Moffitt癌症中心的研究人员发现的基因突变，增殖之间的链接，在肺癌免疫监视

坦帕，佛罗里达州–学习如果肺癌患者的基因突变可以帮助医生确定治疗的最佳方法。有四个基因突变（KRAS基因基因基因基因，TP53，STK11，and 表皮生长因子受体) that most commonly occur in lung cancer; however，there are limited effective therapies to target these突变。 With this in mind，Moffitt Cancer Center performed an extensive genetic analysis of lung cancer specimens to unravel how mutations in the two of those genes (TP53和STK11) contribute to the biology of lung cancer和patient outcomes.

Patients with lung cancer have a 5-year survival rate of only 16 percent. “Given the low survival rates among lung cancer patients，there remains an urgent need to identify new genetic-based targets for precision-based medicine strategies，such as immune therapy.” explained Matthew B. Schabath，Ph.D.，assistant member of the Cancer Epidemiology Program at Moffitt

The researchers analyzed gene expression patterns in 442 lung adenocarcinomas和screened the tumors for gene mutations known to contribute to lung cancer development. They used this data to assess associations between genetic alterations，gene expression patterns和clinical outcomes. This is one of the largest studies of its kind和all data from the study was publically released to provide a new和valuable resource for cancer researchers worldwide. 

他们发现百分之34.8的肺肿瘤有KRAS基因基因基因基因 mutations，10.6 percent had mutations in 表皮生长因子受体，15.3 percent in STK11，and 25.1 percent in TP53。有肺腺癌患者KRAS基因基因基因基因突变比无患者生存期短KRAS基因基因基因基因突变。和肺癌患者有表皮生长因子受体突变有一个更好的总生存期比没有患者表皮生长因子受体突变。

Importantly，the researchers discovered that tumors with either TP53或STK11突变基因表达模式不同。肺肿瘤TP53 mutations had higher levels of genes that are associated with proliferation和growth，while lung tumors with STK11突变的基因水平较低，与免疫监视有关。 他们证实了这些结果显示，肿瘤STK11 mutations had reduced levels of immune cells或T cells.

“These findings could impact therapeutic treatments. Tumors can develop mechanisms to avoid immune detection，thereby allowing continued tumor growth,” said Schabath. Several agents currently in clinical development function by restimulating the immune system to target the tumor.  The data from the Moffitt researchers suggests that lung tumors with STK11突变可能对这些药物反应不太敏感。

“These studies reveal a novel link between common gene mutations和tumor immune surveillance. Therefore，gene mutations may also impact the response to immunotherapeutic agents，and targeting pathways controlled by these mutations could provide new opportunities for enhancing the immunotherapy response in patients,” said Amer A. Beg，Ph.D.，senior member of the Immunology Program at Moffitt.

The study was published online in the Oct. 19 issue of Oncogene，and was supported by a National Institutes of Health (NIH) SPORE Grant (P50 CA119997)和by a NIH Cancer Center Support Grant (CCSG Grant P30-CA76292) for Moffitt.

（注：转载时请注明复诊网）