Decreased expression of ING2 gene and its clinicopathological significance in Chinese NSCLC patients

Abstract

The inhibitor of growth 2 (ING2) is a member of ING family, involved in cell cycle regulation, DNA repair, apoptosis and senescence, and participating in chromatin remodeling and transcriptional regulation by histone modification. Recent researches suggest ING2 plays roles in carcinogenesis both as tumor suppressor gene and ongocene depending on tumor types and cell status. Here, we investigated the status of ING2 in a series of 64 Chinese non-small cell lung cancer (NSCLC) patients using immunohistochemistry (IHC) and confirmed the results with Western blotting. RT-PCR results revealed the expression level of ING2 was consistent with mRNA level. The IHC results showed that ING2 protein expression was significantly decreased in NSCLC samples compared with normal lung tissues (P<0.05). ING2 expression was lost in 32.8% (21/64) NSCLC tissues, which was more frequently in adenocarcinoma (ADK) than in squamous cell carcinoma (SCC), 45.8% (11/24) and 26.3% (10/38), respectively. We also found ING2 translocation from the nucleus to the cytoplasm, which may be a critical event for carcinogenesis. And the status of ING2 in SCC was significantly associated with lymph node metastasis status and TNM stage. After sequencing ING2 gene, we found no heterozygosity or mutation. Taken together, these results indicated that the aberrantly expression of ING2 may contribute to NSCLC tumorigenesis. Key words: inhibitor of growth 2, non-small cell lung cancer, pathologyLung cancer remains the leading cause of cancer-related deaths worldwide [1]. Early diagnosis with surgical resection has a 67% 5-year survival [2]. However, the total 5-year survival rate of lung cancer cases was less than 17% [1], due to the lack of sensitive screening tests for early detection of lung cancer and ineffective treatment for advanced and metastatic disease [3]. Non-small-cell lung carcinoma (NSCLC) accounts for approximately 80% to 85% of all lung cancers. The development of NSCLC is a complex progress associated with multiple factors and stages, including accumulation of activation of oncogenes and inactivation of tumor suppressor genes [4]. Although several molecular predictors are being identified involving in lung tumorgenesis, others remain to be discovered [5]. Further researches on suppressor genes, apoptosis-related genes, and autophagy-related genes in the tumor progression of NSCLC will contribute to new strategies for early diagnosis, prognostic indictors and treatment of NSCLC [6].The inhibitor of growth family member 2 (ING2) was identified as a candidate of tumor suppressor by computational homology search with ING1 in 1998, mapped to chromosome 4q35.1 and localized to the subtelomeric region of chromosome 4 [7]. ING2 is comprised of three exons, exon 1a, 1b and 2, which encodes two isoforms, ING2a and ING2b, resulting from an alternative splicing between exons 1a and 1b [8]. The expression level of ING2b mRNA is much lower than ING2a, and ING2b protein has never been detected [9]. ING2a also called ING2 and ING1L, encodes a 33kDa protein ...

RETRACTED: miR-153-3p Suppresses Inhibitor of Growth Protein 2 Expression to Function as Tumor Suppressor in Acute Lymphoblastic Leukemia

“…[16][17][18][19] Pan et al found ING2 message RNA and protein expression level was decreased in non-small cell lung cancer. 17 They also observed translocation of ING2 from nucleus to cytoplasm, which might be a critical event for tumorigenesis. 17 Decreased ING2 expression was also discovered in osteosarcoma, and the loss expression of ING2 was a predictor for poor overall survival of osteosarcoma patients.…”

The Biological and Clinical Relevance of Inhibitor of Growth (ING) Genes in Non-Small Cell Lung Cancer

“…Moreover, this study revealed a significant association between ING2 expression, lymph node metastasis, and TNM stage, albeit only for SCC and not for AC. According to this research study, ING2 is aberrantly expressed in NSCLC and is likely to contribute to lung carcinogenesis [25]. Down-regulation of ING2 protein expression was also confirmed by immunohistochemical analysis on 120 NSCLC specimens [26].…”

“…An immunohistochemical study by Pan et al was conducted in order to analyze the role of ING2 in lung carcinogenesis [25]. Sixty-four samples of NSCLC were tested for ING2 protein expression by means of immunohistochemistry, and the results were confirmed by Western blotting.…”

“…Additionally, RT-PCR was used to evaluate ING2 mRNA levels as well. ING2 protein expression was found to be significantly decreased in this cohort of Chinese NSCLC patients [25], when compared to samples of normal lung tissue. ING2 was more frequently lost in AC (45.8%) than in SCC (26.3%).…”

Exploiting ING2 Epigenetic Modulation as a Therapeutic Opportunity for Non-Small Cell Lung Cancer

“…Another study, conducted on Chinese patient specimens, showed that the ING2 expression was lost in 21 of 64 (32.8%) NSCLC and more frequently in ADK than in SCC (45.8% and 26.3%, respectively) (Table 1). ING2 loss was correlated with lymph node metastasis status and TNM stage in squamous cell carcinoma, but not in adenocarcinome [63]. Whether these discrepancies between these two studies are due to antibody specificity or ethnic disparities (notably, oncogenic driver mutational status was unknown in both studies), remains to be elucidated.…”