HDAC10 expression is associated with DNA mismatch repair gene and is a predictor of good prognosis in colon carcinoma

  • Authors:
    • Xiangxiang Tao
    • Yifeng Yan
    • Linming Lu
    • Bing Chen
  • View Affiliations

  • Published online on: August 24, 2017     https://doi.org/10.3892/ol.2017.6818
  • Pages: 4923-4929
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Despite increasing evidence of the involvement of histone deacetylase (HDAC)10 in cancer tumorigenesis, the potential role of HDAC10 in colon cancer remains unclear. Oncomine database analysis revealed that HDAC10 mRNA was significantly upregulated in colon cancer. In an independent cohort, consistent with mRNA expression levels, constitutively high HDAC10 expression was observed in the cytoplasm and nucleus compared with in adjacent normal tissues (cytoplasm, 93.12±12.98 vs. 31.65±26.50%; nucleus, 84.16±19.23 vs. 68.64±19.00%). Cytoplasmic HDAC expression correlated with gender (r=0.265; P<0.05), lymph node metastasis (N stage; r=0.256; P<0.05) and distant metastasis (M stage; r=0.331; P<0.05) in paracarcinoma tissues. Cytoplasmic HDAC10 expression in tumors was not associated with the four DNA mismatch repair genes examined, but was negatively correlated with mutL homolog 1 (MLH1) (r=‑0.244; P<0.05), mutS homolog (MSH)2 (r=‑0.410; P<0.01) and MSH6 (r=‑0.240; P<0.05) in paracarcinoma tissues. Similarly, nuclear HDAC10 expression was negatively correlated with MLH1 expression (r=‑0.288; P<0.05). The findings of the current study suggest that HDAC10 expression is associated with good prognosis in colon cancer tissues and poor prognosis in paracarcinoma tissues with a potential involvement in DNA mismatch repair.

Introduction

Histone deacetylases (HDACs) was the name originally given to a family of proteins responsible for deacetylation of histone proteins, which were later shown to be also involved in the deacetylation of non-histone proteins (1,2). HDACs are divided into four classes based on structure: Class I including HDAC1, HDAC2, HDAC3 and HDAC8; class II, which is further divided into class IIa (HDAC4, HDAC5, HDAC7 and HDAC9) and class IIb (HDAC6 and HDAC10); class III comprising SIRT1 to SIRT7; and class IV, consisting of only HDAC11. While HDAC6 is a well-investigated class II HDAC, little is known about HDAC10.

HDAC10 has been reported to be involved in homologous recombination (3), melanogenesis (4), cells autophagy (57), cell cycle regulation (8), DNA mismatch repair (9) and cancer progression (1016). While HDAC10 was reported to suppresses the proliferation and invasion of clear cell renal cell carcinoma (13), it was also demonstrated to promote cell proliferation via AKT phosphorylation in lung cancer (15). Based on these contradictory observations, we hypothesized that the function of HDAC10 in cancer is more complex and may be dependent on the type of tissue.

Colorectal carcinoma is among the five most commonly diagnosed cancers accounting for over 50% of the top five cancers all cases in China (17). Owing to the high risk of relapse and metastasis, the treatment for advanced colon cancer poses a significant challenge. Thus, it is crucial to discover new and competent therapeutic targets for colon cancer, thereby enabling the discovery of new diagnostic and therapeutic drugs.

To date, the expression of HDAC10, especially the prognostic role and its association with clinicopathological features in colon cancer has not been investigated. In this study we analyzed 100 colon cancer specimens in a tissue microarray (TMA) to assess HDAC10 expression and to evaluate the clinical significance of HDAC10 in colon cancer.

Patients and methods

Patients

A total of 100 colon cancer patients (54 male, 45 female and one missed gender information) aged between 24 and 90 were recruited in this study. All patients underwent surgery during July 2006 to May 2007 and received no prior extra therapy. Of these, 6 were cTNM stage I, 54 were cTNM stage II, 35 were cTNM stage III, and 3 were cTNM stage IV according to AJCC. Following surgery, a long-term follow-up was implemented for all patients up to July 2015. During the follow-up time, 61 patients died of colon carcinoma with a median overall survival time of 26 months. Detailed patient information is listed in Table I.

Table I.

Clinical parameters of colon carcinoma patients.

Table I.

Clinical parameters of colon carcinoma patients.

Clinical factorsNo. of patients
Gender
  Male54
  Female45
Age
  ≤6021
  >6073
Tumor size
  ≤5 cm55
  >5 cm43
Pathological grade
  12
  248
  350
T stage
  T1+T27
  T3+T489
N stage
  N060
  N127
  N211
M stage
  M097
  M13
cTNM stage
  16
  254
  335
  43
Tumor location
  Right61
  Left38
Immunohistochemistry

Colon adenocarcinoma TMA (HColA180Su09) containing 100 tumor tissues and 80 paired adjacent tissues was obtained from Shanghai Outdo Biotech Co., Ltd. (Shanghai, China) for standardization. Deparaffinization of the TMA was performed by xylene and graded alcohol following incubation at high temperature for an hour. After antigen retrieval by EDTA and blocking with goat serum, the TMA was incubated with the primary anti-HDAC10 antibody (24913-1-AP) obtained from ProteinTech Group, Inc. (Chicago, IL, USA) at a dilution of 1:2,500 at 4°C overnight, and subsequently incubated with horse radish peroxidase (HRP) labeled secondary-antibody (K8000; Dako; Agilent Technologies, Inc., Santa Clara, CA, USA) for 30 min. Diaminobenzidine (DAB) and hematoxylin redyeing were performed for visualization. Three random fields having more than 100 cells were visually analyzed and scored by pathologists. The colon cancer patients were divided into three subgroups based on differences in HDAC10 expression as follows: 0–60%, low expression; 61–90%, median expression; 91–100%, high expression. The expression of mutL homolog 1 (MLH1) (1:5,000, sc-56160; Santa Cruz Biotechnology, Inc., Dallas, TX, USA), mutS homolog (MSH)2 (1:100, sc-56163; Santa Cruz Biotechnology, Inc.), MSH6 (1:5,000, 66172-1-Ig; ProteinTech Group, Inc.) and PMS2 (1:1,500, sc-618; Santa Cruz Biotechnology, Inc.) was also detected in these patients with the same protocol. The specificity of the anti-HDAC10 antibody used in the present study was validated by Wang et al in a previous study (18).

Statistical analysis

The difference in HDAC10 expression between colon adenocarcinoma and adjacent tissues was evaluated by paired t-test. Spearman's rank correlation coefficient and two-tailed test were performed to evaluate the correlation between HDAC10 expression and clinical parameters. Pearson analysis was performed to assess the association between HDAC10 and MLH1/MSH2/MSH6/PMS2 expression. Based on HDAC10 and clinical parameters, overall survival curves were drawn according to the Kaplan-Meier method and log-rank test. Subsequently, COX multivariate regression survival analysis was performed to determine the independent prognostic marker. All statistical analyses were conducted using SPSS 17.0 software (SPSS, Inc., Chicago, IL, USA), with P<0.05 being considered significant.

Results

Evaluation of HDAC10 mRNA expression in colon carcinoma

The HDAC10 mRNA expression level in colon adenocarcinoma was investigated in the Oncomine database. As depicted in Fig. 1, HDAC10 mRNA expression in colon adenocarcinoma tissues was found to be significantly upregulated both in the Kaiser colon statistics involving 41 colon carcinoma tissues and 5 normal tissues (fold change=1.103, P<0.05; Fig. 1A) as well as in the TCGA colorectal database containing 101 colon adenocarcinoma tissues and 19 normal colon tissues (fold change=1.656, P=1.07e-7; Fig. 1B).

HDAC10 expression is high in colon carcinoma

To investigate HDAC10 expression in colon adenocarcinoma, two-step immunohistochemistry was performed on the TMA. As shown in Fig. 2, constitutively high HDAC10 expression was visualized both in the cytoplasm and nucleus in most colon cancer tissues when compared with the adjacent normal tissues. Subsequently, HDAC10 expression in colon cancer was systemically investigated by statistical analysis with the adjacent normal tissue as a control (cytoplasm, 93.12±12.98 vs. 31.65±26.50%; Fig. 2C; nucleus, 84.16±19.23 vs. 68.64±19.00%; Fig. 2D). The results indicated significantly elevated expression of HDAC10 protein at the tissue level. Regardless of the location, HDAC10 expression did not show a significant correlation with the tumor tissue when compared with the adjacent normal tissue (Table I). Interestingly, HDAC10 expression in the nucleus was associated with its cytoplasmic expression, both in the tumor tissue as well as in the adjacent normal tissue (Table II).

Table II.

Correlation between HDAC10 expression in tumor and para-carcinoma tissues.

Table II.

Correlation between HDAC10 expression in tumor and para-carcinoma tissues.

CytoplasmNucleus


LocationTissueTumorPara-carcinomaTumorPara-carcinoma
CytoplasmTumor
  Pearson correlation10.1000.227a−0.107
  Sig. (2-tailed) 0.3870.0240.356
  Number98779877
Para-carcinoma
  Pearson correlation0.100  1−0.0940.333b
  Sig. (2-tailed)0.387 0.4160.003
  Number77797779
NucleusTumor
  Pearson correlation0.227a−0.094  10.037
  Sig. (2-tailed)0.0240.416 0.747
  Number98779877
Para-carcinoma
  Pearson correlation−0.1070.333b0.0371
  Sig. (2-tailed)0.3560.0030.747
  Number77797779

a Correlation is significant at the 0.05 level (2-tailed).

b Correlation is significant at the 0.01 level (2-tailed). HDAC10, histone deacetylase 10.

Correlation between HDAC10 expression and clinical parameters

HDAC10 expression in colon adenocarcinoma tissues showed no significant correlation with any clinicopathological factors, apart from a link between cytoplasmic HDAC expression and gender (r=0.265, P<0.05). Intriguingly however, HDAC10 expression in para-carcinoma tissues was highly associated with clinicopathological factors. Cytoplasmic HDAC10 expression was found to be positively correlated with lymph node metastasis (N stage, r=0.256, P<0.05) and distant metastasis (M stage, r=0.331, P<0.05). Detailed results of the correlation analysis are listed in Table III.

Table III.

Association between HDAC10 and clinical parameters in colon adenocarcinoma.

Table III.

Association between HDAC10 and clinical parameters in colon adenocarcinoma.

HDAC10 expression

LocationTissueGenderAgeTumor sizePathological gradeTNMcTNMTumor location
CytoplasmTumor
  Correlation0.1940.1080.025−0.181−0.0300.1460.0870.1010.001
  Coefficient
  Sig. (2-tailed)0.0570.3050.8110.0740.7730.1570.3950.3260.996
  Number979296989496989697
Para-carcinoma
  Correlation0.1790.133−0.015−0.095−0.1070.256a0.331b0.180−0.085
  coefficient
  Sig. (2-tailed)0.1180.2590.8990.4030.3560.0240.0030.1150.461
  Number787478797778797878
NucleusTumor
  Correlation0.265b0.1000.199−0.0070.0590.073−0.0820.065−0.046
  Coefficient
  Sig. (2-tailed)0.0090.3440.0520.9460.5710.4770.4210.5290.655
  Number979296989496989697
Para-carcinoma
  Correlation0.119−0.0670.0450.119−0.0900.2070.0750.1220.037
  Coefficient
  Sig. (2-tailed)0.3010.5690.6940.2980.4380.0690.5100.2870.746
  Number787478797778797878

a Correlation is significant at the 0.05 level (2-tailed).

b Correlation is significant at the 0.01 level (2-tailed). HDAC10, histone deacetylase 10.

Different prognostic role of HDAC10 in colon carcinoma and para-carcinoma

High cytoplasmic expression of HDAC10 in tumor tissues predicted good prognosis in colon cancer patients, with 0% survival in the population with low HDAC10 expression after 8 years of follow-up, in contrast with 29.4% for population with median expression and 43.0% for population with high expression (Fig. 3A). Conversely, cytoplasmic HDAC10 expression in para-carcinoma tissues was associated with poor outcome of patients (43.3 vs. 20.0 vs. 0%, P<0.001; Fig. 3B). Nuclear HDAC10 expression in the tumor tissues did not correlate with overall increased survival of colon cancer patients (28.6 vs. 40.8 vs. 40.5%, P>0.05; Fig. 3C), while high nuclear HDAC10 expression in the para-carcinoma tissues was correlated with increased survival rate (43.5 vs. 38.9 vs. 0%, P<0.001; Fig. 3D). Furthermore, regional lymph node metastasis (N stage, 51.7 vs. 25.9 vs. 9.1%, P=0.000), distant metastasis (M stage, 40.2 vs. 0.0%, P<0.001), tumor location (right vs. left, 31.1 vs. 52.6%, P<0.05) and clinical stage (cTNM, 66.7 vs. 50.0 vs. 22.9 vs. 0.0%, P<0.001) were all correlated with overall survival time. Subsequent multivariate analysis indicated that only cytoplasmic HDAC10 expression was an independent prognostic marker for colon cancer (Table IV).

Table IV.

Multivariate analysis of factors associated with survival in colon carcinoma.

Table IV.

Multivariate analysis of factors associated with survival in colon carcinoma.

95.0% CI for Exp (B)

FactorsSig.Exp (B)LowerUpper
N stage0.9280.9540.3432.657
M stage0.9860.9810.1098.845
cTNM stage0.1202.3780.7987.086
Tumor location (right vs. left)0.4690.7880.4131.503
Cytoplasmic HDAC10 in tumor0.0930.5390.2621.109
Cytoplasmic HDAC10 in para-carcinoma0.0202.8961.1817.105
Nuclear HD10 in para-carcinoma0.9740.9880.4882.000
HDAC10 may be associated with DNA mismatch repair

The implication of HDAC10 in DNA repair pathway via interaction with DNA mismatch repair gene MSH2 in HeLa cells prompted us to explore the possibility that HDAC10 is involved in the progression of colon cancer via its interaction with the DNA mismatch repair genes (9). Four major DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2 were investigated by immunohistochemistry. Pearson analysis was performed to evaluate the their association with HDAC10. The results, listed in Table V, predicted that cytoplasmic HDAC10 expression in the tumor tissue was not associated with any of the four DNA mismatch repair genes. Instead it showed negative association with MLH1 (r=−0.244, P<0.05), MSH2 (r=−0.410, P<0.001) and MSH6 (r=−0.240, P<0.05) in the para-carcinoma tissues. Similarly, nuclear HDAC10 expression was negatively correlated with MLH1 expression (r=−0.288, P<0.05).

Table V.

Association between HDAC10 expression and expression of DNA mismatch repair genes in colon cancer.

Table V.

Association between HDAC10 expression and expression of DNA mismatch repair genes in colon cancer.

HDAC10 expression

LocationTissueMLH1MSH2MSH6PMS2
CytoplasmTumor
  Pearson correlation−0.072−0.208−0.0710.158
  Sig. (2-tailed)0.5300.0680.5260.165
  Number79788179
Para-carcinoma
  Pearson correlation−0.244a−0.410b−0.240a−0.066
  Sig. (2-tailed)0.0380.0000.0400.580
  Number72717372
NucleusTumor
  Pearson correlation0.1640.1180.230a0.297b
  Sig. (2-tailed)0.1480.3020.0390.008
  Number79788179
Para-carcinoma
  Pearson correlation−0.288a−0.126−0.097−0.031
  Sig. (2-tailed)0.0140.2950.4130.798
  Number72717372

a Correlation is significant at the 0.05 level (2-tailed).

b Correlation is significant at the 0.01 level (2-tailed). HDAC10, histone deacetylase 10.

Discussion

To the best of our knowledge, our findings highlight for the first time, the clinical significance of HDAC10 in colon cancer. HDAC10 was demonstrated to be a tumor suppresser in some types of cancer, including clear cell renal cell carcinoma (13), cervical cancer (19), gastric cancer (12,20), and ovarian cancer (16). The function of HDAC10 in lung cancer is a matter of debate (10,15). High HDAC10 expression was associated with good prognosis in non-small cell lung cancer (10) but has been lately demonstrated to promote lung cancer proliferation (15).

Class II HDACs have been reported to be able to shuttle between the nucleus and cytoplasm. In this study, we found similar behavior of HDAC10 expression in colon cancer tissues. Yang et al reported that HDAC10 is mainly expressed in the cytoplasm of lung cancer cells but is mainly located in the nucleus of normal lung cells, and suggested different functions of cytoplasmic and nuclear HDAC10 in lung cancer progression (15). The association of cytoplasmic and nuclear HDAC10 expression and clinicophathological and prognostic effect is inconsistent even in colon cancer. Moreover, in tumor tissues HDAC10 acted as a tumor suppressor, but showed quite different effect in adjacent tissues, suggesting that HDAC10 might act as a tumor suppressor in colon cancer tissues but may also function as a tumor promoter by promoting tumor metastasis to regional lymph node or to distant tissues.

A growing number of studies point to quite different prognosis of patients between right-sided and left-sided colon cancers (21). The probability of relapse of colon carcinoma in different sides is dependent on different molecular pathways (22). Our observation is consistent with the previous studies that survival of patients with right-sided colon cancer is less than those with left-sided colon cancer.

In summary, our findings suggest that HDAC10 expression in tumor tissues is associated with good prognosis of colon cancers but predicted poor prognostic outcomes in para-carcinoma tissues, probably owing to regulation of the DNA mismatch repair pathway. Further studies by altering the HDAC10 expression in colon cancer cells and normal colon cells to investigate the potential functionin invasion and metastasis is needed to test our notion that HDAC10 has different roles in tumor and para-carcinoma tissues.

Acknowledgements

The present study was supported by Foundation for Key Project of Natural Science Research Education Department of Anhui Province (KJ2016A726 and KJ2017A249).

References

1 

Yuan Z, Peng L, Radhakrishnan R and Seto E: Histone deacetylase 9 (HDAC9) regulates the functions of the ATDC (TRIM29) protein. J Biol Chem. 285:39329–39338. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Clocchiatti A, Florean C and Brancolini C: Class IIa HDACs: From important roles in differentiation to possible implications in tumourigenesis. J Cell Mol Med. 15:1833–1846. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Kotian S, Liyanarachchi S, Zelent A and Parvin JD: Histone deacetylases 9 and 10 are required for homologous recombination. J Biol Chem. 286:7722–7726. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Lai IL, Lin TP, Yao YL, Lin CY, Hsieh MJ and Yang WM: Histone deacetylase 10 relieves repression on the melanogenic program by maintaining the deacetylation status of repressors. J Biol Chem. 285:7187–7196. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Oehme I, Lodrini M, Brady NR and Witt O: Histone deacetylase 10-promoted autophagy as a druggable point of interference to improve the treatment response of advanced neuroblastomas. Autophagy. 9:2163–2165. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Oehme I, Linke JP, Böck BC, Milde T, Lodrini M, Hartenstein B, Wiegand I, Eckert C, Roth W, Kool M, et al: Histone deacetylase 10 promotes autophagy-mediated cell survival. Proc Natl Acad Sci USA. 110:E2592–E2601. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Pinto G, Shtaif B, Phillip M and Gat-Yablonski G: Growth attenuation is associated with histone deacetylase 10-induced autophagy in the liver. J Nutr Biochem. 27:171–180. 2016. View Article : Google Scholar : PubMed/NCBI

8 

Li Y, Peng L and Seto E: Histone deacetylase 10 regulates the cell cycle G2/M phase transition via a novel let-7-HMGA2-cyclin A2 pathway. Mol Cell Biol. 35:3547–3565. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Radhakrishnan R, Li Y, Xiang S, Yuan F, Yuan Z, Telles E, Fang J, Coppola D, Shibata D, Lane WS, et al: Histone deacetylase 10 regulates DNA mismatch repair and may involve the deacetylation of MutS homolog 2. J Biol Chem. 290:22795–22804. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Osada H, Tatematsu Y, Saito H, Yatabe Y, Mitsudomi T and Takahashi T: Reduced expression of class II histone deacetylase genes is associated with poor prognosis in lung cancer patients. Int J Cancer. 112:26–32. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Park BL, Kim YJ, Cheong HS, Lee SO, Han CS, Yoon JH, Park JH, Chang HS, Park CS, Lee HS and Shin HD: HDAC10 promoter polymorphism associated with development of HCC among chronic HBV patients. Biochem Biophys Res Commun. 363:776–781. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Lee JH, Jeong EG, Choi MC, Kim SH, Park JH, Song SH, Park J, Bang YJ and Kim TY: Inhibition of histone deacetylase 10 induces thioredoxin-interacting protein and causes accumulation of reactive oxygen species in SNU-620 human gastric cancer cells. Mol Cells. 30:107–112. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Fan W, Huang J and Xiao H: Histone deacetylase 10 suppresses proliferation and invasion by inhibiting the phosphorylation of β-catenin and serves as an independent prognostic factor for human clear cell renal cell carcinoma. Int J Clin Exp Med. 8:3734–3742. 2015.PubMed/NCBI

14 

Powers J, Lienlaf M, Perez-Villarroel P, Deng S, Knox T, Villagra A and Sahakian E: Expression and function of histone deacetylase 10 (HDAC10) in B cell malignancies. Methods Mol Biol. 1436:129–145. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Yang Y, Huang Y, Wang Z, Wang HT, Duan B, Ye D, Wang C, Jing R, Leng Y, Xi J, et al: HDAC10 promotes lung cancer proliferation via AKT phosphorylation. Oncotarget. 7:59388–59401. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Islam MM, Banerjee T, Packard CZ, Kotian S, Selvendiran K, Cohn DE and Parvin JD: HDAC10 as a potential therapeutic target in ovarian cancer. Gynecol Oncol. 144:613–620. 2017. View Article : Google Scholar : PubMed/NCBI

17 

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Wang X, Liu J, Zhen J, Zhang C, Wan Q, Liu G, Wei X, Zhang Y, Wang Z, Han H, et al: Histone deacetylase 4 selectively contributes to podocyte injury in diabetic nephropathy. Kidney Int. 86:712–725. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Song C, Zhu S, Wu C and Kang J: Histone deacetylase (HDAC) 10 suppresses cervical cancer metastasis through inhibition of matrix metalloproteinase (MMP) 2 and 9 expression. J Biol Chem. 288:28021–28033. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Jin Z, Jiang W, Jiao F, Guo Z, Hu H and Wang L and Wang L: Decreased expression of histone deacetylase 10 predicts poor prognosis of gastric cancer patients. Int J Clin Exp Pathol. 7:5872–5879. 2014.PubMed/NCBI

21 

Petrelli F, Tomasello G, Borgonovo K, Ghidini M, Turati L, Dallera P, Passalacqua R, Sgroi G and Barni S: Prognostic survival associated with left-sided vs right-sided colon cancer: A systematic review and meta-analysis. JAMA Oncol. Oct 27–2016.(Epub ahead of print).

22 

Bauer KM, Hummon AB and Buechler S: Right-side and left-side colon cancer follow different pathways to relapse. Mol Carcinog. 51:411–421. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

October-2017
Volume 14 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Tao X, Yan Y, Lu L and Chen B: HDAC10 expression is associated with DNA mismatch repair gene and is a predictor of good prognosis in colon carcinoma. Oncol Lett 14: 4923-4929, 2017
APA
Tao, X., Yan, Y., Lu, L., & Chen, B. (2017). HDAC10 expression is associated with DNA mismatch repair gene and is a predictor of good prognosis in colon carcinoma. Oncology Letters, 14, 4923-4929. https://doi.org/10.3892/ol.2017.6818
MLA
Tao, X., Yan, Y., Lu, L., Chen, B."HDAC10 expression is associated with DNA mismatch repair gene and is a predictor of good prognosis in colon carcinoma". Oncology Letters 14.4 (2017): 4923-4929.
Chicago
Tao, X., Yan, Y., Lu, L., Chen, B."HDAC10 expression is associated with DNA mismatch repair gene and is a predictor of good prognosis in colon carcinoma". Oncology Letters 14, no. 4 (2017): 4923-4929. https://doi.org/10.3892/ol.2017.6818