Noordam Lisanne, Ge Zhouhong, Özturk Hadiye, Doukas Michail, Mancham Shanta, Boor Patrick P C, Campos Carrascosa Lucia, Zhou Guoying, van den Bosch Thierry P P, Pan Qiuwei, IJzermans Jan N M, Bruno Marco J, Sprengers Dave, Kwekkeboom Jaap
Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, 3000 CA Rotterdam, The Netherlands.
Department of Pathology, Erasmus MC-University Medical Center, 3000 CA Rotterdam, The Netherlands.
Cancers (Basel). 2021 May 20;13(10):2499. doi: 10.3390/cancers13102499.
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.
以治愈为目的切除肝细胞癌（HCC）后高复发率会损害HCC的临床治疗效果。癌症/睾丸抗原（CTA）如果在肿瘤细胞中选择性表达，则是癌症免疫治疗的合适靶点。本研究旨在鉴定在HCC肿瘤中频繁且选择性表达的CTA，并研究CTA是否可作为隐匿性转移的生物标志物。通过逆转录定量聚合酶链反应（RT-qPCR）评估HCC患者的肿瘤组织、配对的癌旁肝组织（TFL）以及健康组织中49种CTA的mRNA表达情况，并通过免疫组织化学评估5种CTA的蛋白表达情况。12种CTA的mRNA在≥10%的HCC肿瘤中表达，除睾丸外，在健康组织中不表达。在肿瘤中，分别有78%和71%的HCC患者表达≥1种CTA的mRNA和蛋白。在TFL中，分别有45%和30%的HCC患者检测到CTA mRNA和蛋白。有趣的是，TFL中CTA的表达是HCC切除术后复发和生存的独立负性预后因素。我们建立了一个由12种睾丸限制性CTA组成的检测组，这些CTA在大多数HCC患者的肿瘤中表达。TFL中表达CTA的患者HCC复发风险增加，这表明表达CTA的（癌前）恶性细胞可能是HCC复发的来源，这反映了靶向这些细胞以预防HCC复发的相关性。
