Nomogram constructed by immunological and inflammatory indicators for predicting prognosis of patients with esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy plus surgery.

Objectives: At present, esophageal squamous cell carcinoma (ESCC) patients accepting neoadjuvant chemoradiotherapy (nCRT) plus surgery lack corresponding prognostic indicators. This study aimed to construct a prognostic prediction model for ESCC patients undergoing nCRT and surgery based on immune and inflammation-related indicators. Methods: We retrospectively analyzed the levels of serum immune- and inflammation-related indicators of ESCC patients before receiving nCRT plus surgery in the training cohort (99 patients) and validation cohort (67 patients), which were collected from 2007 to 2020. Univariate and multivariate Cox survival analyses were conducted to evaluate the indicators to set up a nomogram associated with the patients' overall survival (OS). The prediction accuracy and discriminative ability of the nomogram were measured by the concordance index (C-index), decision curve, calibration curve, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). Results: Univariate and multivariate Cox analyses demonstrated that immune globin A (IgA) and C-reactive protein (CRP) were independent risk factors. A nomogram based on IgA, CRP, and cTNM stage was established for predicted OS in the training cohort and validated in the validation cohort. The C-index of the nomogram was 0.820 (95% CI: 0.705-0.934), which was higher than that of the cTNM stage (0.655 (95% CI: 0.546-0.764), p < 0.05) in the training cohort, and similar results were observed in the validation cohort (0.832 (95% CI: 0.760-0.903 vs 0.635 (95% CI: 0.509-0.757), p < 0.001). Furthermore, the prediction accuracy and net benefit of the nomogram verified by the calibration curve, decision curve, NRI, and IDI were satisfactory in the training and validation cohorts. Conclusion: The newly constructed nomogram concluding serum IgA, CRP, and cTNM stage might be helpful in the prognosis prediction for ESCC patients receiving nCRT plus surgery.

A Panel of Tumor-associated Autoantibodies for the Detection of Early-stage Breast Cancer.

We previously found a panel of autoantibodies against multiple tumor-associated antigens (BMI-1, HSP70, MMP-7, NY-ESO-1, p53 and PRDX6) that might facilitate early detection of esophagogastric junction adenocarcinoma and esophageal squamous cell carcinoma. Here we aimed at assessing the diagnostic performance of these autoantibodies in breast cancer patients. Enzyme-linked immunosorbent assay was applied to detect sera autoantibodies in 123 breast cancer patients and 123 age-matched normal controls. We adopted logistic regression analysis to identify optimized autoantibody biomarkers for diagnosis and receiver-operating characteristics to analyze diagnostic efficiency. Five of six autoantibodies, BMI-1, HSP70, NY-ESO-1, p53 and PRDX6 demonstrated significantly elevated serum levels in breast cancer compared to normal controls. An optimized panel composed of autoantibodies to BMI-1, HSP70, NY-ESO-1 and p53 showed an area under the curve (AUC) of 0.819 (95% CI 0.766-0.873), 63.4% sensitivity and 90.2% specificity for diagnosing breast cancer. Moreover, this autoantibody panel could differentiate patients with early stage breast cancer from normal controls, with AUC of 0.805 (95% CI 0.743-0.886), 59.6% sensitivity and 90.2% specificity. Our findings indicated that the panel of autoantibodies to BMI-1, HSP70, NY-ESO-1 and p53 as serum biomarkers have the potential to help detect early stage breast cancer.

IGFBP-1 in cancer: expression, molecular mechanisms, and potential clinical implications.

Insulin-like growth factor binding protein-1 (IGFBP-1) belongs to the insulin-like growth factor (IGF) system, which plays an indispensable role in normal growth and development, and in the pathophysiology of various tumors. IGFBP-1 has been shown to be associated with the risk of various tumors, and has a vital function in regulating tumor behaviors such as proliferation, migration, invasion and adhesion through different molecular mechanisms. The biological actions of IGFBP-1 in cancer are found to be related to its phosphorylation state, and the IGF-dependent and -independent mechanisms. In this review, we provided an overview of IGFBP-1 in normal physiology, and its aberrantly expression and the underlying molecular mechanisms in a range of common tumors, as well as discussed the potential clinical implications of IGFBP-1 as diagnostic or prognostic biomarkers in cancer.

IGFBP2 in cancer: Pathological role and clinical significance (Review).

The versatility of IGFBP2, as a secreted protein in cancer cells or a cytoplasmic signaling effector, has been extensively investigated in many malignant cancers. Over the last few decades, IGFBP2, a key member of the IGFBP family, has been identified as an important oncogene in multiple human cancers. In addition, a growing number of studies have shown that IGFBP2 is greatly elevated in serum or tissue in patients with malignant tumors and plays an essential role in several key oncogenic processes, such as tumor cellular proliferation, migration, invasion, angiogenesis, epithelial­to­mesenchymal transition, and immunoregulation, which are involved in a variety of signal pathways, usually via an IGF­independent means. Moreover, growing evidence indicates that aberrant overexpression of IGFBP2 may serve as a useful biomarker for the diagnosis and prognosis of patients, as well as act as a potential therapeutic target for the management of clinical treatment in patients with malignant disease. In the present review, we summarize the current points of view that IGFBP2 performs a role in the initiation and progression of various types of cancer by interacting with several key molecules involved in cancer signaling pathways. We also discuss its potential clinical application value as a diagnostic/prognostic biomarker for patients with malignant tumors.

Blood-based biomarkers for early detection of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor of the digestive system worldwide, especially in China. Due to the lack of effective early detection methods, ESCC patients often present at an advanced stage at the time of diagnosis, which seriously affects the prognosis of patients. At present, early detection of ESCC mainly depends on invasive and expensive endoscopy and histopathological biopsy. Therefore, there is an unmet need for a non-invasive method to detect ESCC in the early stages. With the emergence of a large class of non-invasive diagnostic tools, serum tumor markers have attracted much attention because of their potential for detection of early tumors. Therefore, the identification of serum tumor markers for early detection of ESCC is undoubtedly one of the most effective ways to achieve early diagnosis and treatment of ESCC. This article reviews the recent advances in the discovery of blood-based ESCC biomarkers, and discusses the origins, clinical applications, and technical challenges of clinical validation of various types of biomarkers.