Identification of Nectin Family Interactive Gene Panel and Stratification of Clinical Outcomes in Patients with Pancreatic Cancer.

BACKGROUND: Although patient-risk stratification is important for selecting individualized treatment for pancreatic ductal adenocarcinoma (PDAC), predicting the oncologic outcomes after surgery remains a challenge. In this study, we identified a nectin family gene panel (NFGP) that can accurately stratify oncologic outcomes in patients with PDAC. STUDY DESIGN: Comprehensive analysis of the expression of 9 nectin family genes identified the NFGP, which was assessed for predictive performance in 2 independent public cohorts (The Cancer Genome Atlas [TCGA] n = 176; International Cancer Genome Consortium [ICGC] n = 89). It was subsequently trained and validated for the in-house training cohort without neo-adjuvant therapy (NAT, n = 213) and the validation cohort with NAT (n = 307). RESULTS: Using the Cox regression model, NFGP derived from 9 nectin family genes accurately stratified overall survival (OS) in TCGA (p = 0.038) and ICGC (p = 0.005). We subsequently optimized NFGP, which robustly discriminated postoperative prognosis, OS (p = 0.014) and relapse-free survival ([RFS] p = 0.006) in the training cohort. The NFGP was successfully validated in an independent validation cohort (OS: p < 0.001; RFS: p = 0.004). Multivariate analysis demonstrated the NFGP was an independent prognostic factor for OS and RFS in the training (p = 0.028 and 0.008, respectively) and validation (p < 0.001 and 0.013, respectively) cohorts. The subcohort analyses showed that the predictive performance of NFGP is applicable to the patients' subcohort according to resectability or adjuvant therapy status. Additionally, a combination model of NFGP score and CA19-9 level emerged with improved accuracy for predicting prognosis. CONCLUSIONS: This study established the predictive significance of NFGP for oncologic outcomes after surgery in PDAC. Our data demonstrate its clinical impact as a potent biomarker for optimal patient selection for individualized treatment strategies.

Distinct role of tumor-infiltrating lymphocytes between synchronous and metachronous colorectal cancer.

PURPOSE: Tumor-infiltrating lymphocytes (TILs) may influence the prognosis of colorectal liver metastasis (CRLM). We assessed the prognostic value of evaluating TILs in the primary and metastatic sites of synchronous CRLM as well as metachronous CRLM. METHODS: We examined 90 patients who underwent curative primary and liver metastasis resection for colorectal cancer. CD8+ TILs (cytotoxic T cells) or CD45RO+ TILs (memory T cells) in both primary and metastatic sites were simultaneously evaluated by immunohistochemistry. RESULTS: Fifty-one patients had synchronous CRLM, and 39 patients had metachronous CRLM. In synchronous cases, the overall survival (OS) was significantly worse in patients with low CD8+ or CD45RO+ TILs in a metastatic site than in those with high CD8+ or CD45RO+ TILs (P = 0.017 and P = 0.005, respectively). Multivariate analysis showed that age ≥ 65 years (P = 0.043), maximum tumor size ≥ 30 mm (P = 0.003), primary N2-3 (P = 0.019), and low CD8+ TILs in metastatic site (P = 0.046) were independent poor prognostic factors. In contrast, in metachronous cases, OS was significantly worse in patients with low CD45RO+ TILs in a primary site than in those with high CD45RO+ TILs (P = 0.021). CD45RO+ TILs in a primary site (P = 0.044) were determined to be independent prognostic factor on multivariate analysis. CONCLUSIONS: The immune microenvironment between synchronous and metachronous CRLM might be different, and these differences may affect its prognosis.