HOTAIR and gastric cancer: A lesson from two meta-analyses

Vol. 59 - No. 3 PaNmiNerVa medica 201

anno: 2017 mese: September Volume: 59 No: 3

rivista: Panminerva medica cod rivista: Panminerva med

Lavoro: 3333-PaN

titolo breve: HOTair aNd GaSTric caNcer primo autore: FaGOONee

pagine: 201-2

citazione: Panminerva med 2017;59:201-2

patients with Gc.

_{The database search (period up to}

November 15, 2015) permitted to include 10 studies.

The results showed that high expression of HOTair

was significantly associated with clinicopathological

features, especially depth of tumor invasion, lymph

node metastasis, vessel invasion and TNm stage. in

ad-dition, aberrant HOTAIR expression was significantly

associated with prognosis.

_{Thus, these 2 meta-analyses}

were, in the first case, incomplete and inconclusive, and

in the second case, exhaustive leading to a clear

con-clusion. regarding the databases used, these were in

part similar (Pubmed, embase). The difference in other

databases (iSi Web of Science, Springer, chinese

Na-tional Knowledge infrastructure and WanFang digital

database) employed did not influence the result,

except

for one study published in Chinese,

_{and included by}

Liu et al.

A meta-analysis is a statistical analysis that combines

the results of multiple scientific studies.

The basic tenet behind meta-analyses is that there is a

common truth behind all conceptually similar scientific

studies, but which has been measured with a certain

er-ror within individual studies. A key benefit of this

ap-proach is the aggregation of information leading to a

higher statistical power and more robust point estimate

than is possible from the measure derived from any

in-dividual study.

_{Thus, the completeness of the sample}

size is the crucial element when designing a

anal-ysis. Unfortunately, there is a trend to perform

meta-analyses with heterogeneity on several aspects.

m

any factors affect the prognosis of gastric cancer

(Gc). invasion and metastasis are, however, the

leading causes of death and finding potential genetic

in-volvements becomes crucial. each result in this context

is, hence, of utmost importance for the scientific

com-munity.

The HOX transcript antisense rNa (HOTair) is a

human gene located on chromosome 12 and it represents

the first example of an RNA expressed on one

chromo-some that has been found to influence transcription on

another chromosome. The HOTair gene contains 6232

bp and encodes 2.2 kb long noncoding rNa molecule,

which controls gene expression. it is known that high

levels of HOTair expression in some malignancies,

as primary breast tumors, are a significant predictor of

subsequent metastasis and death.

Recently, the potential role of HOTAIR in

gastroin-testinal cancers has been investigated in two

meta-anal-yses.

_{The first, published by Miao et al., investigated}

the correlation between over-expression of HOTair

and survival of patients with solid tumors. The database

search (period June 1

_{2007-May 1}

_{2016) permitted}

to include 21 studies, with only 2 of these considering

patients with Gc.

_{due to this limited sample}

regard-ing GC, for their final considerations, the authors

ana-lyzed only studies including patients with esophageal

squamous cell carcinoma (N.=4) and colorectal cancer

(N.=4).

_{The second meta-analysis, published by Liu}

et al., investigated the association of HOTair

expres-sion with clinicopathological features and prognosis in

E D I T O R I A L

HOTair and gastric cancer:

a lesson from two meta-analyses

Sharmila FaGOONee

_{*, Marilena DURAZZO}

1_{Institute for Biostructures and Bioimages (CNR) c/o Molecular Biotechnology Center, University of Turin, Turin, Italy;} 2_{department of} Medical Sciences, University of Turin, Turin, Italy

*Corresponding author: Sharmila Fagoonee, Institute for Biostructures and Bioimages (CNR) c/o Molecular Biotechnology Center, University of Turin, Turin, Italy. E-mail: sharmila.fagoonee@unito.it

Panminerva medica 2017 September;59(3):201-2 dOi: 10.23736/S0031-0808.17.03333-X © 2017 EDIZIONI MINERVA MEDICA

FaGOONee HOTair aNd GaSTric caNcer

202 PaNmiNerVa medica September 2017

sion of gastric adenocarcinoma. Biochem Biophys Res Commun 2014;451:171-8.

9. Okugawa Y, Toiyama Y, Hur K, Toden S, Saigusa S, Tanaka K, et

al. metastasis-associated long non-coding rNa drives gastric

can-cer development and promotes peritoneal metastasis. carcinogenesis 2014;35:2731-9.

10. Liu Y, Li T, Wang X, Shi Y, Yang Y, Guo r. The expression and clini-cal significance of lncRNA HOTAIR in gastric cancer. Modern Oncol 2015;23:2649-52 [article in chinese].

11. Zhao W, Dong S, Duan B, Chen P, Shi L, Gao H, et al. HOTair is a predictive and prognostic biomarker for patients with advanced gas-tric adenocarcinoma receiving fluorouracil and platinum combination chemotherapy. Am J Transl Res 2015;7:1295-302.

12. Liu YW, Sun M, Xia R, Zhang EB, Liu XH, Zhang ZH, et al. Lin-cHOTAIR epigenetically silences miR34a by binding to PRC2 to promote the epithelial-to-mesenchymal transition in human gastric cancer. cell death dis 2015;6:e1802.

13. Liu XH, Sun M, Nie FQ, Ge YB, Zhang EB, Yin DD, et al. Lnc rNa HOTair functions as a competing endogenous rNa to regu-late HER2 expression by sponging miR-331-3p in gastric cancer. Mol cancer 2014;13:92.

14. Zhang ZZ, Shen ZY, Shen YY, Zhao EH, Wang M, Wang CJ, et al. HOTair long noncoding rNa promotes gastric cancer metastasis through suppression of Poly r(C)-Binding Protein (PCBP) 1. Mol cancer Ther 2015;14:1162-70.

15. Haidich AB. Meta-analysis in medical research. Hippokratia 2010;14(Suppl 1):29-37.

16. Song W, Zhang RJ, Zou SB. Long noncoding RNA MALAT1 as a po-tential novel biomarker in digestive system cancers: a meta-analysis. minerva med 2016;107:245-50.

17. Chen T, Yang P, He ZY. Long non-coding RNA H19 can predict a poor prognosis and lymph node metastasis: a meta-analysis in human cancer. minerva med 2016;107:251-8.

18. Liu FT, Zhu PQ, Luo HL, Zhang Y, Qiu C. Prognostic value of long non-coding RNA UCA1 in human solid tumors. Oncotarget 2016;7:5799-8000.

19. Liu FT, Xue QZ, Zhu ZM, Qiu C, Hao TF, Zhu PQ, et al. Long non-coding RNA PVT1, a novel promising biomarker to predict lymph node metastasis and prognosis: a meta-analysis. Panminerva Med 2016;58:160-6.

20. connell Lc, mota Jm, Braghiroli mi, Hoff Pm. The rising incidence of younger patients with colorectal cancer: questions about screening, biology, and treatment. Curr Treat Options Oncol 2017;18:23. 21. Pellicano r, ribaldone dG, Fagoonee S, astegiano m, Saracco G,

mégraud F. a 2016 panorama of Helicobacter pylori infection: key messages for clinicians. Panminerva med 2016;58:304-17.

Some examples include the propensity to correlate

the expression of some long noncoding rNa molecules

either with survival, in patients with cancers of

differ-ent digestive tracts,

_{or with poor prognosis and lymph}

node metastasis, in human cancers grouped as arising or

not in the digestive system.

In conclusion, it is better to avoid meta-analyses with

patients suffering from cancers of different organs,

con-sidering the fact that different pathogenesis affects these

different cancers.

References

1. Fagoonee S, Singh Sr, altruda F, Pellicano r. Surface markers of gastric cancer stem cells. minerva Biotecnol 2015;27:225-33. 2. Lv Z, Xu Q, Yuan Y. A systematic review and meta-analysis of the

as-sociation between long non-coding RNA polymorphisms and cancer risk. mutation res 2017;771:1-14.

3. Miao Z, Ding J, Chen B, Yang Y, Chen Y. HOTAIR overexpression correlated with worse survival in patients with solid tumors. minerva med 2016;107:392-400.

4. Liu FT, Qiu C, Luo HL, Zhang Y, Xia GF, Hao TF, et al. The asso-ciation of HOTair expression with clinicopathological features and prognosis in gastric cancer patients. Panminerva med 2016;58:167-74.

5. Xu ZY, Yu QM, Du YA, Yang LT, Dong RZ, Huang L, et al. Knock-down of long non-coding rNa HOTair suppresses tumor invasion and reverses epithelial-mesenchymal transition in gastric cancer. Int J Biol Sci 2013;9:587-97.

6. ma G, Wang Q, Lv c, Qiang F, Hua Q, chu H, et al. The prog-nostic significance of HOTAIR for predicting clinical outcome in patients with digestive system tumors. J Cancer Res Clin Oncol 2015;141:2139-45.

7. Endo H, Shiroki T, Nakagawa T, Yokoyama M, Tamai K, Yamanami H, et al. enhanced expression of long non-coding rNa HOTair is associated with the development of gastric cancer. PLoS One 2013;8:e77070.

8. Lee NK, Lee JH, Park cH, Yu d, Lee Yc, cheong JH, et al. Long non-coding rNa HOTair promotes carcinogenesis and

inva-Conflicts of interest.—The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.

Article first published online: May 8, 2017.

(Cite this article as: Fagoonee S, Durazzo M. HOTAIR and gastric cancer: a lesson from two meta-analyses. Panminerva Med 2017;59:201-2. DOI: 10.23736/ S0031-0808.17.03333-X)