Tumor Inflammation, Obesity, and Proliferative Status as Biomarkers in Gastroesophageal Adenocarcinoma.
Tumor Inflammation, Obesity, and Proliferative Status as Biomarkers in Gastroesophageal Adenocarcinoma.
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DOI：
10.3390/jpm11121324
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发表时间：
2021-12-07
影响因子：
--
通讯作者：
Pabla S
中科院分区：
文献类型：
--
作者：
Mukherjee S;Seager RJ;Lee YH;Conroy JM;Kalinski P;Pabla S
最近的流行病学研究表明，肥胖，通常通过增加体重指数（BMI）来衡量，与胃食管腺癌（GEAC）的风险增加有关，但其分子和免疫机制仍不清楚。由于已知肥胖会促进慢性炎症，因此我们假设肥胖会导致炎症相关的免疫功能障碍，这可以通过免疫调节治疗逆转。为了验证我们的假设，我们检查了晚期GEAC患者的临床和分子数据。为此，对46例GEAC肿瘤进行了代表肿瘤炎症、细胞增殖和PD-L1表达的生物标志物评价。具有潜在协变量的CoxPH回归模型，随后进行成对事后分析，显示GEAC肿瘤微环境中的炎症与改善的总生存期相关，无论BMI如何。我们还观察到接受免疫调节治疗的超重个体的细胞增殖和无进展生存期之间存在显著相关性。总之，我们的数据证实了免疫系统在GEAC自然病程中的作用及其对免疫疗法的反应，但不支持BMI作为该组患者中独立的临床相关生物标志物的作用。
Recent epidemiological studies have shown that obesity, typically measured by increased body mass index (BMI), is associated with an increased risk of gastroesophageal adenocarcinoma (GEAC), but the contributing molecular and immune mechanisms remain unknown. Since obesity is known to promote chronic inflammation, we hypothesized that obesity leads to inflammation-related immune dysfunction, which can be reversed by immune-modulating therapy. To test our hypothesis, we examined the clinical and molecular data from advanced GEAC patients. To this end, 46 GEAC tumors were evaluated for biomarkers representing tumor inflammation, cell proliferation, and PD-L1 expression. A CoxPH regression model with potential co-variates, followed by pairwise post hoc analysis, revealed that inflammation in the GEAC tumor microenvironment is associated with improved overall survival, regardless of BMI. We also observed a significant association between cell proliferation and progression-free survival in overweight individuals who received immune-modulating therapy. In conclusion, our data confirm the role of the immune system in the natural course of GEAC and its responses to immunotherapies, but do not support the role of BMI as an independent clinically relevant biomarker in this group of patients.
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影响因子：
11.1
作者：
Pabla S;Seager RJ;Van Roey E;Gao S;Hoefer C;Nesline MK;DePietro P;Burgher B;Andreas J;Giamo V;Wang Y;Lenzo FL;Schoenborn M;Zhang S;Klein R;Glenn ST;Conroy JM
通讯作者：
Conroy JM
影响因子：
7
作者：
Aguilar EG;Murphy WJ
通讯作者：
Murphy WJ
影响因子：
254.7
作者：
Torre, Lindsey A.;Bray, Freddie;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
7.2
作者：
Zhang, Tian;Pabla, Sarabjot;Morrison, Carl
通讯作者：
Morrison, Carl
影响因子：
82.9
作者：
Wang, Ziming;Aguilar, Ethan G.;Monjazeb, Arta M.
通讯作者：
Monjazeb, Arta M.