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Molecular Cancer

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Open Access 01-12-2016 | Research

Prognostic impact of programed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor infiltrating lymphocytes in colorectal cancer

Authors: Yaqi Li, Lei Liang, Weixing Dai, Guoxiang Cai, Ye Xu, Xinxiang Li, Qingguo Li, Sanjun Cai

Published in: Molecular Cancer | Issue 1/2016

Abstract

Background

Colorectal cancer (CRC) is 3rd most commonly diagnosed cancer in males and the second in females. PD-1/PD-L1 axis, as an immune checkpoint, is up-regulated in many tumors and their microenvironment. However, the prognostic value of PD-1/PD-L1 in CRC remains unclear.

Methods

The Cancer Genome Atlas (TCGA) database (N = 356) and Fudan University Shanghai Cancer Center (FUSCC) cohort of patients (N = 276) were adopted to analyze the prognostic value of PD-L1 in colorectal tumor cells (TCs) and of PD-1 in tumor infiltrating cells (TILs) for CRC. Subgroup analyses were conducted in FUSCC cohort according to patients’ status of mismatch repair.

Results

In TCGA cohort, the cut-off values of PD-1 and PD-L1 expression were determined by X-tile program, which were 4.40 and 2.92, respectively. Kaplan-Meier analysis indicated that higher PD-1 and PD-L1 expressions correlated with better OS (P = 0.032 and P = 0.002, respectively). In FUSCC cohort, expressions of PD-1 on TILs and PD-L1 on TCs were analyzed separately by immunohistochemistry (IHC) staining based on a TMA sample (N = 276) and revealed that both TILs-PD-1 and TCs-PD-L1 were associated with OS (P = 0.006 and P = 0.002, respectively) and DFS (P = 0.025 and P = 0.004, respectively) of CRC patients. Multivariate Cox regression analysis indicated TILs-PD-1 was an independent prognostic factor both for OS and DFS of CRC patients (P < 0.05). Subgroup analyses showed that TILs-PD-1 was an independent prognostic factor for both OS and DFS in CRC patients in MSS-proficient subgroup (P < 0.05), while neither of them correlated with OS or DFS in MSS-deficient subgroup (P > 0.05).

Conclusions

Higher expressions of PD-1 and PD-L1 correlates with better prognosis of CRC patients. TILs-PD-1 is an independent prognostic factor for OS and DFS of CRC patients, especially for MMR-proficient subgroup.

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Title: Prognostic impact of programed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor infiltrating lymphocytes in colorectal cancer
Authors: Yaqi Li
Lei Liang
Weixing Dai
Guoxiang Cai
Ye Xu
Xinxiang Li
Qingguo Li
Sanjun Cai
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2016
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/s12943-016-0539-x

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