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

9 Citations (Scopus)

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

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Small Untranslated RNA
Esophageal Neoplasms
Recurrence
MicroRNAs
Histone Deacetylase Inhibitors
Survival
Sirolimus
Patient Care
Phosphotransferases
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)
  • Gastroenterology

Cite this

Jang, H. J., Lee, H. S., Burt, B. M., Lee, G. K., Yoon, K. A., Park, Y. Y., ... 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

Integrated genomic analysis of recurrence-associated small non-coding RNAs in oesophageal cancer. / Jang, Hee Jin; Lee, Hyun Sung; Burt, Bryan M.; Lee, Geon Kook; Yoon, Kyong Ah; Park, Yun Yong; Sohn, Bo Hwa; Kim, Sang Bae; Kim, Moon Soo; Lee, Jong Mog; Joo, Jungnam; Kim, Sang Cheol; Yun, Ju Sik; Na, Kook Joo; Choi, Yoon La; Park, Jong Lyul; Kim, Seon Young; Lee, Yong Sun; Han, Leng; Liang, Han; Mak, Duncan; Burks, Jared K.; Zo, Jae Ill; Sugarbaker, David J.; Shim, Young Mog; Lee, Ju Seog.

In: Gut, 09.08.2016.

Research output: Contribution to journalArticle

Jang, HJ, Lee, HS, Burt, BM, Lee, GK, Yoon, KA, Park, YY, Sohn, BH, Kim, SB, Kim, MS, Lee, JM, Joo, J, Kim, SC, Yun, JS, Na, KJ, Choi, YL, Park, JL, Kim, SY, Lee, YS, Han, L, Liang, H, Mak, D, Burks, JK, Zo, JI, Sugarbaker, DJ, Shim, YM & Lee, JS 2016, 'Integrated genomic analysis of recurrence-associated small non-coding RNAs in oesophageal cancer', Gut. https://doi.org/10.1136/gutjnl-2015-311238
Jang, Hee Jin ; Lee, Hyun Sung ; Burt, Bryan M. ; Lee, Geon Kook ; Yoon, Kyong Ah ; Park, Yun Yong ; Sohn, Bo Hwa ; Kim, Sang Bae ; Kim, Moon Soo ; Lee, Jong Mog ; Joo, Jungnam ; Kim, Sang Cheol ; Yun, Ju Sik ; Na, Kook Joo ; Choi, Yoon La ; Park, Jong Lyul ; Kim, Seon Young ; Lee, Yong Sun ; Han, Leng ; Liang, Han ; Mak, Duncan ; Burks, Jared K. ; Zo, Jae Ill ; Sugarbaker, David J. ; Shim, Young Mog ; Lee, Ju Seog. / Integrated genomic analysis of recurrence-associated small non-coding RNAs in oesophageal cancer. In: Gut. 2016.
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title = "Integrated genomic analysis of recurrence-associated small non-coding RNAs in oesophageal cancer",
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.",
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T1 - Integrated genomic analysis of recurrence-associated small non-coding RNAs in oesophageal cancer

AU - Jang, Hee Jin

AU - Lee, Hyun Sung

AU - Burt, Bryan M.

AU - Lee, Geon Kook

AU - Yoon, Kyong Ah

AU - Park, Yun Yong

AU - Sohn, Bo Hwa

AU - Kim, Sang Bae

AU - Kim, Moon Soo

AU - Lee, Jong Mog

AU - Joo, Jungnam

AU - Kim, Sang Cheol

AU - Yun, Ju Sik

AU - Na, Kook Joo

AU - Choi, Yoon La

AU - Park, Jong Lyul

AU - Kim, Seon Young

AU - Lee, Yong Sun

AU - Han, Leng

AU - Liang, Han

AU - Mak, Duncan

AU - Burks, Jared K.

AU - Zo, Jae Ill

AU - Sugarbaker, David J.

AU - Shim, Young Mog

AU - Lee, Ju Seog

PY - 2016/8/9

Y1 - 2016/8/9

N2 - 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.

AB - 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.

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