Pregnancy Zone Protein Serves as a Prognostic Marker and Favors Immune Infiltration in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is a public enemy with a very high incidence and mortality rate, for which there is no specific detectable biomarker. Pregnancy zone protein (PZP) is an immune-related protein; however, the functions of PZP in LUAD are unclear. In this study, a series of bioinformatics methods, combined with immunohistochemistry (IHC), four-color multiplex fluorescence immunohistochemistry (mIHC), quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), were utilized to explore the prognostic value and potential role of PZP in LUAD. Our data revealed that PZP expression was markedly reduced in LUAD tissues, tightly correlated with clinical stage and could be an independent unfavorable prognostic factor. In addition, pathway analysis revealed that high expression of PZP in LUAD was mainly involved in immune-related molecules. Tumor immune infiltration analysis by CIBERSORT showed a significant correlation between PZP expression and several immune cell infiltrations, and IHC further confirmed a positive correlation with CD4+ T-cell infiltration and a negative correlation with CD68+ M0 macrophage infiltration. Furthermore, mIHC demonstrated that PZP expression gave rise to an increase in CD86+ M1 macrophages and a decrease in CD206+ M2 macrophages. Therefore, PZP can be used as a new biomarker for the prediction of prognosis and may be a promising immune-related molecular target for LUAD.

First-line treatment options for advanced non-small cell lung cancer patients with PD-L1 ≥ 50%: a systematic review and network meta-analysis.

INTRODUCTION: Single-agent immune checkpoint inhibitors (ICIs) like pembrolizumab or atezolizumab have been approved as first-line monotherapy for advanced non-small cell lung cancer (NSCLC) patients with PD-L1 ≥ 50%. However, emerging evidences have showed that ICI combinations (chemoimmunotherapy or dual-agent ICIs) argue to offer a higher response rate. In this network meta-analysis, we aimed to evaluate the efficacy and toxicity of first-line single-agent ICIs versus ICI combinations for advanced NSCLC patients with PD-L1 ≥ 50%. METHODS: PubMed, Embase, Cochrane Library and the Clinicaltrials.gov were systematically searched to extract eligible literature until December 2020. Outcomes included overall survival (OS), progression free survival (PFS), objective response rate (ORR) and treatment related adverse events (TRAEs) of grades 3-5. RESULTS: Fourteen studies with 3448 patients were included. The results showed that chemotherapy plus ICIs significantly improved PFS and ORR compared to chemotherapy, and sinti-chemo (HR: 0.31, 95% CI: 0.20-0.49) and pembro-chemo (OR: 4.2, 95% CI: 2.6-6.7) ranked first. In terms of OS, cemiplimab provided the best benefit versus chemotherapy (HR: 0.57, 95% CI: 0.43-0.77), followed by atezolizumab and pembro-chemo. In the subgroup analysis of histological type, pembro-chemo and sinti-chemo showed the best benefit of PFS in squamous and nonsquamous NSCLC, respectively, while there was no significant difference between ICI combinations with single-agent ICIs in OS. Moreover, the addition of chemotherapy to ICIs elevated toxicity compared to chemotherapy. CONCLUSION: The study suggested that chemotherapy plus ICIs might improve PFS and ORR than single-agent ICIs for advanced NSCLC patients with PD-L1 ≥ 50%. However, it did not lead to OS benefit.

The potential prognostic values of the ADAMTS-like protein family: an integrative pan-cancer analysis.

BACKGROUND: A disintegrin-like and metalloproteinase domain with thrombospondin type 1 motifs (ADAMTS)-like proteins, including ADAMTSL1-6 and papilin, which are part of the mammalian ADAMTS superfamily, appear to be relevant to extracellular matrix function and the regulation of ADAMTS protease activity. Their roles in tumor initiation and progression and regulating the tumor microenvironment (TME) are now recognized. METHODS: In the present study, a comprehensive investigation of the pan-cancer effects of ADAMTSLs and their associations with patient survival, drug responses, and the TME was performed by integrating The Cancer Genome Atlas (TCGA) data and annotated data resources. RESULTS: The expression of ADAMTSL family members was found to be dysregulated in many cancer types. More importantly, their expression was frequently associated with patients' overall survival (OS), drug responses, and the TME. ADAMTSL1, ADAMTSL4, and ADAMTSL5 were primarily associated with aggressive phenotypes, while PAPLN was more frequently associated with a favorable prognosis. In a non-small cell lung cancer (NSCLC) cohort, Thrombospondin Type 1 Domain Containing 4 (THSD4) (ADAMTSL6) and Papilin (PAPLN) were associated with immune checkpoint inhibitor (ICI) sensitivity in samples from the Gene Expression Omnibus repository (GSE135222). Twenty and 30 proteins related to THSD4 and PAPLN, respectively, were identified through a proteomic analysis of 18 Chinese lung adenocarcinoma patients. CONCLUSIONS: Our findings extend understandings of the role of the ADAMTSL family in cancers and are a valuable resource on their clinical utility. This article provides insight into the clinical importance of next-generation sequencing technology to identify novel biomarkers for prognosis and investigate therapeutic strategy for clinical benefit.

The transcription factor RUNX2 fuels YAP1 signaling and gastric cancer tumorigenesis.

Despite considerable efforts in the detection and treatment of gastric cancer (GC), the underlying mechanism of the progression of GC remains unknown. Our previous work has demonstrated the remarkable role of Runt-related transcription factor 2 (RUNX2), in fueling the invasion and metastasis of GC. The present study aimed to elucidate the role of RUNX2 in tumorigenesis of GC. We assessed Runx2 expression and its clinical significance via bioinformatic analysis of the Cancer Genome Atlas and Gene Expression Omnibus databases. Roles for Runx2 in self-renewal and tumorigenesis were examined in vitro and in vivo. Further bioinformatic analysis was applied to study the mechanism of GC progression. We found that Runx2 was highly expressed in the early stage of GC and positively correlated with a poor clinical outcome of patients. Runx2 was also significantly correlated with clinicopathological features, such as Hp infection, new neoplastic events, primary therapeutic outcome, ethnicity, race, and tumor stage. Multivariate analysis revealed that together with Runx2, age, cancer status, M stage, and T stage were independent prognostic factors for the outcome of GC patients. RUNX2 overexpression induced increased anchorage-independent colony formation, sphere formation, and tumorigenesis in GC cells in vitro and in vivo. Mechanistically, bioinformatic analysis indicated that yes1 associated transcriptional regulator (YAP1) might be a downstream target of RUNX2. Specific knockdown of YAP1 reduced the tumor-initiating ability of GC cells induced by ectopic Runx2 expression. Our findings support the hypothesis that RUNX2 exerts oncogenic properties via YAP1 regulation, highlighting essential roles for RUNX2 and YAP1 in gastric carcinogenesis and suggesting potential therapeutic targets.

MicroRNAs in the Occurrence and Development of Primary Hepatocellular Carcinoma.

Hepatocellular carcinoma is one of the deadliest types of cancer. Despite improvements in treatment over the past few decades, patient survival remains poor and there is an urgent need for development of targeted therapies. MicroRNAs represent a class of small RNAs, frequently deregulated in human malignancies. We are reviewing the role of microRNA in the development of primary hepatocellular carcinoma and its use as a biomarker for early diagnosis and clinical treatment. First, we describe the current incidence and possible causes of the incidence of hepatocellular carcinoma, followed by the introduction of microRNA synthesis, maturation and function, and finally we explain the role of microRNA in the development of hepatocellular carcinoma and its clinical value as a biological marker in the diagnosis and treatment of liver cancer. A comprehensive analysis of cellular microRNA is a benefit for early diagnosis of hepatocellular carcinoma and early clinical intervention, and microRNA is considered by some to be a key target of gene therapy to control the occurrence and development of hepatocellular carcinoma..