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Mol Cancer. 2016 Aug 24;15(1):55. doi: 10.1186/s12943-016-0539-x.

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.

Li Y1,2, Liang L1,2, Dai W1,2, Cai G1,2, Xu Y1,2, Li X1,2, Li Q3,4, Cai S5,6.

Author information

1
Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 20032, China.
2
Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 20032, China.
3
Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 20032, China. oncosurgeonli@sohu.com.
4
Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 20032, China. oncosurgeonli@sohu.com.
5
Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 20032, China. caisanjun_sh@163.com.
6
Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 20032, China. caisanjun_sh@163.com.

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.

KEYWORDS:

Colorectal cancer; PD-1; PD-L1; Prognosis; The cancer genome atlas; Tumor infiltrating lymphocytes

PMID:
27552968
PMCID:
PMC4995750
DOI:
10.1186/s12943-016-0539-x
[Indexed for MEDLINE]
Free PMC Article

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