Cancer Res Treat.  2019 Oct;51(4):1411-1419. 10.4143/crt.2018.663.

The Use of CD44 Variant 9 and Ki-67 Combination Can Predicts Prognosis Better Than Their Single Use in Early Gastric Cancer

Affiliations
  • 1Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, Korea.
  • 2Department of Pathology, Institute of Health Sciences, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea.
  • 3Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea. lwshmo@hanmail.net
  • 4Department of Surgery, Institute of Health Sciences, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, Korea.
  • 5Department of Surgery, Institute of Health Sciences, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea.

Abstract

PURPOSE
We previously demonstrated that CD44v9 and Ki-67 played an important role in predicting poor prognosis of early gastric cancer (EGC). However, little is known about combined use of both biomarkers as prognostic biomarker. The present study was performed to investigate the significance of CD44v9 and Ki-67 expression as a combination biomarker for EGC.
MATERIALS AND METHODS
With tissue microarray for 158 EGC tissues, we performed immunohistochemical staining for CD44v9 and Ki-67. The whole patients were divided into three groups (group A, CD44v9-negative/Ki-67-low; group B, neither group A or C; and group C, CD44v9-positive/Ki-67-high). Its clinical significance was re-analyzed with adjustment via propensity score matching (PSM). For validation, we performed bootstrap resampling.
RESULTS
The median follow-up duration was 90.4 months (range, 3.7 to 120.4 months). In the comparison according to CD44v9/Ki-67 expression, the combined use of the two biomarker clearly separated the three groups by 5-year survival rates (5-YSR, 96.3%, 89.8%, and 76.8% in group A, B, and C, respectively; p=0.009). After PSM, 5-YSR were 97.7% and 76.8% in group A+B and group C, respectively (p=0.002). Multivariable analysis demonstrated that group C had independently poor prognosis (hazard ratio, 9.137; 95% confidence interval, 1.187 to 70.366; p=0.034) compared with group A. Bootstrap resampling internally validated this result (p=0.016).
CONCLUSION
This study suggests that both positive CD44v9 and high Ki-67 expression are associated with poor prognosis in EGC, and the combined use of these markers provides better prognostic stratification than the single use of them.

Keyword

CD44v9 antigen; Ki-67 antigen; Stomach neoplasm; Prognosis

MeSH Terms

Biomarkers
Follow-Up Studies
Humans
Ki-67 Antigen
Prognosis*
Propensity Score
Stomach Neoplasms*
Survival Rate
Biomarkers
Ki-67 Antigen

Figure

  • Fig. 1. Kaplan-Meier curves for overall survival according to CD44v9 and Ki-67 expression in early gastric cancer (EGC) patients. (A) Total. (B) Well-differentiated (W/D). (C) Moderately-differentiated (M/D). (D) Poorly-differentiated (P/D) and others. (E) Intestinal type. (F) Diffuse/mixed type. Others indicate undifferentiated and mucinous adenocarcinoma, and signet ring cell carcinoma.

  • Fig. 2. Kaplan-Meier curves for overall survival according to CD44v9 and Ki-67 expression in early gastric cancer after propensity score matching.

  • Fig. 3. Kaplan-Meier curves for overall survival according to CD44v9 and Ki-67 expression in advanced gastric cancer (AGC) patients. (A) Total. (B) Well-differentiated (W/D). (C) Moderately-differentiated (M/D). (D) Poorly-differentiated (P/D) and others. (E) Intestinal type. (F) Diffuse/mixed type. Others indicate undifferentiated and mucinous adenocarcinoma, and signet ring cell carcinoma.


Reference

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