TY - JOUR
T1 - Expression of cancer testis antigens in tumor-adjacent normal liver is associated with post-resection recurrence of hepatocellular carcinoma
AU - Noordam, Lisanne
AU - Ge, Zhouhong
AU - Özturk, Hadiye
AU - Doukas, Michail
AU - Mancham, Shanta
AU - Boor, Patrick P.C.
AU - Carrascosa, Lucia Campos
AU - Zhou, Guoying
AU - van den Bosch, Thierry P.P.
AU - Pan, Qiuwei
AU - Ijzermans, Jan N.M.
AU - Bruno, Marco J.
AU - Sprengers, Dave
AU - Kwekkeboom, Jaap
N1 - Funding Information:
Funding: This study was supported by the Erasmus MC grant 2014 awarded to J. Kwekkeboom by the Erasmus Medical Center, Rotterdam.
Funding Information:
This study was supported by the Erasmus MC grant 2014 awarded to J. Kwekkeboom by the Erasmus Medical Center, Rotterdam.RNA from testicular tissues was kindly provided to us by L.H.J. Looijenga and FFPE blocks of testis tissues by R Hersmus (Department of Pathology, Erasmus MC). RNA from healthy bone marrow was provided to us by E. Braakman (Department of Hematology, Erasmus MC), and healthy donor kidney by Carla Baan (Department of Internal Medicine, both from Erasmus MC). Anti-MAGEA9 mAb was kindly provided by Y. Fradet, Laboratoire d?Uro-Oncoloie Exp?rimentale, Universit? Laval, Qu?bec, Canada. We would like to thank Kees Melief (ISA Pharmaceuticals, Leiden) for carefully reviewing our manuscript and Nicole S. Erler (Department of Epidemiology and Biostatistcis, Erasmus MC) for statistical advice.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/5/20
Y1 - 2021/5/20
N2 - High recurrence rates after resection of hepatocellular carcinoma (HCC) with curative intent impair clinical outcomes of HCC. Cancer/testis antigens (CTAs) are suitable targets for cancer immunotherapy if selectively expressed in tumor cells. The aims were to identify CTAs that are frequently and selectively expressed in HCC-tumors, and to investigate whether CTAs could serve as biomarkers for occult metastasis. Tumor and paired tumor-free liver (TFL) tissues of HCC-patients and healthy tissues were assessed for mRNA expression of 49 CTAs by RT-qPCR and protein expression of five CTAs by immunohistochemistry. Twelve CTA-mRNAs were expressed in ≥10% of HCC-tumors and not in healthy tissues except testis. In tumors, mRNA and protein of ≥ 1 CTA was expressed in 78% and 71% of HCC-patients, respectively. In TFL, CTA mRNA and protein was found in 45% and 30% of HCC-patients, respectively. Interestingly, CTA-expression in TFL was an independent negative prognostic factor for post-resection HCC-recurrence and survival. We established a panel of 12 testis-restricted CTAs expressed in tumors of most HCC-patients. The increased risk of HCC-recurrence in patients with CTA expression in TFL, suggests that CTA-expressing (pre-)malignant cells may be a source of HCC-recurrence, reflecting the relevance of targeting these to prevent HCC-recurrence.
AB - High recurrence rates after resection of hepatocellular carcinoma (HCC) with curative intent impair clinical outcomes of HCC. Cancer/testis antigens (CTAs) are suitable targets for cancer immunotherapy if selectively expressed in tumor cells. The aims were to identify CTAs that are frequently and selectively expressed in HCC-tumors, and to investigate whether CTAs could serve as biomarkers for occult metastasis. Tumor and paired tumor-free liver (TFL) tissues of HCC-patients and healthy tissues were assessed for mRNA expression of 49 CTAs by RT-qPCR and protein expression of five CTAs by immunohistochemistry. Twelve CTA-mRNAs were expressed in ≥10% of HCC-tumors and not in healthy tissues except testis. In tumors, mRNA and protein of ≥ 1 CTA was expressed in 78% and 71% of HCC-patients, respectively. In TFL, CTA mRNA and protein was found in 45% and 30% of HCC-patients, respectively. Interestingly, CTA-expression in TFL was an independent negative prognostic factor for post-resection HCC-recurrence and survival. We established a panel of 12 testis-restricted CTAs expressed in tumors of most HCC-patients. The increased risk of HCC-recurrence in patients with CTA expression in TFL, suggests that CTA-expressing (pre-)malignant cells may be a source of HCC-recurrence, reflecting the relevance of targeting these to prevent HCC-recurrence.
UR - http://www.scopus.com/inward/record.url?scp=85106194886&partnerID=8YFLogxK
U2 - 10.3390/cancers13102499
DO - 10.3390/cancers13102499
M3 - Article
AN - SCOPUS:85106194886
VL - 13
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 10
M1 - 2499
ER -
