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Laminin is an extracellular matrix molecule that is the major component of the basement membrane and plays a key role in regulating various processes. However, the association between the laminin gene family and the prognosis of pancreatic carcinoma has not been systematically investigated. The role of the laminin gene family in pancreatic cancer was evaluated using data from the TCGA database. The effects of different expressions of members of the laminin gene family on pancreatic cancer survival were compared, and their primary cellular roles were examined. The effects of different expressions of positive family genes on proliferation, metastasis, and invasion, as well as EMT and ferroptosis in pancreatic cancer, were also examined. Based on univariate and multifactorial analysis of pancreatic cancer patients, LAMA3 was identified as an independent prognostic factor for overall survival in pancreatic cancer. LAMA3 was found to be enriched in the actin cytoskeleton, P53 signaling pathway, adhesion molecule junctions, pentose phosphate pathway, and regulatory differences in the cell cycle and focal adhesion. Additionally, high expression of LAMA3 was found to promote cancer proliferation, invasion, and metastasis, facilitate the EMT process, and inhibit ferroptosis. Our results identified LAMA3 was associated with the prognosis of patients with pancreatic cancer and may serve as a prognostic biomarker for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Introduction: Factors associated with prognosis and molecular mechanisms leading to a malignant phenotype in head and neck squamous cell carcinoma (HNSCC) need to be identified. The focus was on the biological function and clinical impact of hepatitis B X‐interacting protein (HBXIP) in HNSCC. Methods: mRNA expression profiles of HBXIP were compared between tumor and normal tissues in head and neck cancer cases from an online database. The protein expressions of candidate genes were verified by immunohistochemistry (IHC) with tissue microarray blocks designed with 221 cases. Prognostic significance was analyzed using the Kaplan–Meier method and Cox regression analysis. The molecular function of malignant phenotypes was investigated by generating knockdown cell lines of HNSCC with RNA interference. Results: Analysis of the online database showed that the mRNA of HBXIP was significantly higher in the HNSCC group than in normal specimens. IHC analysis showed significant differences in the protein expression of HBXIP by clinical stage, T status, and recurrence. Multivariate analysis showed that, in HBXIP IHC‐positive patients, N status, T status, and neural invasion were significantly associated with overall survival. In addition, downregulation of the HBXIP gene in SAS, a tongue squamous cancer cell line, inhibited proliferation and the invasion phenotype. Conclusions: By increasing the malignant phenotypes of cell proliferation and invasion, upregulation of HBXIP was a prognostic factor in HNSCC. [ABSTRACT FROM AUTHOR]

• 177Lu-PSMA is a new option in PSMA-positive metastatic castration-resistant (mCRPC) patients. • A high proportion of patients do not respond 177Lu-PSMA. • Prognostic and predictive biomarkers for 177Lu-PSMA are under investigation. • The identification of biomarkers is essential for optimizing the use of 177Lu-PSMA in this setting. 177Lu-PSMA has been approved for the treatment of PSMA-positive metastatic castration-resistant (mCRPC) patients who progressed to androgen receptor pathway inhibitors (ARPIs) and taxane-based chemotherapy. However, a higher proportion of patients do not respond to this type of radioligand therapy (RLT). To date, there is a lack of validated prognostic and predictive biomarkers for 177Lu-PSMA therapy in prostate cancer. Several studies have investigated the prognostic and predictive role of clinical and molecular factors and also the metabolic features of PET imaging. In this review, we aim to take stock of the current scenario, focusing on new emerging data from retrospective/prospective series and clinical trials. Given the high costs and the possibility of primary resistance, it seems essential to identify clinical and molecular characteristics that could allow clinicians to choose the right patient to treat with 177Lu-PSMA. Biomarker-based clinical trials are urgently needed in this field. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text Objective: Our aim was to determine the prognostic significance of the systemic-immune-inflammation index (SIII) in patients with resectable pancreatic cancer, using cancer-specific survival as the primary outcome. Background: Pancreatic cancer is associated with a dysfunctional immune system and poor prognosis. We examined the prognostic significance of the SIII in patients with resectable pancreatic ductal adenocarcinoma (PDAC) and the effects of bilirubin on this index. Methods: We retrospectively assessed all pancreatic resections performed between 2004 and 2015 at 4 tertiary referral centers to identify pathologically confirmed PDAC patients. Baseline clinicopathologic characteristics, preoperative laboratory values such as absolute neutrophil, lymphocyte, and platelet counts, C-reactive protein, albumin, bilirubin, and CA19-9 levels, and also follow-up information, were collected. The associations of the calculated inflammatory indices with outcome were both internally and externally validated. Results: In all, 590 patients with resectable PDAC were included. The discovery and validation cohort included 170 and 420 patients, respectively. SIII >900 [hazard ratio (HR) 2.32, 95% confidence interval (CI) 1.55–3.48], lymph node ratio (HR 3.75, 95% CI 2.08–6.76), and CA19.9 >200 kU/L (HR 1.62, 95% CI 1.07–2.46) were identified as independent predictors of cancer-specific survival. Separate model analysis confirmed that preoperative SIII contributed significantly to prognostication. However, SIII appeared to lose its prognostic significance in patients with bilirubin levels above 200 μmol/L. Conclusions: SIII is an independent predictor of cancer-specific survival and recurrence in patients with resectable PDAC. SIII may lose its prognostic significance in patients with high bilirubin levels. Properly designed prospective studies are needed to further confirm this hypothesis. [ABSTRACT FROM AUTHOR]

Abstract: Metastasis is a major cause of cancer deaths. Seeking alternative prognostic biomarkers may enable oncologists to make accurate therapeutic decisions to benefit cancer patients. Cumulated evidence reveals that fibronectin (FN) is highly correlated with cancer metastasis but has not been deemed as a prognostic biomarker due to its broad tissue distribution patterns and complicated physiological and pathological functionalities that significantly interfere with the judgmental accuracy. Combining other FN-related factors may make FN possible as a useful prognostic biomarker. Clathrin, a highly protease-susceptible cytoplasmic molecule, is known to affect pericellular FN (periFN) assembly via regulating cell surface FN receptors or FN matrix turnover by coating the endocytic vesicles. Researching our previously published proteomics database of 660 differential secretome proteins expressed in human lung adenocarcinoma cell lines and performing double immunofluorescent staining for periFN and clathrin, we recognized an inverse relationship between them. However, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) data contradicted this relationship, which could be corrected by the addition of a mixture of protease inhibitors into nonmetastatic cancer cell lysates. These results suggested that nonmetastatic cells express either higher levels of cellular proteases or less amounts of protease inhibitors. By examining our proteomic database and reviewing the literature, we conclude that clathrin expression and assembly is inversely correlated with metastatic potential of FNhigh cancer cells mainly related to the expression of protease inhibitors, instead of proteases. It is worth investigating whether such an inverse relationship between FN/protease inhibitors and clathrin in human cancers could clinically be incorporated into the prognostic strategy for various cancer types. [Copyright &y& Elsevier]

The application of imaging biomarkers in oncology is still in its infancy, but with the expansion of radiomics and radiogenomics a revolution is expected in this field. This may be of special interest in head and neck cancer, since it can promote precision medicine and personalization of treatment by overcoming several intrinsic obstacles in this pathology. Our goal is to provide the medical oncologist with the basis to approach these disciplines and appreciate their main uses in clinical research and clinical practice in the medium term. Aligned with this objective we analyzed the most relevant studies in the field, also highlighting novel opportunities and current challenges. [ABSTRACT FROM AUTHOR]

Background : Methotrexate is the most common first-line chemotherapy for low-risk gestational trophoblastic neoplasia (GTN). Uterine artery pulsatility index (UAPI) is an ultrasound marker for tumor vascularity that has been associated with an increased risk of methotrexate resistance. The combination of circulating angiogenic factor levels with UAPI data may improve the capacity of this model to predict chemoresistance. Methods : This was a single-center cohort study of women newly diagnosed between January 2008 and June 2012 with low-risk GTN during postmolar surveillance and treated with single-agent methotrexate at Charing Cross Hospital, a UK national center for treatment of gestational trophoblastic disease. Two hundred seventeen women underwent an ultrasound for UAPI measurement prior to initiation of chemotherapy. To examine serologic markers of methotrexate resistance among this cohort, we performed a case-control study using archived serum from 76 patients who could be matched based on prognostic risk score. Serum samples were examined by immunoassay to measure 8 different angiogenic factors (VEGF-A, FGF-basic, PLGF-1, PDGF-BB, EGF, ANGPT2, BMP-9, and ENG). Receiver-operator characteristic area under the curve (AUC) values were calculated for the ability of each analyte to correctly classify patients as methotrexate sensitive (MTX-S) or resistant (MTX-R). Results : Total human chorionic gonadotropin levels were similar between the MTX-S and MTX-R groups. UAPI values were significantly higher in MTX-S (median 1.30 [interquartile range {IQR} = 0.80-1.90]) compared to MTX-R patients (median 0.875 [IQR = 0.60-1.30]; P < 0.0001) with AUC 0.68 (95% confidence interval 0.61-0.76; P < 0.0001). In univariate analysis, only BMP-9 concentrations were significantly different between groups, lower among MTX-S (median of 225 ng/L, IQR = 170-287) compared to MTX-R patients (median 280 ng/L [IQR = 200-339]; P = 0.03). Combining UAPI with BMP-9 concentration improved prediction for chemoresistance with AUC 0.77 (95% confidence interval 0.66-0.88; P < 0.0001). Conclusion : Circulating levels of BMP-9 are elevated in newly diagnosed women with low-risk GTN destined to fail primary methotrexate therapy. A combined test using serum BMP-9 plus UAPI might improve prediction of MTX-R in low-risk GTN. [ABSTRACT FROM AUTHOR]