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Simple Summary: Pancreatic cancer remains as one of the most life-threatening cancers with a 5-year overall survival rate less than 6%. As a transmembrane protein, capillary formation gene 2 (CMG2) mediates cell–matrix adhesion and migration. Recent studies have revealed emerging roles of CMG2 in various cancers. This study aimed to evaluate expression of CMG2 in pancreatic cancer and its implication in the disease progression and distant metastasis. Interestingly, the significant upregulation of CMG2 was seen in pancreatic cancer, which was associated with poor survival and distant metastases highlighting the potential of targeting this molecule for the prevention of dissemination of pancreatic cancer cells. Capillary morphogenesis gene 2 (CMG2) mediates cell–matrix interactions to facilitate cell adhesion and migration. CMG2 has been implicated in the disease progression of breast cancer, prostate cancer and gastric cancer. The present study aims to determine the role of CMG2 in the disease progression and peritoneal metastasis of pancreatic cancer. Pancreatic tumour samples were collected from Peking University Cancer Hospital. CMG2 expression was determined using quantitative PCR. After the creation of knockdown and overexpression of CMG2 in pancreatic cancer cells, the effect of CMG2 on several cell functions and adhesion to the peritoneum was examined. Potential pathways regulated by CMG2 were found via proteomics analysis and drug tests. CMG2 was upregulated in pancreatic cancer tissues and associated with a poor prognosis. CMG2 was increased in metastatic lesions and those primary tumours with distant metastases. CMG2 promotes cell–cell, cell–matrix and cell–hyaluronic acid adhesion, which may be mediated by epidermal growth factor receptor (EGFR) and focal adhesion kinase (FAK) pathway activation. [ABSTRACT FROM AUTHOR]

Simple Summary: Hyaluronic acid (HA) is a kind of polysaccharide that widely exists in tissues of vertebrates, functioning as a lubricator, an adhesion-reducing molecule, and an extracellular matrix (ECM) organiser. The function of HA depends on its relative molecular mass. High molecular weight HA (HMW-HA) helps to maintain tissue homeostasis, and can be degraded to elicit pro-inflammatory, angiogenic, and tumour microenvironment (TME) remodelling effects. HA accumulation was found to be linked to cancer progression and worse patient outcomes. The term hyaluronic acid-interacting molecule (HAIM) refers to a group of proteins that can interact with HA and participate in the regulation of cancer cells and immune cell behaviour. Membrane-anchored HAIMs bind to HA as receptors to regulate cellular function through various pathways, while secreted HAIMs bind with HA as a scaffold to construct ECM and can also act on a variety of cells in the TME to coordinate release and actions of cytokines and enzymes to reshape the ECM. Some of these molecules also play a role in HA transport, endocytosis, and degradation. Understanding these complex and profound interactions between HAIMs and HA will shed light on their role in the TME to foster a supportive microenvironment for local invasive expansion and distant spread of cancer cells. Hyaluronic acid (HA) is a prominent component of the extracellular matrix, and its interactions with HA-interacting molecules (HAIMs) play a critical role in cancer development and disease progression. This review explores the multifaceted role of HAIMs in the context of cancer, focusing on their influence on disease progression by dissecting relevant cellular and molecular mechanisms in tumour cells and the tumour microenvironment. Cancer progression can be profoundly affected by the interactions between HA and HAIMs. They modulate critical processes such as cell adhesion, migration, invasion, and proliferation. The TME serves as a dynamic platform in which HAIMs contribute to the formation of a unique niche. The resulting changes in HA composition profoundly influence the biophysical properties of the TME. These modifications in the TME, in conjunction with HAIMs, impact angiogenesis, immune cell recruitment, and immune evasion. Therefore, understanding the intricate interplay between HAIMs and HA within the cancer context is essential for developing novel therapeutic strategies. Targeting these interactions offers promising avenues for cancer treatment, as they hold the potential to disrupt critical aspects of disease progression and the TME. Further research in this field is imperative for advancing our knowledge and the treatment of cancer. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the distant metastatic patterns and prognostic factors for overall survival (OS) and cancer‐specific survival (CSS) in de novo metastatic nasopharyngeal carcinoma (mNPC) using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Patients with de novo mNPC who had been diagnosed between 2004 and 2016 were identified from the SEER database. Kaplan–Meier analysis was used to calculate OS and CSS. Log‐rank tests were employed to measure survival variation among subgroups. Individual predictors of CSS and OS were examined using Cox proportional‐hazards regression models in patients with de novo mNPC. Results: We evaluated 224 patients with de novo mNPC who matched our inclusion criteria. Three‐year CSS and OS for the whole cohort was 29.8% and 27.9%, respectively. Univariate analysis indicated that CSS and OS were influenced by age, histology, radiotherapy, chemotherapy, and liver metastasis. Neither the number of metastatic sites nor their specific location in bone, lungs, distant lymph nodes or brain significantly affected CSS or OS. The aforementioned independent prognosticators continued to significantly influence survival following multivariate analysis. Taking distant metastasis without liver involvement as a reference, liver metastasis was associated significantly with shorter OS at a hazard ratio (HR) of 1.581 (P =.021) and CSS at a HR of 1.643 (P =.016). Older age, keratinizing squamous cell carcinoma, no chemotherapy, and no radiotherapy were also prognosticators for poor OS (P <.05). Similar results were documented for CSS (P <.05). Conclusion: For patients with de novo mNPC, liver metastasis is an independent prognosticator for inferior CSS and OS. Level of Evidence: 3a Laryngoscope, 131:E1130–E1138, 2021 [ABSTRACT FROM AUTHOR]

Mutation of p110 alpha-catalytic subunit of phosphatidylinositol 3-kinase (PIK3CA) has high predictive and prognostic values for breast cancer. Hence, there has been a marked interest in detecting and monitoring PIK3CA genotype with non-invasive technique, such as circulating free DNA (cfDNA). However, the diagnostic accuracy of PIK3CA genotyping by cfDNA is still a problem of controversy. Here, we conducted the first meta-analysis to evaluate overall diagnostic performance of cfDNA for PIK3CA mutation detection. Literature search was performed in Pubmed, Embase and Cochrane Central Register of Controlled Trials databases. Seven cohorts from five studies with 247 patients were included. The pooled sensitivity, specificity, positive and negative likelihood ratio, diagnostic odds ratio and area under summary receiver operating characteristic curve were calculated for accuracy evaluation. The pooled sensitivity and specificity were 0.86 (95% confidence interval [CI] 0.32–0.99) and 0.98 (95% CI 0.86–1.00), respectively; the pooled positive and negative likelihood ratio were 42.8 (95% CI 5.1–356.9) and 0.14 (95% CI 0.02–1.34), respectively; diagnostic odds ratio for evaluating the overall diagnostic performance was 300 (95% CI 8–11867); area under summary receiver operating characteristic curve reached 0.99 (95% CI 0.97–0.99). Subgroup analysis with metastatic breast cancer revealed remarkable improvement in diagnostic performance (sensitivity: 0.86–0.91; specificity: 0.98; diagnostic odds ratio: 300–428). This meta-analysis proved that detecting PIK3CA gene mutation by cfDNA has high diagnostic accuracy in breast cancer, especially for metastatic breast cancer. It may serve as a reliable non-invasive assay for detecting and monitoring PIK3CA mutation status in order to deliver personalized and precise treatment. [ABSTRACT FROM AUTHOR]

To verify whether omitting radiotherapy from breast cancer treatment for patients ≥ 70 years old following breast-conserving surgery (BCS) without axillary lymph node dissection is safe. Previous studies have shown that omitting breast radiotherapy after BCS and axillary lymph node dissection is safe for elderly breast cancer patients. We aimed to evaluate the safety of BCS without axillary surgery or breast radiotherapy (BCSNR) in elderly patients with breast cancer and clinically negative axillary lymph nodes. We performed a retrospective analysis of 481 patients with breast cancer, aged ≥ 70 years, between 2010 and 2016. Of these, 302 patients underwent BCSNR and 179 underwent other, larger scope operations. Local recurrence rate, ipsilateral breast tumor recurrence (IBTR) rate, distant metastasis rate, breast-related death, disease-free survival (DFS), and overall survival (OS) were compared between the two groups. After a median follow-up of 60 months, no significant differences in local recurrence, distant metastasis rate, breast-related death, and DFS were noted. The OS was similar (P = 0.56) between the BCSNR group (91.7%) and other operations group (93.0%). The IBTR rate was considered low in both groups, however resulted greater (P = 0.005) in the BCSNR group (5.3%) than in other operations group (1.6%). BCSNR did not affect the survival of elderly patients with breast cancer with clinically negative axillary lymph nodes. IBTR was infrequent in both groups; however, there was a significant difference between the two groups. BCSNR is a feasible treatment modality for patients with breast cancer ≥ 70 years old with clinically negative axillary lymph nodes. [ABSTRACT FROM AUTHOR]