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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.
- Source :
-
Molecular cancer [Mol Cancer] 2016 Aug 24; Vol. 15 (1), pp. 55. Date of Electronic Publication: 2016 Aug 24. - Publication Year :
- 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.<br />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.<br />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).<br />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.
- Subjects :
- Adult
Aged
Aged, 80 and over
B7-H1 Antigen metabolism
Colorectal Neoplasms immunology
Databases, Genetic
Female
Gene Expression Regulation, Neoplastic
Humans
Male
Middle Aged
Prognosis
Programmed Cell Death 1 Receptor metabolism
Survival Analysis
Tissue Array Analysis
B7-H1 Antigen genetics
Colorectal Neoplasms genetics
Lymphocytes, Tumor-Infiltrating metabolism
Programmed Cell Death 1 Receptor genetics
Up-Regulation
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4598
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular cancer
- Publication Type :
- Academic Journal
- Accession number :
- 27552968
- Full Text :
- https://doi.org/10.1186/s12943-016-0539-x