Autophagy (A) related proteins evaluation represents an independent survival factor of colorectal cancer (CRC) patients (pts)
Authors: M. Karamouzis, A. Saetta, E. Koustas, I. Chatziandreou, I. Giannopoulou, M. Michelli, C. Giaginis, A. Papavassiliou, S. Theoharis
Journal: Annals of Oncology (2018)

Introduction: A holds a bimodal role during carcinogenesis. Before tumorigenesis, A promotes normal cells survival and suppress carcinogenesis, while after cancer development A induces cancer cells survival. The aim of this study is to assess the impact of A related proteins in the survival of CRC pts. Methods: The data of 68 CRC pts treated at our Department from January 1st to December 31st, 2016 were studied. KRAS, NRAS and BRAF status was evaluated with polymerase chain reaction, while MSI, p62 and LC3B with immunohistochemistry (IHC). IHC scoring of A related proteins was based on both the percentage of positive tumor cells and staining intensity. Statistical analysis was done using SPSS for Windows Software. Results: Patients' characteristics are shown in Table 1. Sixty-eight pts aged 34-81 years (median 66.4 years) were included. All pts were treated with chemotherapy (adjuvant or metastatic setting). By the time of the data evaluation (December 2017) 8 pts (11.8%) had died due to their disease. In cross-tabulation, p62 expression did not shown any significant association with clinicopathological parameters. Moreover, higher LC3B expression was more frequently observed in KRAS-positive CRC pts compared to KRAS-negative (p = 0.0550), whereas no correlation between LC3B expression and clinicopathological parameters was recorded. In univariate analysis, CRC pts having high p62 expression showed significantly better overall survival (OS) compared to those with low expression (24.8 vs 15.9 months; p = 0.008). In addition, CRC pts having high LC3B expression showed significantly better OS compared to those with low expression (24.9 vs 16.1 months; p = 0.007). In multivariate analysis, both p62 and LC3B expression were identified as independent prognostic factors of OS (p = 0.012 and p = 0.019, respectively), independently of tumor grade, disease stage and mutational status. CRC pts with high p62 expression also showed mildly better recurrence-free survival (RFS) compared to those with low expression (43.1 vs 34.8 months; p = 0.115), whereas high LC3B expression was not associated with better RFS (39.7 vs 38.4 months; p = 0.714).Table 1P-208 Patients' characteristics (n = 68)Gender Male 45 Female 23 Histology grade Grade I 4 Grade II 48 Grade III 16 Tumor size pT2 8 pT3 43 pT4 17 Lymph nodes pN0 26 pN1 27 pN2 15 Distant metastases M0 40 M1 28 K-RAS Negative 36 Positive 32 N-RAS Negative 64 Positive 4 B-RAF Negative 64 Positive 4 MSI Negative 64 Positive 4 Open table in a new tab Conclusion: Overall, these results indicate that the evaluation of A related proteins expression in paraffin specimens might represent an independent survival factor of CRC pts. The biological rationale could be the blockade of autophagy by chemotherapy resulting in high expression and accumulation of p62 and LC3B proteins. Further testing of other A related proteins (Beclin-1 and RAB7) is ongoing and will be presented.