Characterization of CD 26+CD110+ (liver) and CD26+CDCP1+ (lung) cancer stem cell populations, determination of their mutational heterogeneity and the differences of the liver vs. lung niche

结直肠癌是男性和女性中第二常见的癌症。 在诊断时，25%的患者确实患有转移性疾病，50%的患者将在其疾病过程中发生转移。这种高转移率导致大多数患者最初不是根治性切除的候选者（1）。此外，器官特异性转移直接影响这些患者的总生存率。肝转移是最重要的预后因素之一。切除可以显著提高其生存率。除此之外，最近的数据显示，在存在不可切除的肺转移瘤的情况下切除所有肝转移瘤的患者的生存获益（2）。然而，与单纯结直肠肺转移患者相比，结直肠肝转移患者的预后确实要差得多（3）。因此，这表明结直肠肝转移和肺转移的肿瘤生物学存在差异。结肠直肠癌中的重要细胞亚群是癌症干细胞（CSC）转移，其赋予结肠直肠癌的生物学行为和侵袭性。癌症干细胞可以通过其表位检测，因此在转移的情况下也可以被识别。今天，没有进一步分析癌症干细胞的器官特异性转移已经进行，因此，结肠直肠肝和肺转移的侵袭性差异的原因仍然不清楚。该项目的目的是表征CD 26+ CD 110+（肝）和CD 26 + CDCP 1+（肺）癌症干细胞群体，确定其突变异质性以及肝与肺生态位的差异。

Colorectal cancer is the second most frequent cancer in men and women. At time of diagnosis 25% of patients do have metastatic disease and 50% of patients will develop metastases during the course of their disease. This high metastatic rate leads to the majority of patients initially not being candidates for curative resection (1). Further, organspecific metastases do directly impact on overall survival in these patients. Liver metastasis is one of the most important prognosticators. Their resection can significantly improve their survival. Adding to this, recent data has shown a survival benefit for patients in whom all liver metastases are resected in the presence of unresectable lung metastases (2). However, patients with colorectal liver metastases do have a considerably worse prognosis compared to patients with colorectal lung metastases alone (3). Therefore, this suggests that there are differences in tumor biology of colorectal liver and lung metastases. An important subpopulation of cells in colorectal cancer are cancer stem cells (CSC) metastasis that confer the biological behavior and aggressiveness of the colorectal cancer. Cancer stem cells can be detected by their epitopes and thus also be identified in case of metastasis. Today, no further analysis of cancer stem cells concerning organspecific metastasis has been performed and consequently the reason for the differences in aggressiveness of colorectal liver and lung metastases remains unclear. The aim of this project is the characterization of CD 26+CD110+ (liver) and CD26+CDCP1+ (lung) cancer stem cell populations, determination of their mutational heterogeneity and the differences of the liver vs. lung niche.