Parida Sheetal, Siddharth Sumit, Sharma Dipali
Department of Oncology, Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA.
Cancers (Basel). 2021 Jan 13;13(2):275. doi: 10.3390/cancers13020275.
Lung cancer remains the second-most-common cancer worldwide and is associated with the highest number of cancer-related mortality. While tobacco smoking is the most important risk factor for lung cancer, many other lifestyles and occupational factors significantly contribute. Obesity is a growing global health concern and contributes to ~30% cancer-related mortality, but unlike other lifestyle diseases, lung cancer is negatively associated with obesity. We meta-analyzed multiple case-control studies confirming increased survival and better outcomes in overweight and obese lung cancer patients. Tumor heterogeneity analysis showed significant enrichment of adipocytes and preadipocytes in normal lungs compared to lung cancers. Interestingly, one of the understudied adipokine, omentin, was significantly and consistently lower in lung neoplasms compared to normal lungs. Omentin has been examined in relation to osteoarthritis, inflammatory bowel disease, cardiovascular diseases, diabetes, chronic liver disease, psoriasis and some other cancers. Aberrant expression of omentin has been reported in solid tumors; however, little is known about its role in lung cancer. We found omentin to be consistently downregulated in lung cancers, and it exhibited a negative correlation with important transcription factors FOXA1, EN1, FOXC1 and ELK4. We, therefore, suggest that omentin may serve as a prognostic factor in lung cancer and explain the "obesity paradox" in lung cancer.
肺癌仍然是全球第二大常见癌症，且与癌症相关死亡率最高相关。虽然吸烟是肺癌最重要的风险因素，但许多其他生活方式和职业因素也有显著影响。肥胖是一个日益引起全球关注的健康问题，导致约30%的癌症相关死亡，但与其他生活方式疾病不同，肺癌与肥胖呈负相关。我们对多项病例对照研究进行了荟萃分析，证实超重和肥胖的肺癌患者生存率提高且预后更好。肿瘤异质性分析显示，与肺癌相比，正常肺组织中脂肪细胞和前脂肪细胞显著富集。有趣的是，与正常肺组织相比，肺癌组织中一种研究较少的脂肪因子网膜素显著且持续降低。网膜素已在骨关节炎、炎症性肠病、心血管疾病、糖尿病、慢性肝病、银屑病和其他一些癌症中进行了研究。在实体瘤中已报道了网膜素的异常表达；然而，其在肺癌中的作用知之甚少。我们发现网膜素在肺癌中持续下调，并且它与重要转录因子FOXA1、EN1、FOXC1和ELK4呈负相关。因此，我们认为网膜素可能作为肺癌的一个预后因素，并解释肺癌中的“肥胖悖论”。
