Circulating tumor DNA (ctDNA) has emerged as a candidate biomarker for cancer screening. However, studies on the usefulness of ctDNA for postoperative recurrence monitoring are limited. The present study monitored ctDNA in postoperative blood by employing cancer-specific rearrangements. Personalized cancer-specific rearrangements in 25 gastric cancers were analyzed by whole-genome sequencing (WGS) and were employed for ctDNA monitoring with blood up to 12 months after surgery. Personalized cancer-specific rearrangements were identified in 19 samples. The median lead time, which is the median duration between a positive ctDNA detection and recurrence, was 4.05 months. The presence of postoperative ctDNA prior to clinical recurrence was significantly correlated with cancer recurrence within 12 months of surgery (P = 0.029); in contrast, no correlation was found between cancer recurrence and the presence of preoperative ctDNA, suggesting the clinical usefulness of postoperative ctDNA monitoring for cancer recurrence in gastric cancer patients. However, the clinical application of ctDNA can be limited by the presence of ctDNA non-shedders (42.1%, 8/19) and by inconsistent postoperative ctDNA positivity.

Background: Expression of transglutaminase 2 (TGase 2) is related to invasion and resistance to chemotherapeutic agents in several cancer cells. However, there has been only limited clinical validation of TGase 2 as an independent prognostic marker in cancer. Methods: The significance of TGase 2 expression as an invasive/migratory factor was addressed by in vitro assays employing down-regulation of TGase 2. TGase 2 expression as a prognostic indicator was assessed in 429 Korean patients with early-stage non-small cell lung cancer (NSCLC) by immunohistochemical staining. Results: TGase 2 expression increased the invasive and migratory properties of NSCLC cells in vitro, which might be related to the induction of MMP-9. In the analysis of the immunohistochemical staining, TGase 2 expression in tumors was significantly correlated with recurrence in NSCLC (p = 0.005) or in the non-adenocarcinoma subtype (p = 0.031). Additionally, a multivariate analysis also showed a significant correlation between strong TGase 2 expression and shorter disease-free survival (DFS) in NSCLC (p = 0.029 and HR = 1.554) and in the non-adenocarcinoma subtype (p = 0.030 and HR = 2.184). However, the correlation in the adenocarcinoma subtype was not significant. Conclusions: TGase 2 expression was significantly correlated with recurrence and shorter DFS in NSCLC, especially in the non-adenocarcinoma subtype including squamous cell carcinoma.

The level of proliferation activity is a strong prognostic or predictive indicator in breast cancer, but its optimal measurement is still in debate, necessitating new proliferation markers. In the present study, the prognostic significance of the CKAP2-positive cell count (CPCC), a new proliferation marker, was evaluated, and the results were compared with those for the mitotic activity index (MAI). This study included 375 early-stage breast cancer samples collected from two institutions between 2000 and 2006. Immunohistochemical staining was performed using a CKAP2 monoclonal antibody. Cox proportional hazard regression models were fitted to determine the association between the CPCC and relapse-free survival (RFS) amongst three groups formed on the basis of the CPCC or MAI value: groups 2 and 3 showing the middle and highest values, respectively, and group 1 the lowest. After adjustment for age, T stage, N stage, HER2 status, estrogen receptor status, progesterone receptor status, institution, and year of surgical resection, the CPCC was associated with a significantly worse RFS {hazard ratio [HR] = 4.10 (95% CI: 1.64–10.29) for group 2; HR = 4.35 (95% CI: 2.04–10.35) for group 3}. Moreover, its prognostic significance was similar to or higher than that based on the MAI {HR = 2.05 (95% CI: 0.94–4.65) for group 2; HR = 2.35 (95% CI: 1.09–5.10) for group 3}. In subgroup analyses, the CPCC showed a prognostic significance in the luminal A and triple-negative subgroups, but not in the HER2-positive subgroup. Chromatin CKAP2 is an independent prognostic marker for RFS in early-stage breast cancer, and could potentially replace the MAI in clinical evaluation of proliferation activity. Additionally, our study results suggest that the prognostic significance of proliferation activity differs among the various subgroups of breast cancer.

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More than 11,000 laboratories and companies developed their own next-generation sequencing (NGS) for screening and diagnosis of various diseases including cancer. Although inconsistencies of mutation calls as high as 43% in databases such as GDSC (Genomics of Drug Sensitivity in Cancer) and CCLE (Cancer Cell Line Encyclopedia) have been reported, not many studies on the reasons for the inconsistencies have been published. Methods: Targeted-NGS analysis of 151 genes in 35 cell lines common to GDSC and CCLE was performed, and the results were compared with those from GDSC and CCLE wherein whole-exome- or highly-multiplex NGS were employed. In the comparison, GDSC and CCLE had a high rate (40–45%) of false-negative (FN) errors which would lead to high rate of inconsistent mutation calls, suggesting that highly-multiplex NGS may have high rate of FN errors. We also posited the possibility that targeted NGS, especially for the detection of low-level cancer cells in cancer tissues might suffer significant FN errors. FN errors may be the most important errors in NGS testing for cancer; their evaluation in laboratory-developed NGS tests is needed.