON, Kwaja Z, Jörgensen GE, Pellegata NS, Plattner R, et al. p53-mediated negative regulation of stathmin/Op18 expression is associated with G (2)/M cell-cycle arrest. Int J Cancer 2000;88:685-91.  Back to cited text no. 9
    
10.Saal LH, Johansson P, Holm K, Gruvberger-Saal SK, She QB, Maurer M, et al. Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Proc Natl Acad Sci U S A 2007;104:7564-9.  Back to cited text no. 10
[PUBMED]    
11.Okamoto T, Wada H, Mizobuchi T, Hoshino H, Moriya Y, Yoshida S, et al. Prognostic impact of cell type under the seventh TNM staging system in resected non-small cell lung cancer. Thorac Cancer 2012;3:249-54.  Back to cited text no. 11
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1]



 

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>Materials and Me...>Results>Discussion>Article Figures>Article Tables
  In this article
>References

 Article Access Statistics
    Viewed1465    
    Printed67    
    Emailed0    
    PDF Downloaded93    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]