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Objective: PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) regulates components of the cell cycle, including cell growth, immune responses, DNA damage repair, apoptosis, and inflammation. PBK/TOPK may also accelerate tumorigenesis in colorectal cancer. Methods: We investigated the impact of PBK/TOPK on the clinical outcome of colorectal cancer patients to further identify its role in colorectal cancer. PBK/TOPK immunoreactivity was analyzed by immunohistochemistry in 162 cancer specimens from primary colorectal cancer patients. Results: The mean follow-up time after surgery was 5.4 years (medium: 3.9 years; range 0.01 to 13.1 years). The prognostic value of PBK/TOPK on overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models. PBK/TOPK was expressed in both the cytoplasm and nucleus. High PBK/TOPK expression in tumor cells was significantly associated with advanced T value. The 5-year survival rate was greater for patients with high total PBK/TOPK expression than with low PBK/TOPK expression (58.3% vs 34.4%, P = 0.005). Multivariate analyses showed that low-scoring cytoplasmic PBK/TOPK, negative nuclear PBK/TOPK, low total PBK/TOPK, and advanced tumor stage were correlated with poor overall patient survival. Conclusions: We suggest that PBK/TOPK expression, detected by IHC staining, could be used as an independent prognostic marker for colorectal cancer patients. [ABSTRACT FROM AUTHOR]

PD-L1 has been widely demonstrated to contribute to failed antitumor immunity. Blockade of PD-L1 with monoclonal antibody could modulate the tumor immune environment to augment immunotherapy. PD-L1 expression is also detected in several types of cancer and is associated with poor prognosis. However, the prognostic role of PD-L1 in oral squamous cell carcinoma (OSCC) is still controversial. Our aim was to determine the role of PD-L1 in the prognosis of OSCC patients to identify its potential therapeutic relevance. PD-L1 immunoreactivity was analyzed by immunohistochemistry in 305 cancer specimens from primary OSCC patients. The medium follow-up time after surgery was 3.8 years (range from 0.1 to 11.1 years). The prognostic value of PD-L1 on overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models. Higher PD-L1 expression is more likely in tumor tissues of female than male OSCC patients (P = 0.0062). Patients with distant metastasis also had high PD-L1 expression (P = 0.0103). Multivariate analysis identified high PD-L1 expression as an independent risk factor in males and smokers (males: hazard ratio = 1.556, P = 0.0077; smokers: hazard ratio = 2.058, P = 0.0004). We suggest that PD-L1 expression, determined by IHC staining, could be an independent prognostic marker for OSCC patients who are male or who have a smoking habit. [ABSTRACT FROM AUTHOR]

Synthetic lethality arises when a combination of mutations in two or more genes leads to cell death. However, the prognostic role of concordant overexpression of synthetic lethality genes in protein level rather than a combination of mutations is not clear. In this study, we explore the prognostic role of combined overexpression of paired genes in lung adenocarcinoma. We used immunohistochemical staining to investigate 24 paired genes in 93 lung adenocarcinoma patients and Kaplan-Meier analysis and Cox proportional hazards models to evaluate their prognostic roles. Among 24 paired genes, only FEN1 (Flap endonuclease 1) and RAD54B (RAD54 homolog B) were overexpressed in lung adenocarcinoma patients with poor prognosis. Patients with expression of both FEN1 and RAD54B were prone to have advanced nodal involvement and significantly poor prognosis (HR = 2.35, P = 0.0230). These results suggest that intensive follow up and targeted therapy might improve clinical outcome for patients who show expression of both FEN1 and RAD54B. [ABSTRACT FROM AUTHOR]

Abstract: Background: Interleukin 10 (IL10) plays an important role in immunosuppression and suppression of antitumor immunity. This study examined the IL10 expression of tumor cells and assessed its significance in patients with oral squamous cell carcinoma (OSCC). Methods: Tumor tissues and adjacent normal tissues were obtained from 325 patients with OSCC and were arranged in a tissue microarray. We examined 325 surgical specimens for associations between IL10 expression in tumor cells and clinical parameters of oral cancer. Results: High IL10 expression in OSCC patients was significantly associated with male gender (P<0.001), smoking (P=0.015), alcohol consumption (P=0.018), betel quid chewing (P=0.003), poor relapse free survival (P=0.012), and poor overall survival (P=0.001). Patients with high IL10 expression, and particularly early stage OSCC patients, had significantly worse overall survival as defined by the log-rank test (P=0.014 for all cases; P=0.004 for early stage patients). In early stage patients, high IL10 expression in tumor cells was associated with poor prognosis (P=0.018) and a 1.99-fold higher death risk, as determined by Cox regression. Conclusion: High IL10 expression is significantly associated with aggressive clinical manifestations and might be an independent survival predictor, particularly in early stage OSCC patients. [Copyright &y& Elsevier]

Aims: Epidermal growth factor receptor pathway substrate 8 (Eps8) is a signaling protein implicated in the development of many human cancers including oral squamous cell carcinoma (OSCC). This study examined the expression of Eps8 and assessed its significance in patients with OSCC. Methods: Immunohistochemical staining for Eps8 was conducted in 205 cases of OSCC collected over 7 years. The results were analyzed and correlated with patients' clinical outcomes. Results: We identified Eps8 expression in 186 of the 205 cases of OSCC (91%) and the aberrance occurred primarily in the cytoplasm of OSCC cells. Univariate analysis revealed that patients with Eps8 expression had significantly poorer 5-year overall survival (OS) than those without it (43% vs 74%, P = 0.014). Eps8 expression was also identified as an independent predictive factor for poorer OS by a multivariate analysis in regression modeling ( P = 0.021, HR = 2.7). A Kaplan-Meier analysis showed that patients with positive Eps8 expression had a significantly poorer OS than patients with negative/low Eps8 expression ( P = 0.038). The difference in disease-free survival between positive Eps8 expression and negative/low Eps8 expression nearly reached statistical significance ( P = 0.051). Conclusion: Eps8 is frequently expressed in OSCC. The aberrant expression of Eps8 closely correlated with poor survival in patients with OSCC. [ABSTRACT FROM AUTHOR]

Predictive metabolic biomarkers for the recurrent luminal breast cancer (BC) with hormone receptor (HR)-positive and human epidermal growth factor receptor type 2 (HER2)-negative are lacking. High levels of O-GlcNAcylation (O-GlcNAc) and pyruvate kinase isoenzyme M2 (PKM2) are associated with malignancy in BC; however, the association with the recurrence risk remains unclear. We first conduct survival analysis by using the METABRIC dataset to assess the correlation of PKM2 expression with BC clinical outcomes. Next, patients with HR+/HER2- luminal BC were recruited for PKM2/O-GlcNAc testing. Logistic regression and receiver operating characteristic curve analysis were performed to evaluate the 10-year DFS predicted outcome. Survival analysis of the METABRIC dataset revealed that high expression of PKM2 was significantly associated with worse overall survival in luminal BC. The high expression of O-GlcNAc or PKM2 was a significant independent marker for poor 10-year DFS using immunohistochemical analysis. The PKM2 or O-GlcNAc status was a significant predictor of DFS, with the combination of PKM2–O-GlcNAc status and T stage greatly enhancing the predictive outcome potential. In summary, O-GlcNAc, PKM2, and T stage serve as good prognostic discriminators in HR+/HER2− luminal BC. [ABSTRACT FROM AUTHOR]

Background: Current advancements in neoadjuvant therapy and total mesorectal excision have engendered increased local control. However, the survival benefit of preoperative radiotherapy (RT; 5 × 5 Gy) in rectal cancer patients remains inadequate, primarily because of systemic recurrence. In this retrospective single-center study, the effects of monthly tegafur-uracil maintenance (≥6 cycles) after 12 fluorouracil-based adjuvant chemotherapy cycles on 3-year relapse-free survival (RFS) was estimated in ypStage III rectal cancer patients.Methods: Of ypStage III rectal cancer patients who received preoperative RT (5 × 5 Gy) in January 2006-December 2015, those who had ypStage III cancer after preoperative radiation, radical resection, and postoperative chemotherapy were enrolled; excluded patients had ypStage I and II rectal cancer, had double cancer, had synchronous distant metastasis, had local excision, received preoperative chemoradiation, and were lost to follow-up within 1 year after cancer treatment. Included patients received either maintenance therapy or observation after postoperative chemotherapy. The primary endpoint was the effect of maintenance therapy on 3-year RFS. We set the median follow-up duration to be 69.7 (range, 15.4-148.3) months.Results: Of 259 ypStage III rectal cancer patients, 102 (59 men and 43 women) were enrolled based on the inclusion criteria. The maintenance and observation groups comprised 55 and 57 patients, respectively (mean age = 62.2 and 65.7 years, respectively; p = 0.185). The 3-year RFS observed in the maintenance group (85.1%) was longer than that observed in the observation group (67.5%; p = 0.039). Multivariate analysis proved the following to be independent prognostic factors for RFS: higher metastatic lymph node ratio (LNR ≥0.3), tegafur-uracil maintenance (≥6 cycles), and lower rectal cancer (< 6 cm from the anal verge). The higher the rectal cancer location (≥6 cm from the anal verge) was, the higher the tegafur-uracil maintenance survival benefit became (p = 0.041). Moreover, lower cancer location (< 6 cm from the anal verge) and LNR ≥0.3 were both associated with a trend of longer RFS after tegafur-uracil maintenance therapy (p = 0.164 and 0.113, respectively).Conclusions: After the execution of fluorouracil-based adjuvant chemotherapy, administering monthly tegafur-uracil (≥6 cycles) may improve the 3-year RFS of ypStage III rectal cancer patients. [ABSTRACT FROM AUTHOR]