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. 2017 Aug;14(2):2453-2457.
doi: 10.3892/ol.2017.6450. Epub 2017 Jun 21.

Association between the expression of inhibitor of growth family member 4 and the progression of clear cell renal carcinoma

Yuxin Ren  1 , Song Zhao  2 , He Chen  3 , Ying-Mei Fu  4 , Bai Zhao  5
Affiliations

Association between the expression of inhibitor of growth family member 4 and the progression of clear cell renal carcinoma

Yuxin Ren et al. Oncol Lett. 2017 Aug.

Abstract

Inhibitor of growth family member 4 (ING4) is a candidate tumor suppressor that serves important roles in tumor growth and angiogenesis. In the present study ING4 expression was assessed in clear cell renal carcinoma (CCRC) tissues and its association with the progression of CCRC was determined. The expression of ING4 in 125 patients with CCRC was analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analysis and immunohistochemical methods. A total of 40 adjacent normal renal tissues were used as control samples. The results identified that ING4 expression was positive in 100% of normal renal tissues, but in only 82.3% CCRC samples. RT-qPCR and western blotting results demonstrated that expression levels of ING4 mRNA and protein were significantly decreased in CCRC compared with in normal tissues (P<0.0001). ING4 expression was not associated with sex, age or tumor volume (P>0.05), but was associated with the nuclear grade of renal cancer (P<0.0001), the clinical stage of CCRC (P<0.0001) and lymphatic metastasis (P<0.0001). The results of the present study indicated that dysregulation of ING4 expression may be involved in the initiation and progression of CCRC.

Keywords: clear cell renal carcinoma; clinical stage; inhibitor of growth family member 4; lymphatic metastases; tumor suppressor.

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Figures

Figure 1.
Figure 1.
ING4 mRNA is significantly decreased in CCRC tissues when compared with normal renal tissues. (A) A total of 40 paired tumor and adjacent normal renal tissues were analyzed for ING4 mRNA level by reverse transcription-quantitative polymerase chain reaction. β-actin was used as an internal control. (B) Analysis of relative mRNA level (compared with normal renal tissue) according to Fuhrman nuclear grade (24) (grade I, n=7; grade II, n=16; grade 3, n=13; grade 4, n=4), lymphatic metastasis (n0, n=29; n1, n=7; n2, n=4), tumor clinical stage (stage I, n=9; stage II, n=12; stage III, n=14; stage IV, n=5). ***P<0.001 by t-test. CCRC, clear cell renal carcinoma; ING4, inhibitor of growth family member 4.
Figure 2.
Figure 2.
ING4 expression is significantly decreased in CCRC tissues when compared with normal renal tissues. (A) A total of 40 paired tumor and adjacent normal renal tissues were analyzed for ING4 expression using western blotting. Decreased ING4 expression was observed in CCRC tissues compared with adjacent normal renal tissues. β-actin was used as internal control. (B) Average ING4 expression in 40 paired tumor and normal renal tissues samples. (C) Analysis of the expression level of ING4 protein (compared with normal renal tissue) according to tumor nuclear grade (grade I, n=7; grade II, n=16; grade III, n=13; grade IV, n=4), lymphatic metastasis (n0, n=29; n1, n=7; n2, n=4), tumor clinical stage (stage I, n=9; stage II, n=12; stage III, n=14; stage IV n=5). ***P<0.001 by t-test. CCRC, clear cell renal carcinoma; ING4, inhibitor of growth family member 4; NT, normal tissue.
Figure 3.
Figure 3.
ING4 protein expression detected using the EnVision system in (A) normal renal tubular epithelial cell nuclei, and in renal cell carcinoma; (B) nuclear grade I, cellular expression; (C) nuclear grade II, cell membrane and cytoplasmic expression; (D) nuclear grade III, cytoplasmic expression; (E) nuclear grade IV, cytoplasmic expression; (F) positive expression of cytoplasmic granules. Magnification of all images, ×400. ING4, inhibitor of growth family member 4.
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