Tumor Biology

, Volume 36, Issue 10, pp 7675–7683 | Cite as

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

  • Ying-En Lee
  • Hong-Lin He
  • Yow-Ling Shiue
  • Sung-Wei Lee
  • Li-Ching Lin
  • Ting-Feng Wu
  • I-Wei Chang
  • Hao-Hsien Lee
  • Chien-Feng LiEmail author
Research Article


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.


HSD17B2 HMGCS2 Rectal cancer Chemoradiotherapy CCRT 



Concurrent chemoradiotherapy


17β-hydroxysteroid dehydrogenase type 2






3-hydroxy-3-methylglutaryl-CoA synthase


Endoscopic ultrasound






American Joint Committee on Cancer


Tumor regression grade


Disease-free survival


Local recurrence-free survival


Metastasis-free survival


Estrogen receptor beta



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


Supplementary material

13277_2015_3503_Fig4_ESM.gif (155 kb)
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)

13277_2015_3503_MOESM1_ESM.tif (2.5 mb)
High resolution image (TIFF 2576 kb)
13277_2015_3503_MOESM2_ESM.doc (88 kb)
Table S1 (DOC 87 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Ying-En Lee
    • 1
  • Hong-Lin He
    • 2
    • 3
  • Yow-Ling Shiue
    • 3
  • Sung-Wei Lee
    • 4
  • Li-Ching Lin
    • 4
  • Ting-Feng Wu
    • 5
  • I-Wei Chang
    • 2
  • Hao-Hsien Lee
    • 6
  • Chien-Feng Li
    • 5
    • 7
    • 8
    • 9
    Email author
  1. 1.Department of AnesthesiologyKaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineKaohsiungTaiwan
  2. 2.Department of Pathology, E-DA HospitalI-Shou UniversityKaohsiungTaiwan
  3. 3.Institute of Biomedical ScienceNational Sun Yat-sen UniversityKaohsiungTaiwan
  4. 4.Department of Radiation OncologyChi Mei Medical CenterLiouyingTaiwan
  5. 5.Department of BiotechnologySouthern Taiwan University of Science and TechnologyTainanTaiwan
  6. 6.Department of SurgeryChi Mei Medical CenterLiouyingTaiwan
  7. 7.Graduate Institute of Clinical Medicine, College of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
  8. 8.National Institute of Cancer ResearchNational Health Research InstitutesTainanTaiwan
  9. 9.Department of PathologyChi Mei Medical CenterTainanTaiwan

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