产甲胎蛋白胃癌的新临床特征和前沿科学问题

doi:10.19723/j.issn.1671-167X.2026.02.006

摘要/Abstract

摘要：

产甲胎蛋白胃癌(alpha-fetoprotein-producing gastric cancer，AFPGC)是一种特殊类型的胃癌，具有独特的生物学特性和临床表现。AFPGC大多数属于染色体不稳定型(chromosomal instability, CIN)，其基因突变特征包括TP53、MUC16突变和ERBB2、周期蛋白CCNE1等的扩增。甲胎蛋白(alpha-fetoprotein, AFP)在胃癌组织中高表达，且与肿瘤T分期和患者预后相关。部分AFPGC患者虽血清AFP水平正常，但胃癌组织中AFP表达呈阳性。组织中的AFP在肿瘤的侵袭性和免疫逃逸中起着关键作用，通过调节免疫细胞功能，可能促使肿瘤生长和转移。临床上，AFP、癌胚抗原(carcinoembryonic antigen，CEA)、人绒毛膜促性腺素(human chorionic gonadotropin，HCG)、维生素K缺乏或拮抗剂-Ⅱ诱导的蛋白质(protein induced by vitamin K absence or antagonist-Ⅱ，PIVKA-Ⅱ，又称异常凝血酶原)等标志物的联合升高提示胃癌的高恶性潜能，尤其在晚期患者中，此类患者预后较差。免疫治疗在AFPGC中的应用显示出一定潜力，但疗效仍需进一步研究验证。尽管已有个案报告，但目前尚无统一的治疗方案，个体化、多模式治疗是提高AFPGC治疗效果的关键，因此，综合评估AFP水平、影像学和病理特征对临床治疗至关重要。

关键词: 产甲胎蛋白胃癌, 突变, 肿瘤逃逸, 肿瘤生物标记

Abstract:

Alpha-fetoprotein-producing gastric cancer (AFPGC) represents a distinct clinical entity within the landscape of gastric malignancies, characterized by its aggressive biological behavior and unique clinicopathological profile. Most cases are classified under the chromosomal instability (CIN) subtype, featuring a molecular signature often marked by TP53 and MUC16 mutations, as well as significant amplifications of genes like ERBB2 and the cell cycle regulator CCNE1. As a serum tumor marker, alpha-fetoprotein (AFP) is typically highly elevated in AFPGC and correlates closely with tumor T-stage and patient prognosis. However, discordant expression is observed in some cases, characterized by positive intra-tumoral AFP expression in the presence of normal serum AFP levels. Moreover, intra-tumoral AFP plays an important role in both tumor invasiveness and immune evasion. It may promote tumor pro-liferation and metastasis by modulating immune cell activity. The high malignant potential of AFPGC may be attributable to its capacity to actively remodel the tumor milieu toward an immunosuppressive phenotype. Clinical studies have shown that the co-elevation of AFP with other markers, such as carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG), and protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ) often indicates a high malignant potential and a poor prognosis in gastric cancer, particularly in patients with advanced disease. Such concurrent detection of two or more biomar-kers facilitates the assessment of tumor aggressiveness as well as provides a clinical basis for early diagnosis and prognostic evaluation. Currently, there are no standardized guidelines for AFPGC treatment, and strategies often rely on individual pathological profile, tumor staging, and biomarker levels. In addition, immune checkpoint inhibitors (ICIs) have shown preliminary efficacy in some cases. Immunotherapy has demonstrated potential in AFPGC treatment, but the overall therapeutic outcomes and underlying mechanisms of resistance warrant further clinical validation and investigation. Individualized and multimodal therapeutic approaches are fundamental to improving clinical outcomes due to the high degree of heterogeneity in AFPGC. Therefore, a comprehensive evaluation of serum AFP levels, radiological findings, and pathological characteristics is essential for the development of personalized treatment regimens.

Key words: Alpha-fetoprotein-producing gastric cancer, Mutation, Tumor escape, Tumor biomarkers

中图分类号:

R735.2

罗必显, 刘洪铭, 谢伟勋, 龚渭华. 产甲胎蛋白胃癌的新临床特征和前沿科学问题[J]. 北京大学学报（医学版）, 2026, 58(2): 257-265.

Bixian LUO, Hongming LIU, Weixun XIE, Weihua GONG. Novel clinical insights and frontier issues in alpha- fetoprotein-producing gastric cancer[J]. Journal of Peking University (Health Sciences), 2026, 58(2): 257-265.

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Features	AFPGC	HAS	HCC
Cellular origin	Gastric glandular epithelium	Stomach (with hepatoid differentiation)	Hepatic parenchyma
AFP levels^[7]	Elevated (≥7 μg/L)	Elevated	Significantly elevated (pathognomonic)
Pathological features^[8-9]	Gastric adenocarcinoma, focal hepatoid changes	Dual features of gastric adenocarcinoma and HCC	Liver malignancy, hepatoid differentiation
Molecular profile^[10-11]	Gastric-like, TP53 (55%), CDH1	HCC-like, TP53 (66%)	TP53, CTNNB1, TERT promoter mutations
ERBB2 amplification^[11]	Highest (25.8%)	Intermediate (21.05%)	Lowest (0.6%)
Molecular/IHC markers^[12-13]	AFP (+), GPC3 (64.84%)	AFP (+), GPC3 (78.1%)	AFP (+), GPC3 (+), HCC hallmarks
Therapeutic strategies^[14]	Resection, chemo, and immunothe-rapy	Refractory to gastric cancer regimens, HCC-oriented therapy	Transplant, targeted therapy, and immunotherapy
Prognosis^[15]	Poor, AFP elevation correlated with stage and invasiveness	Poor, especially in AFP-high cases, low 5-year survival, frequent liver metastasis	Poor, particularly in advanced stages or patients with cirrhosis

Subtype	n	AFP (+)	VEGF (+)	CEA (+)
Hepatoid	19	7 (36.8%)	9 (47.4%)	7 (36.8%)
Yolk sac tumor-like	32	7 (21.9%)	9 (28.1%)	24 (75.0%)
Fetal gastrointestinal	5	0 (0)	1 (20.0%)	4 (80.0%)
Mixed	8	1 (12.5%)	2 (25.0%)	7 (87.5%)

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