The Impact of KPNA2 on Prognosis of Colorectal Cancer Patients: A Meta-Analysis

Background and purpose: Colorectal cancer (CRC) is one of the most common malignant tumors with the highest mortality globally. At present, there is no exact biomarker to predict the prognosis and clinicopathological monitoring of CRC patients. Recent studies on the relationship of Karyopherin α 2 (KPNA2) expression and the prognosis of CRC has gradually become a hot spot while the results are still controversial. The aim of this study was to analyze and assess the prognostic role of KPNA2 in CRC patients. Methods: PubMed, Web of Science, Medline, EMBASE, CNKI, Wanfang, VIP, and Chinese Medical Database were systematically searched. The cohort study of high-level expression of KNPA2 and low-level expression of KPNA2 in CRC patients was included, the relevant data were extracted and the literature quality was evaluated. At the same time, the relationship between KPNA2 expression level and the overall survival (OS), the clinicopathological stage of CRC patients was studied. Meta-analysis was carried out by Stata MP 17.0 (Stata Corporation, College Station, TX, USA) software. Results: A total of 7 cohort studies involving 1166 patients were included. The analysis results showed that higher KPNA2 expression was significantly associated with higher tumor stage (OR=1.90, 95% CI 1.42–2.54), higher degree of tumor invasion (OR=2.14，95% CI 1.55-2.94), more lymph node metastasis (OR=2.20, 95% CI 1.68-2.88) and more distant metastasis (OR=3.66，95% CI 1.81-7.40). Moreover, higher KPNA2 expression was significantly associated with the shorter OS (HR=2.31, 95%CI 1.46-3.68).Conclusion: KPNA2 overexpression is an unfavorable prognostic factor for CRC patients. It could serve as a prognostic biomarker and as a potential therapeutic target for CRC.

Correlation Between Cyclin D1 Expression With Different Pathological Changes in Colorectum Patients

Background: Cyclin D1 plays a vital role in cancer cell cycle progression and is overexpressed in many human cancers, including colorectal cancer. Objectives:This study was aimed to detect cyclin D1 in colorectal cancer patients and to correlate cyclin D1 expression with different pathological changes in colorectum.Methods: Tissues microarray paraffin block with 48 colorectal cancer samples were retrieved from the archives of Elrahma Medical Center. The cyclin D1 was analyzed.Results:Cyclin D1 did not correlate with pathological alterations and with tumor grade.Conclusion:Results indicated that; cyclin D1 not correlates with pathological alteration of colorectal cancer.

The Combination of Inflammation and Nutrition Factors Reinforces the Prognostic Prediction for Stage III Colorectal Cancer Patients After Curative Resection

Purpose Inflammation and nutritional status are known to be associated with the prognosis of several malignancies. Herein, we attempted to develop inflammation–nutrition scores and predict the prognosis of stage III colorectal cancer (CRC). Methods This retrospective study included 262 patients with stage III CRC who underwent curative surgery and were divided into two groups: a training set (TS) of 162 patients and a validation set (VS) of 100 patients. In the TS, clinicopathological factors were tested using a Cox regression model, and the Kansai prognostic score (KPS) was assessed by 1 point each for <3.5 g/dL albumin level, >450 monocyte counts, and <1.65 × 105 platelet counts, which were associated with disease-free survival (DFS). Using KPS, DFS and overall survival (OS) were validated in VS. Results The C-indices of KPS to predict DFS and OS in TS were 0.707 and 0.772. It was validated in VS that the C-indices of KPS to predict DFS and OS were 0.618 and 0.708, respectively. A high KPS was a significant predictor of DFS and OS. Conclusion KPS serves as a new model for the prognosis of patients with stage III CRC.

Epidermal Growth Factor Receptor as Target for Perioperative Elimination of Circulating Colorectal Cancer Cells

Surgical resection of the tumor is the primary treatment of colorectal cancer patients. However, we previously demonstrated that abdominal surgery promotes the adherence of circulating tumor cells (CTC) in the liver and subsequent liver metastasis development. Importantly, preoperative treatment with specific tumor-targeting monoclonal antibodies (mAb) prevented surgery-induced liver metastasis development in rats. This study investigated whether the epidermal growth factor receptor (EGFR) represents a suitable target for preoperative antibody treatment of colorectal cancer patients undergoing surgery. The majority of patients with resectable colorectal liver metastases were shown to have EGFR + CTCs. Three different anti-EGFR mAbs (cetuximab, zalutumumab, and panitumumab) were equally efficient in the opsonization of tumor cell lines. Additionally, all three mAbs induced antibody-dependent cellular phagocytosis (ADCP) of tumor cells by macrophages at low antibody concentrations in vitro, independent of mutations in EGFR signaling pathways. The plasma of cetuximab-treated patients efficiently opsonized tumor cells ex vivo and induced phagocytosis. Furthermore, neither proliferation nor migration of epithelial cells was affected in vitro, supporting that wound healing will not be hampered by treatment with low anti-EGFR mAb concentrations. These data support the use of a low dose of anti-EGFR mAbs prior to resection of the tumor to eliminate CTCs without interfering with the healing of the anastomosis. Ultimately, this may reduce the risk of metastasis development, consequently improving long-term patient outcome significantly.

Gastrointestinal Adenocarcinoma Incidence and Survival Trends in South Australia, 1990–2017

Background & Aims: Globally, there has been a concerning rise in the incidence of young-onset cancers. The aim of this study was to provide trends in the incidence and survival of gastrointestinal adenocarcinomas (oesophagus, stomach, pancreas, and colorectal) in South Australia over a 27-year period. Methods: This is a cross-sectional analysis of a prospective longitudinal database including all cases of gastrointestinal adenocarcinomas prospectively reported to the South Australian (State) Cancer Registry from 1990 to 2017. Results: A total of 28,566 patients diagnosed with oesophageal, stomach, pancreatic, or colorectal adenocarcinoma between 1990 and 2017 were included in the study. While the overall incidence for gastrointestinal adenocarcinomas in individuals >50 years has decreased since 2000 (IRR of 0.97 (95% CI 0.94–1.00; p = 0.06)) compared to 1990–1999, the rate amongst individuals aged 18–50 has significantly increased (IRR 1.41 (95% CI 1.27–1.57; p <0.001)) during the same reference time period. Although noted in both sexes, the rate of increase in incidence was significantly greater in males (11.5 to 19.7/100,000; p <0.001). The overall survival from adenocarcinomas across all subsites improved in the >50-year cohort in the last decade (HR 0.89 (95% CI 0.86–0.93; p <0.001)) compared to 1990–1999. In individuals aged 18–50 years, there has only been a significant improvement in survival for colorectal cancer (HR 0.82 (95% CI 0.68–0.99; p <0.04)), but not the other subsites. A lower overall survival was noted for males in both age cohorts (18–50 years—HR 1.24 (95% CI 1.09–1.13; p <0.01) and >50 years—HR 1.13 (95% CI 1.10–1.16; p <0.001), respectively) compared to females. Conclusions: This study from South Australia demonstrates a significant increase in young-onset gastrointestinal adenocarcinomas over the last 28 years, with a greater increase in the male sex. The only significant improvement in survival in this cohort has been noted in colorectal cancer patients.

68Ga-FAPI-04 PET Distinguishes Malignancy from Inflammatory Lesions

Background The 68Ga-labelled FAPI provides new oncology imaging option other than 18F-FDG-PET. However, it's unclear about whether the FAPI-PET distinguishes malignancy from benign lesions. Methods We established an AOM/DSS-induced rat colorectal tumor model. A double PET/CT tracer of 68Ga-FAPI-04 and 18F-FDG was used in the rat colorectal tumor model. Histological examination, immunohistochemistry staining, and radioautography were performed in this study. Results 68Ga-FAPI PET imaging distinguishes neoplasia from inflammatory lesions in an AOM/DSS-induced rat colorectal tumor model, and FAPI accumulation gradually increases along with tumor progression. An inflammatory lesion did not interfere with 68Ga-FAPI PET imaging. Conclusion The 68Ga-FAPI-04 PET distinguishes malignant tumors from inflammatory lesions by detecting FAP in a rat colorectal tumor model, suggesting that 68Ga-FAPI-04 PET is a better diagnostic tool than 18F-FDG PET, at least to colorectal cancer patients.