Integrated genomic analysis of recurrence-associated small non-coding RNAs in oesophageal cancer

Hee Jin Jang, Hyun Sung Lee, Bryan M. Burt, Geon Kook Lee, Kyong Ah Yoon, Yun Yong Park, Bo Hwa Sohn, Sang Bae Kim, Moon Soo Kim, Jong Mog Lee, Jungnam Joo, Sang Cheol Kim, Ju Sik Yun, Kook Joo Na, Yoon La Choi, Jong Lyul Park, Seon Young Kim, Yong Sun Lee, Leng Han, Han LiangDuncan Mak, Jared K. Burks, Jae Ill Zo, David J. Sugarbaker, Young Mog Shim, Ju Seog Lee

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Objective Oesophageal squamous cell carcinoma (ESCC) is a heterogeneous disease with variable outcomes that are challenging to predict. A better understanding of the biology of ESCC recurrence is needed to improve patient care. Our goal was to identify small non-coding RNAs (sncRNAs) that could predict the likelihood of recurrence after surgical resection and to uncover potential molecular mechanisms that dictate clinical heterogeneity. Design We developed a robust prediction model for recurrence based on the analysis of the expression profile data of sncRNAs from 108 fresh frozen ESCC specimens as a discovery set and assessment of the associations between sncRNAs and recurrence-free survival (RFS). We also evaluated the mechanistic and therapeutic implications of sncRNA obtained through integrated analysis from multiple datasets. Results We developed a risk assessment score (RAS) for recurrence with three sncRNAs (microRNA (miR)-223, miR-1269a and nc886) whose expression was significantly associated with RFS in the discovery cohort (n=108). RAS was validated in an independent cohort of 512 patients. In multivariable analysis, RAS was an independent predictor of recurrence (HR, 2.27; 95% CI, 1.26 to 4.09; p=0.007). This signature implies the expression of ?Np63 and multiple alterations of driver genes like PIK3CA. We suggested therapeutic potentials of immune checkpoint inhibitors in low-risk patients, and Polo-like kinase inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and histone deacetylase inhibitors in high-risk patients. Conclusion We developed an easy-to-use prognostic model with three sncRNAs as robust prognostic markers for postoperative recurrence of ESCC. We anticipate that such a stratified and systematic, tumour-specific biological approach will potentially contribute to significant improvement in ESCC treatment.

Original languageEnglish (US)
JournalGut
DOIs
StateAccepted/In press - Aug 9 2016

ASJC Scopus subject areas

  • Medicine(all)
  • Gastroenterology

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    Jang, H. J., Lee, H. S., Burt, B. M., Lee, G. K., Yoon, K. A., Park, Y. Y., Sohn, B. H., Kim, S. B., Kim, M. S., Lee, J. M., Joo, J., Kim, S. C., Yun, J. S., Na, K. J., Choi, Y. L., Park, J. L., Kim, S. Y., Lee, Y. S., Han, L., ... Lee, J. S. (Accepted/In press). Integrated genomic analysis of recurrence-associated small non-coding RNAs in oesophageal cancer. Gut. https://doi.org/10.1136/gutjnl-2015-311238