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.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 20032, China.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 20032, China.
authors.forename: Yaqi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 20032, China.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 20032, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 20032, China.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 20032, China.
authors.forename: Weixing
authors.initials: W
authors.lastname: Dai
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 20032, China.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 20032, China.
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Cai
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 20032, China.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 20032, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 20032, China.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 20032, China.
authors.forename: Xinxiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 20032, China. oncosurgeonli@sohu.com.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 20032, China. oncosurgeonli@sohu.com.
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 20032, China. caisanjun_sh@163.com.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 20032, China. caisanjun_sh@163.com.
authors.forename: Sanjun
authors.initials: S
authors.lastname: Cai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000276:immunology; D030541:Databases, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Colorectal cancer; PD-1; PD-L1; Prognosis; The cancer genome atlas; Tumor infiltrating lymphocytes