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The prognostic impact of lipid biosynthesis-associated markers, HSD17B2 and HMGCS2, in rectal cancer treated with neoadjuvant concurrent chemoradiotherapy

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Tumor Biology

Abstract

Neoadjuvant concurrent chemoradiotherapy has been widely used for rectal cancer to improve local tumor control. The varied response of individual tumors encouraged us to search for useful biomarkers to predict the therapeutic response. The study was aimed to evaluate the prognostic impact of lipid biosynthesis-associated biomarkers in rectal cancer patients treated with preoperative chemoradiotherapy. Through analysis of the previously published gene expression profiling database focusing on genes associated with lipid biosynthesis, we found that HSD17B2 and HMGCS2 were the top two significantly upregulated genes in the non-responders. We further evaluated their expression by immunohistochemistry in the pre-treatment tumor specimens from 172 patients with rectal cancer and statistically analyzed the associations between their expression and various clinicopathological factors, as well as survival. High expression of HMGCS2 or HSD17B2 was significantly associated with advanced pre- and post-treatment tumor or nodal status (P < 0.001) and lower tumor regression grade (P < 0.001). More importantly, high expression of either HMGCS2 or HSD17B2 was of prognostic significance, with HMGCS2 overexpression indicating poor prognosis for disease-free survival (P = 0.0003), local recurrence-free survival (P = 0.0115), and metastasis-free survival (P = 0.0119), while HSD17B2 overexpression was associated with poor prognosis for disease-free survival (P <0.0001), local recurrence-free survival (P = 0.0009), and metastasis-free survival (P < 0.0001). In multivariate analysis, only HSD17B2 overexpression remained as an independent prognosticator for shorter disease-free survival (P < 0.001) and metastasis-free survival (P = 0.008). In conclusion, high expression of either HSD17B2 or HMGCS2 predicted poor susceptibility of rectal cancer to preoperative chemoradiotherapy. Both acted as promising prognostic factors, particularly HSD17B2.

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Abbreviations

CCRT:

Concurrent chemoradiotherapy

HSD17B2:

17β-hydroxysteroid dehydrogenase type 2

E2:

Estradiol

E1:

Estrone

HMGCS2:

3-hydroxy-3-methylglutaryl-CoA synthase

EUS:

Endoscopic ultrasound

Pre-Tx:

Pretreatment

Post-Tx:

Posttreatment

AJCC:

American Joint Committee on Cancer

TRG:

Tumor regression grade

DFS:

Disease-free survival

LRFS:

Local recurrence-free survival

MeFS:

Metastasis-free survival

ERß:

Estrogen receptor beta

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Acknowledgments

This study is supported by the Chi Mei Medical Center (CMFHR10303), Ministry of Health and Welfare (Health and welfare surcharge of tobacco products, MOHW104-TDU-B-212-124-003), and E-Da Hospital (EDAHP104022). The authors are grateful to the BioBank of Chi Mei Medical Center for providing the tumor samples.

Conflicts of interest

None

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Author notes

    Authors and Affiliations

    1. Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

      Ying-En Lee

    2. Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan

      Hong-Lin He & I-Wei Chang

    3. Institute of Biomedical Science, National Sun Yat-sen University, Kaohsiung, Taiwan

      Hong-Lin He & Yow-Ling Shiue

    4. Department of Radiation Oncology, Chi Mei Medical Center, Liouying, Tainan, Taiwan

      Sung-Wei Lee & Li-Ching Lin

    5. Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan

      Ting-Feng Wu & Chien-Feng Li

    6. Department of Surgery, Chi Mei Medical Center, Liouying, Tainan, Taiwan

      Hao-Hsien Lee

    7. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

      Chien-Feng Li

    8. National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan

      Chien-Feng Li

    9. Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan

      Chien-Feng Li

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    1. Ying-En Lee
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    Correspondence to Chien-Feng Li.

    Additional information

    Ying-En Lee and Hong-Lin He contributed equally to this work.

    Hao-Hsien Lee and Chien-Feng Li contributed equally as senior of this work.

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    Figure S1

    Survival analysis plotted by using Kaplan-Meier methods. When categorizing the expression of HSD17B2 or HMGCS2 into three groups, namely low, medium, and high expression. Either high expression of HSD17B2 or HMGCS2 remained significantly predictive for inferior disease-free (A, D), local recurrence-free (B, E), and metastasis-free survival (C, F, respectively). (GIF 155 kb)

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    Table S1

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    Lee, YE., He, HL., Shiue, YL. et al. The prognostic impact of lipid biosynthesis-associated markers, HSD17B2 and HMGCS2, in rectal cancer treated with neoadjuvant concurrent chemoradiotherapy. Tumor Biol. 36, 7675–7683 (2015). https://doi.org/10.1007/s13277-015-3503-2

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    • DOI: https://doi.org/10.1007/s13277-015-3503-2

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