Advertisement

Tumor Biology

, Volume 37, Issue 6, pp 7327–7332 | Cite as

The prediction of survival of patients with gastric cancer with PD-L1 expression using contrast-enhanced ultrasonography

  • Lin-Ang Wang
  • Xi Wei
  • Qing Li
  • Lin Chen
Original Article

Abstract

Gastric cancer is the one of the most common cancers around the world. The prognosis of gastric cancer remains poor, due to the biological characteristics of the primary tumor as well as the recurrence after treatment. Accumulating evidence suggests the implication of programmed death ligand-1 (PD-L1) in the pathogenesis and prognosis of cancer. This study aimed to explore the CEUS as a valuable tool to improve the assessment of the therapeutic effect of the PD-L1 blocker in the treatment of gastric cancer. A total number of 105 patients with gastric cancer were enrolled in this study from June 2008 to December 2011 in our hospital. The association of PD-L1 expression level (105 cases) and CEUS parameters (100 cases) with the prognosis of gastric cancer was examined. The results showed that PD-L1-positive staining was associated with the depth of invasion, differentiation, and poor prognosis of patients with gastric cancer. The CEUS intensity (positive) exhibited poor prognosis compared to the negative counterpart. Moreover, PD-L1 and CEUS co-positivity was significantly related to a poor prognosis. The characteristic of ultrasonography images correlated with the expression of PD-L1 (r = 0.46, P = 0.0003). Collectively, the mean intensity of contrast-enhanced ultrasonography is a useful predictor in the PD-L1 expression in gastric cancer. The ultrasonography and CEUS parameter could be considered as the predictor of response to PD-L1 blocker treatment in the clinical practice.

Keywords

PD-L1 CEUS Overall survival Gastric cancer 

Notes

Acknowledgments

This work was supported by grants from the National Natural Science Foundations of China (No. 81171904 and 81401412). We thank all the people and patients who participated in this study.

References

  1. 1.
    Albiges L, Fay AP, Xie W, Krajewski K, McDermott DF, Heng DY, et al. Efficacy of targeted therapies after pd-1/pd-l1 blockade in metastatic renal cell carcinoma. Eur J Cancer (Oxford, England : 1990). 2015.Google Scholar
  2. 2.
    Hohenberger P, Gretschel S. Gastric cancer. Lancet (London, England). 2003;362:305–15.CrossRefGoogle Scholar
  3. 3.
    Matsueda S, Graham DY. Immunotherapy in gastric cancer. World J Gastroenterol WJG. 2014;20:1657–66.CrossRefPubMedGoogle Scholar
  4. 4.
    Bellmunt J, Mullane SA, Werner L, Fay AP, Callea M, Leow JJ, et al. Association of pd-l1 expression on tumor-infiltrating mononuclear cells and overall survival in patients with urothelial carcinoma. Ann Oncol Off J Eur Soc for Med Oncol ESMO. 2015;26:812–7.CrossRefGoogle Scholar
  5. 5.
    Qing Y, Li Q, Ren T, Xia W, Peng Y, Liu GL, et al. Upregulation of pd-l1 and ape1 is associated with tumorigenesis and poor prognosis of gastric cancer. Drug Des Dev Ther. 2015;9:901–9.CrossRefGoogle Scholar
  6. 6.
    Lee MH, Choi D, Park MJ, Lee MW. Gastric cancer: imaging and staging with mdct based on the 7th ajcc guidelines. Abdom Imaging. 2012;37:531–40.CrossRefPubMedGoogle Scholar
  7. 7.
    Brenner DJ, Doll R, Goodhead DT, Hall EJ, Land CE, Little JB, et al. Cancer risks attributable to low doses of ionizing radiation: assessing what we really know. Proc Natl Acad Sci U S A. 2003;100:13761–6.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Piscaglia F, Corradi F, Mancini M, Giangregorio F, Tamberi S, Ugolini G, et al. Real time contrast enhanced ultrasonography in detection of liver metastases from gastrointestinal cancer. BMC Cancer. 2007;7:171.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Cantisani V, Rubini A, Miniagio G. Ceus and strain elastography in gastric carcinoma. J Ultrasound. 2013;16:123–5.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Kwee RM, Kwee TC. Imaging in assessing lymph node status in gastric cancer. Gastric Cancer Off J Int Gastric Cancer Assoc Jpn Gastric Cancer Assoc. 2009;12:6–22.Google Scholar
  11. 11.
    Wei X, Li Y, Zhang S, Xin XJ, Zhu L, Gao M. The role of contrast-enhanced ultrasound (ceus) in the early assessment of microvascularization in patients with aggressive b-cell lymphoma treated by rituximab-chop: a preliminary study. Clin Hemorheol Microcirc. 2014;58:363–76.PubMedGoogle Scholar
  12. 12.
    Wei X, Li Y, Zhang S, Li X, Wang H, Yong X, et al. Evaluation of microvascularization in focal salivary gland lesions by contrast-enhanced ultrasonography (ceus) and color doppler sonography. Clin Hemorheol Microcirc. 2013;54:259–71.PubMedGoogle Scholar
  13. 13.
    Li Y, Wei X, Zhang S, Zhang J. Prognosis of invasive breast cancer after adjuvant therapy evaluated with vegf microvessel density and microvascular imaging. Tumour Biology J Int Soc Oncodevelopmental Biol Med. 2015.Google Scholar
  14. 14.
    Wei X, Li Y, Zhang S, Gao M. Prediction of thyroid extracapsular extension with cervical lymph node metastases (ece-ln) by ceus and braf expression in papillary thyroid carcinoma. Tumour Biol J Int Soc Oncodevelopmental Biol Med. 2014;35:8559–64.CrossRefGoogle Scholar
  15. 15.
    Wei X, Li Y, Zhang S, Ming G. Evaluation of thyroid cancer in chinese females with breast cancer by vascular endothelial growth factor (vegf), microvessel density, and contrast-enhanced ultrasound (ceus). Tumour Biol J Int Soc Oncodevelopmental Biol Med. 2014;35:6521–9.CrossRefGoogle Scholar
  16. 16.
    Krupka C, Kufer P, Kischel R, Zugmaier G, Lichtenegger FS, Kohnke T, et al. Blockade of the pd-1/pd-l1 axis augments lysis of aml cells by the cd33/cd3 bite antibody construct amg 330: Reversing a t-cell-induced immune escape mechanism. Leukemia. 2015.Google Scholar
  17. 17.
    Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-pd-1 antibody in cancer. N Engl J Med. 2012;366:2443–54.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Tang W, Chen Y, Chen S, Sun B, Gu H, Kang M. Programmed death-1 (pd-1) polymorphism is associated with gastric cardia adenocarcinoma. Int J Clin Exp Med. 2015;8:8086–93.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Eto S, Yoshikawa K, Nishi M, Higashijima J, Tokunaga T, Nakao T, et al. Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection. Gastric Cancer Off J Int Gastric Cancer Asso Jpn Gastric Cancer Asso. 2015.Google Scholar
  20. 20.
    Zheng Z, Bu Z, Liu X, Zhang L, Li Z, Wu A, et al. Level of circulating pd-l1 expression in patients with advanced gastric cancer and its clinical implications. Chin J Cancer Res Chung-kuo yen cheng yen chiu. 2014;26:104–11.PubMedGoogle Scholar
  21. 21.
    Suk KT, Lim DW, Kim MY, Park DH, Kim KH, Kim JM, et al. Thickening of the gastric wall on transabdominal sonography: a sign of gastric cancer. J ClinUltrasound JCU. 2008;36:462–6.CrossRefPubMedGoogle Scholar
  22. 22.
    Lang SA, Moser C, Gehmert S, Pfister K, Hackl C, Schnitzbauer AA, et al. Contrast-enhanced ultrasound (ceus) detects effects of vascular disrupting therapy in an experimental model of gastric cancer. Clin Hemorheol Microcirc. 2014;56:287–99.PubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping HospitalThird Military Medical UniversityChongqingChina
  2. 2.Cancer Center, Daping Hospital and Research Institute of SurgeryThird Military Medical UniversityChongqingChina
  3. 3.Department of Diagnostic and Therapeutic UltrasonographyTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and TherapyTianjinChina

Personalised recommendations