Objective: To clarify the clinicopathological, especially molecular, features of early-onset gastric cancer with the aim of informing analysis of treatment strategies. Methods: In this retrospective case-control study, we examined data from a dedicated gastric cancer database in Zhongshan Hospital affiliated to Fudan University. The original cohort comprised 2506 patients with gastric cancer who had undergone gastrectomy in Zhongshan Hospital Fudan University from July 2020 to October 2021, including 198 with early-onset gastric cancer (aged ≤45 years) and 2,308 with non-early gastric cancer. We used a simple random sampling method to select 396 of the 2,308 patients aged >45 years (ratio of 1:2) as the control group and then compared molecular diagnostic data and clinicopathological features of the two groups. Results: The median age was 39 years in the early-onset gastric cancer group, while 66 years in the control group. The clinicopathological features of early-onset gastric cancer included female predominance (59.1% [117/198] vs. 27.8% [110/396], χ2=54.816, P<0.001), less comorbidity (32.3% [64/198] vs. 57.1% [226/396], χ2=32.355, P<0.001), poorer differentiation (93.9% [186/198] vs. 74.5% [295/396], χ2=30.777, P<0.001) and higher proportion of diffuse type (40.4% [80/198] vs. 15.9% [63/396], χ2=69.639, P<0.001), distant metastasis (7.1% [14/198] vs. 2.8% [11/396], χ2=6.034, P=0.014). Regarding treatment, distal gastrectomy was more commonly performed than proximal gastrectomy (55.1% [109/198] vs. 47.0% [186/396], 1.5% [3/198] vs. 8.3% [33/396], χ2=11.644, P=0.003). Family history of gastric cancer, TNM stage, tumor size, lymph node dissection, nerve invasion, nodes harboring metastases, range of lymph node dissection, digestive tract reconstruction procedure, implementation of laparoscopic surgery, combined resection, and preoperative treatment did not differ significantly between the two groups (all P>0.05). Molecular diagnosis showed there was a smaller percentage of mismatch repair deficiency in the early-onset gastric cancer than in the control group (1.0% [2/198] vs. 10.1% [40/396], χ2=16.301, P<0.001), and a higher rate of positivity for Claudin 18.2 (77.8% [154/198] vs. 53.0% [210/396], χ2=5.442,P<0.001). HER-2 and Epstein-Barr virus positivity rates did not differ significantly between the two groups. Conclusion: Early-onset gastric cancer is a distinct type of gastric cancer with a high degree of malignancy, and treatment targeting Claudin 18.2 may be effective.
目的： 探讨早发型胃癌的临床病理特点，尤其是分子诊断特征，并分析其治疗策略。 方法： 采用回顾性病例对照研究方法。基于复旦大学附属中山医院胃癌专病数据库，收集2020年7月至2021年10月期间，于复旦大学附属中山医院普通外科行胃切除术的共2 506例胃癌患者的临床资料。其中，年龄≤45岁者198例，定义为早发型胃癌（早发型胃癌组）；另从2 308例非早发型胃癌患者按1∶2比例，采用简单随机抽样方法、选择396例患者作为对照（年龄>45岁，非早发型胃癌组）。对两组临床病理特征、分子诊断特征以及治疗策略进行比较。 结果： 早发型胃癌组中位年龄39岁，非早发型胃癌组则为66岁。相较非早发型胃癌组，早发型胃癌组以女性为主［59.1%（117/198）比27.8%（110/396），χ2=54.816，P<0.001］，合并症较少［32.3%（64/198）比57.1%（226/396），χ2=32.355，P<0.001］，低分化或未分化比例更高［93.9%（186/198）比74.5%（295/396），χ2=30.777，P<0.001］，Lauren分型弥漫型比例高［40.4%（80/198）比15.9%（63/396），χ2=69.639，P<0.001］，远处转移比例更高［7.1%（14/198）比2.8%（11/396），χ2=6.034，P=0.014］；在治疗上，远端胃切除比例高、近端胃切除比例低［分别为55.1%（109/198）比47.0%（186/396），1.5%（3/198）比8.3%（33/396），χ2=11.644，P=0.003］。两组在胃癌家族史、TNM分期、肿瘤大小、淋巴结清扫数、神经侵犯、癌结节以及淋巴结清扫范围、消化道重建方式、是否腹腔镜手术、是否行合并切除和术前治疗等方面比较，差异无统计学意义（均P>0.05）。分子诊断情况的比较，相比非早发型胃癌组，早发型胃癌错配修复基因缺陷比例更低［1.0%（2/198）比10.1%（40/396），χ2=16.301，P<0.001］，Claudin18.2阳性率较高［77.8%（154/198）比53.0%（210/396），χ2=5.442，P<0.001］。两组HER-2阳性比例和EBV+阳性比例差异无统计学意义（均P>0.05）。 结论： 早发型胃癌是一种恶性程度较高的特殊类型胃癌，Claudin18.2可能是其有效治疗靶点。.