REG3A overexpression functions as a negative predictive and prognostic biomarker in rectal cancer patients receiving CCRT.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is suggested before resection surgery in the control of rectal cancer. Unfortunately, treatment outcomes are widely variable and highly patient-specific. Notably, rectal cancer patients with distant metastasis generally have a much lower survival rate. Accordingly, a better understanding of the genetic background of patient cohorts can aid in predicting CCRT efficacy and clinical outcomes for rectal cancer before distant metastasis. METHODS: A published transcriptome dataset (GSE35452) (n=46) was utilized to distinguish prospective genes concerning the response to CCRT. We recruited 172 rectal cancer patients, and the samples were collected during surgical resection after CCRT. Immunohistochemical (IHC) staining was performed to evaluate the expression level of regenerating family member 3 alpha (REG3A). Pearson's chi-squared test appraised the relevance of REG3A protein expression to clinicopathological parameters. The Kaplan-Meier method was utilized to generate survival curves, and the log-rank test was performed to compare the survival distributions between two given groups. RESULTS: Employing a transcriptome dataset (GSE35452) and focusing on the inflammatory response (GO: 0006954), we recognized that REG3A is the most significantly upregulated gene among CCRT nonresponders (log2 ratio=1.2472, p=0.0079). Following IHC validation, high immunoexpression of REG3A was considerably linked to advanced post-CCRT tumor status (p<0.001), post-CCRT lymph node metastasis (p=0.042), vascular invasion (p=0.028), and low-grade tumor regression (p=0.009). In the multivariate analysis, high immunoexpression of REG3A was independently correlated with poor disease-specific survival (DSS) (p=0.004) and metastasis-free survival (MeFS) (p=0.045). The results of the bioinformatic analysis also supported the idea that REG3A overexpression is implicated in rectal carcinogenesis. CONCLUSION: In the current study, we demonstrated that REG3A overexpression is correlated with poor CCRT effectiveness and inferior patient survival in rectal cancer. The predictive and prognostic utility of REG3A expression may direct patient stratification and decision-making more accurately for those patients.

Synthetic autophagy receptor.

Macroautophagy/autophagy receptors target their substrates to phagophores for subsequent sequestration within autophagosomes. During phagophore membrane expansion in mammalian cells, autophagy receptors simultaneously interact with the ubiquitinated substrates and the LC3/GABARAP proteins on the expanding membrane. In this punctum, we summarize and discuss our recent research progress on synthetic autophagy receptors (AceTACs). The series of AceTACs were designed by engineering the essential interacting domains and motifs of SQSTM1/p62 (sequestosome 1), a major mammalian autophagy receptor. Particularly, we replaced the ubiquitin-associated domain of SQSTM1 with a target-specific antibody, redirecting the bifunctional interactions of wild-type SQSTM1 and directing the degradation target into the autophagy process. We successfully demonstrated the targeted degradation of aggregation-prone proteins using the AceTAC degraders. Moreover, we presented a model system with a guideline to induce targeted degradation of organelles through the autophagy machinery.

Ubiquitin-conjugating enzyme E2C (UBE2C) is a prognostic indicator for cholangiocarcinoma.

Cholangiocarcinoma is the most common malignant bile duct tumor in Southeast Asia. The special location of cholangiocarcinoma leads to it being difficult to diagnose. Currently, the progress in clinical prognosis outcomes remains abysmal owing to the lack of definitive diagnostic criteria. Therefore, uncovering the potential markers for cholangiocarcinoma is a pressing issue. Ubiquitin-conjugating enzyme E2 C (UBE2C) is a critical ubiquitination enzyme; it is involved in the tumorigenesis of various malignancies and affects the patient's prognosis. However, there is currently no relevant literature to indicate whether UBE2C is related to the clinical survival outcome of cholangiocarcinoma patients. In this report, we mined the published cholangiocarcinoma transcriptome data set (GSE26566), compared it with the ubiquitination-associated gene (GO:0016567), and identified that UBE2C was highly expressed in cholangiocarcinoma tumor tissue. Moreover, high expression of UBE2C was markedly correlated with surgical margin, primary tumor, histological variants, and histological grade. More specifically, high expression of UBE2C was negatively associated with overall survival, disease-specific survival, local recurrence-free survival, and metastasis-free survival in patients with cholangiocarcinoma. Our findings demonstrate that UBE2C may provide a potential therapeutic marker and prognostic factor for cholangiocarcinoma patients.

LAMC2 is a potential prognostic biomarker for cholangiocarcinoma.

Cholangiocarcinoma is a common malignancy with increasing incidence worldwide. Most patients are diagnosed at the advanced stage with poor survival rate. Laminin subunit γ2 (LAMC2) is a heparin binding-associated gene involved in tumorigenesis and has been implicated in the prognosis of various types of cancers. However, it is unclear whether expression of LAMC2 is associated with the clinical outcome of patients with cholangiocarcinoma. In the present study, the role and prognostic value of LAMC2 expression in patients with cholangiocarcinoma was investigated. Clinical information and pathological characteristics were analyzed and the association between LAMC2 expression and clinical characteristics, pathological findings and patient outcomes, including metastasis-free and disease-specific survival, were investigated. Data from 182 patients with cholangiocarcinoma were evaluated. High LAMC2 expression was associated with higher tumor stage (P<0.001), large duct type (P=0.024) and poor histological grade (P=0.002). Kaplan-Meier analysis showed high LAMC2 expression was associated with lower overall (P=0.003), disease-specific (P=0.0025), local recurrence-free (P<0.0001) and metastasis-free survival (P<0.0001). Moreover, multivariate analysis demonstrated that increased LAMC2 expression was a significant predictive risk factor for overall [hazard ratio (HR) 1.713; P=0.034], disease-specific (HR 2.011; P=0.039), local recurrence-free (HR 2.721; P<0.001) and metastasis-free survival (HR 3.117; P<0.001). Gene enrichment analysis using Gene Ontology showed that terms associated with LAMC2 upregulation were 'regulation of platelet-derived growth factor receptor-ßsignaling pathway' and 'platelet-derived growth factor receptor-ß signaling pathway'. The present study indicated that LAMC2 was upregulated in cholangiocarcinoma tumor tissue and had an inverse association with overall, disease-specific, local recurrence-free and metastasis-free survival in patients with cholangiocarcinoma. These results suggested that LAMC2 may serve as a potential biomarker for cholangiocarcinoma.

Nutritional deficiency anemia and post-acute sequelae in patients with severe acute respiratory syndrome coronavirus 2 infection: A six-month retrospective cohort analysis of 30 892 patients.

The effect of anemia on the post-acute outcome of patients with severe acute respiratory syndrome coronavirus 2 infection was unclear. This study aimed to investigate the potential association between nutritional deficiency anemia (NDA) status and post-acute sequelae of patients with SARS-CoV-2 infection. This retrospective cohort study included patients with coronavirus disease (COVID-19) from January 1, 2022 to November 30, 2022 using the TriNetX research network. The patients were grouped into the NDA group comprising patients diagnosed with NDA and the control group comprising patients without NDA, and propensity score matching (PSM) was performed to balance the two groups. The primary outcome was a composite of post-COVID-19 condition, all-cause hospitalization, and all-cause death. The secondary outcomes were any individual outcomes of the primary composite. The follow-up period was set at 90-180 days after COVID-19 diagnosis. Two cohorts comprising 15 446 nonhospitalized patients with COVID-19 in each group with balanced baseline characteristics were created using PSM. During the follow-up period, the NDA group demonstrated a higher risk of the composite primary outcome, including post-COVID-19 condition, all-cause hospitalization, or all-cause death (hazard ratio [HR], 1.896; 95% confidence interval [CI] = 1.757-2.045). Regarding secondary outcomes, the NDA group was associated with worse outcomes, including post-COVID-19 condition (HR, 1.992; 95% CI = 1.403-2.828), all-cause hospitalization (HR, 1.856; 95% CI = 1.714-2.009), and all-cause death (HR, 3.922; 95% CI = 2.910-5.285) compared to the control group. Among nonhospitalized patients with COVID-19, NDA was associated with a higher risk of post-COVID-19 condition, all-cause hospitalization, and all-cause death during the 90-180-day follow-up period.

Cartilage oligomeric matrix protein overexpression is an independent poor prognostic indicator in patients with intrahepatic cholangiocarcinoma.

Cartilage oligomeric matrix protein (COMP) interacts with various extracellular matrix proteins in tissues. Elevated COMP levels recently linked to worse overall survival in multiple cancer types. COMP's significance in intrahepatic cholangiocarcinoma (iCCA) remains uncertain. Here we report a retrospective study to explore COMP's impact on iCCA outcomes. We collected 182 patients' iCCA tumor tissues. COMP overexpression was associated with adverse factors like R1 resection (p = 0.008), advanced T stage (p < 0.001), large duct type (p = 0.004), and poorly differentiated histology (p = 0.002). COMP overexpression correlates with poorer DFS (HR, 3.651; p = 0.001), OS (HR, 1.827; p = 0.023), LRFS (HR, 4.077; p < 0.001), and MFS (HR, 3.718; p < 0.001). High COMP expression ties to worse overall survival (p = 0.0001), DSS (p < 0.0001), LRFS (p < 0.0001), and MFS (p < 0.0001). In conclusion, COMP overexpression links to poor prognosis and pathological features in iCCA, indicating its potential as a biomarker.

Autophagy Receptor-Inspired Antibody-Fusion Proteins for Targeted Intracellular Degradation.

Autophagy is responsible for the degradation of large intracellular contents, such as unwanted protein aggregates and organelles. Impaired autophagy can therefore lead to the accumulation of pathological aggregates, correlating with aging and neurodegenerative diseases. However, a broadly applicable methodology is not available for the targeted degradation of protein aggregates or organelles in mammalian cells. Herein, we developed a series of autophagy receptor-inspired targeting chimeras (AceTACs) that can induce the targeted degradation of aggregation-prone proteins and protein aggregates (e.g., huntingtin, TDP-43, and FUS mutants), as well as organelles (e.g., mitochondria, peroxisomes, and endoplasmic reticulum). These antibody-fusion-based AceTAC degraders were designed to mimic the function of autophagy receptors, simultaneously binding with the cellular targets and the LC3 proteins on the autophagosomal membrane, eventually transporting the target to the autophagy-lysosomal process for degradation. The AceTAC degradation system provides design principles for antibody-based degradation through autophagy, largely expanding the scope of intracellular targeted degradation technologies.

Lymphocyte-Rich Hepatocellular Carcinoma with Multiple Lymphadenopathy and Positive Epstein-Barr Virus Encoding Region.

Lymphocyte-rich hepatocellular carcinoma (HCC) represents the rarest subtype among the various subgroups of HCC, and limited clinical data are available for this particular subtype. It is commonly observed as a solitary lesion and tends to present at an early stage. Histopathological examination typically reveals tumor cells infiltrated by a lymphocyte-rich background, leading to its designation as lymphoepithelioma-like HCC. Unlike other lymphoepithelioma-like tumors associated with the Epstein-Barr virus (EBV), lymphocyte-rich HCC is predominantly negative for EBV. This subtype is characterized by more favorable clinical outcomes and prognosis compared to conventional HCC. Here, we present a case of lymphocyte-rich hepatocellular carcinoma (HCC) characterized by the presence of bilateral hepatic tumors and concurrent multiple lymphadenopathy. Interestingly, contrary to previous literature, the examination for the Epstein-Barr virus (EBV) revealed a positive result in this particular case.

SYNPO2 upregulation is an unfavorable prognostic factor for nasopharyngeal carcinoma patients.

Nasopharyngeal carcinoma (NPC) is the most common malignant neoplasm of the nasopharynx. Despite improvements in the clinical treatment strategies for NPC, NPC patients usually have poor survival rates because of late diagnosis, tumor metastasis, and recurrence. Therefore, the identification of potential diagnostic and prognostic markers for NPC is imperative. We investigated the differential expression of cell adhesion-related genes (gene ontology:0003779) and tumorigenesis-related genes (GSE12452) in patients with NPC. The correlations between synaptopodin-2 (SYNPO2) immune expression and clinicopathological features were analyzed using Pearson chi-square test. Multivariate analysis was performed using Cox proportional hazards model. SYNPO2 expression was significantly higher in NPC tumor tissues than in nontumor tissues. High SYNPO2 expression was significantly associated with the advanced disease stage (P = .006). Univariate analysis showed that high expression of SYNPO2 was associated with poor disease-specific survival, distal metastasis-free survival, and local recurrence-free survival in patients with NPC. Notably, our multivariate analysis demonstrated that high SYNPO2 expression was substantially correlated with inferior disease-specific survival (hazard ratio = 1.968, P = .012) and local recurrence-free survival (hazard ratio = 3.386, P = .001). Overall, our findings reveal that SYNPO2 may aid in the development of potential prognostic biomarkers for NPC patients.

Upregulation of dihydropyrimidinase-like 3 (DPYSL3) protein predicts poor prognosis in urothelial carcinoma.

BACKGROUND: Dihydropyrimidinase-like 3 (DPYSL3) is a cytosolic phosphoprotein expressed in the nervous system and is crucial for neurogenesis. A previous study showed that increased DPYSL3 expression promotes tumour aggressiveness in pancreatic ductal adenocarcinoma, gastric cancer, and colon cancer. However, the role of DPYSL3 in affecting the biological behaviour of urothelial carcinoma (UC) is not yet understood. METHODS: A UC transcriptomic dataset from the Gene Expression Omnibus and the Urothelial Bladder Cancer (BLCA) dataset from The Cancer Genome Atlas were used for the in silico study. We collected 340 upper urinary tract urothelial carcinoma (UTUC) and 295 urinary bladder urothelial carcinoma (UBUC) samples for the immunohistochemical study. Fresh tumour tissue from 50 patients was used to examine the DPYSL3 mRNA level. In addition, urothelial cell lines with and without DPYSL3 knockdown were used for the functional study. RESULTS: The in silico study revealed that DPYSL3 correlated with advanced tumour stage and metastasis development while functioning primarily in the nucleobase-containing compound metabolic process (GO:0006139). DPYSL3 mRNA expression is significantly upregulated in advanced UC. Furthermore, overexpression of the DPYSL3 protein is significantly associated with the aggressive behaviour of UTUC and UBUC. DPYSL3 expression independently predicts disease-specific survival (DSS) and metastatic-free survival (MFS) in patients with UC. In non-muscle-invasive UBUC, DPYSL3 expression predicts local recurrence-free survival. UC cell lines with DPYSL3 knockdown exhibited decreased proliferation, migration, invasion, and human umbilical vein endothelial cells (HUVECs) tube formation but increased apoptosis and G1 arrest. Gene ontology enrichment analysis revealed that the enriched processes related to DPYSL3 overexpression in UC were tissue morphogenesis, cell mesenchyme migration, smooth muscle regulation, metabolic processes, and RNA processing. In vivo study revealed DPYSL3 knockdown in UC tumours significantly suppressed the growth of tumours and decreased MYC and GLUT1 protein expression. CONCLUSIONS: DPYSL3 promotes the aggressiveness of UC cells by changing their biological behaviours and is likely associated with cytoskeletal and metabolic process modifications. Furthermore, DPYSL3 protein overexpression in UC was associated with aggressive clinicopathological characteristics and independently predicted poor clinical outcomes. Therefore, DPYSL3 can be used as a novel therapeutic target for UC.

Cardiovascular Event Recurrence and Costs after First Myocardial Infarction, Ischemic Stroke, or Intracerebral Hemorrhage in Taiwan.

Background/Objectives: We aimed to assess the incidence of recurrent cardiovascular (CV) events after the first myocardial infarction (MI), ischemic stroke (IS), or intracerebral hemorrhage (ICH) and to estimate acute and follow-up medical costs. Methods: Using Taiwan's National Health Insurance Research Database, we identified patients with their first MI, IS, or ICH between 2011 and 2017. The cumulative incidence rates of second CV events (including events of the same type [recurrent] or of the other two types) were estimated. The costs for hospitalization and all-cause follow-up were calculated for the first and recurrent CV events and are presented as median (Q1~Q3) in 2017 US dollars. Results: We identified 70,428 patients with a first MI, 123,857 with a first IS, and 41,347 with a first ICH. The cumulative incidence rates of recurrence during the first year and after six years were 3.9% and 10.1% for MI, 5.3% and 13.8% for IS, and 3.9% and 8.9% for ICH, respectively. For first and recurrent nonfatal events, acute hospitalization costs were $4,729 (3,737~5,985) and $4,459 (2,887~6,026) for MI; $1,136 (756~2,183) and $1,224 (774~2,412) for IS; and $2,985 (1,264~8,831) and $2,170 (1,183~4,675) for ICH, respectively. Total annual costs for nonfatal first events in the first year and second year of follow-up were $2413 (1,393~6,120) and $1,293 (654~2,868) for MI, $2,174 (1,040~5,472) and $1,394 (602~3,265) for IS, and $2,963 (995~8,352) and $1,185 (405~3,937) for ICH, respectively. Conclusions: In patients with a first MI, IS, and ICH, recurrent CV events continue to substantially impact public health and escalate the economic burden.

Case report: Heterogenous SMARCA4-deficient thoracic non-small cell lung carcinoma with various responses to nivolumab.

SMARCA4-deficient non-small cell carcinoma is an aggressive neoplasm with poor outcome. Several studies have highlighted its immunochemistry, pathophysiology, and underlying mechanisms, but studies of its definite treatment are few. Here, we report on a 69-year-old male with heterogenous pathological presentations of SMARCA4-deficient non-small cell carcinoma. He initially presented with neck lymphadenopathies. Immunohistochemistry staining and genomic profiling confirmed the diagnosis of SMARCA4-deficient non-small cell carcinoma. The patient responded well to immune checkpoint inhibitors with nivolumab. However, new lesions with various pathological presentations and various responses to nivolumab appeared during the treatment course. The patient survived more than 3 years from the initial diagnosis. This case shows the efficacy of nivolumab to treat SMARCA4-deficient non-small cell lung carcinoma.

Prognostic Significance of DNA Topoisomerase II Alpha (TOP2A) in Cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CCA) is a malignant tumor with an increasing incidence worldwide. Although radiation therapy has improved the therapeutic efficiency of CCA treatment, differential expression of genes among cholangiocarcinoma subtypes has been revealed through precise sequencing. However, no specific molecular therapeutic targets or biomarkers have been figured out for use in precision medicine, and the exact mechanism by which antitumorigenic effects occur is still unclear. Therefore, it is necessary to conduct further studies on the development and mechanisms associated with CCA. METHODS: We examined the clinical data and pathological features of patients with cholangiocarcinomas. We investigated the associations between DNA Topoisomerase II Alpha (TOP2A) expression and patient outcomes, such as metastasis-free survival (MFS) and disease-specific survival (DSS), as well as clinical characteristics and pathological results. RESULTS: TOP2A expression was shown to be upregulated in CCA tissue sections by immunohistochemistry staining and data mining. Moreover, we observed that the TOP2A expression correlated with clinical features, such as the primary tumor stage, histological variants, and patients with hepatitis. Furthermore, high expression of TOP2A was associated with worse survival outcomes in terms of the overall survival (p < 0.0001), disease-specific survival (p < 0.0001), and metastasis-free survival (p < 0.0001) compared with patients in the low TOP2A expression group. This indicates that a high level of TOP2A expression is related to an unfavorable prognosis. CONCLUSIONS: Our results show that TOP2A is highly expressed in CCA tissues, and its upregulation is correlated with the primary disease stage and poor prognosis significantly. Consequently, TOP2A is a prognostic biomarker and a novel therapeutic target for the treatment of CCA.

Co-contaminants of ethinylestradiol and sulfamethoxazole in groundwater exacerbate ecotoxicity and ecological risk and compromise the energy budget of C. elegans.

Ethinylestradiol (EE2) and sulfamethoxazole (SMX) are among pharmaceuticals and personal care products (PPCPs) and regarded as emerging contaminants in groundwater worldwide. However, the ecotoxicity and potential risk of these co-contaminants remain unknown. We investigated the effects of early-life long-term co-exposure to EE2 and SMX in groundwater on life-history traits of Caenorhabditis elegans and determined potential ecological risks in groundwater. L1 larvae of wild-type N2 C. elegans were exposed to measured concentrations of EE2 (0.001, 0.75, 5.1, 11.8 mg/L) or SMX (0.001, 1, 10, 100 mg/L) or co-exposed to EE2 (0.75 mg/L, no observed adverse effect level derived from its reproductive toxicity) and SMX (0.001, 1, 10, 100 mg/L) in groundwater. Growth and reproduction were monitored on days 0 - 6 of the exposure period. Toxicological data were analyzed using DEBtox modeling to determine the physiological modes of action (pMoAs) and the predicted no-effect concentrations (PNECs) to estimate ecological risks posed by EE2 and SMX in global groundwater. Early-life EE2 exposure significantly inhibited the growth and reproduction of C. elegans, with lowest observed adverse effect levels (LOAELs) of 11.8 and 5.1 mg/L, respectively. SMX exposure impaired the reproductive capacity of C. elegans (LOAEL = 0.001 mg/L). Co-exposure to EE2 and SMX exacerbated ecotoxicity (LOAELs of 1 mg/L SMX for growth, and 0.001 mg/L SMX for reproduction). DEBtox modeling showed that the pMoAs were increased growth and reproduction costs for EE2 and increased reproduction costs for SMX. The derived PNEC falls within the range of detected environmental levels of EE2 and SMX in groundwater worldwide. The pMoAs for EE2 and SMX combined were increased growth and reproduction costs, resulting in lower energy threshold values than single exposure. Based on global groundwater contamination data and energy threshold values, we calculated risk quotients for EE2 (0.1 - 123.0), SMX (0.2 - 91.3), and combination of EE2 and SMX (0.4 - 341.1). Our findings found that co-contamination by EE2 and SMX exacerbates toxicity and ecological risk to non-target organisms, suggesting that the ecotoxicity and ecological risk of co-contaminants of pharmaceuticals should be considered to sustainably manage groundwater and aquatic ecosystems.

Low expression of ZSCAN4 predicts unfavorable outcome in urothelial carcinoma of upper urinary tract and urinary bladder.

BACKGROUND: With the advance in genome-wide analyses, genetic alternations have been found to play an important role in carcinogenesis and aggressiveness of UC. Through bioinformatic analysis of gene expression profiles of urinary bladder urothelial carcinoma (UBUC) from publicly available GEO dataset (GSE31684), Zinc finger and SCAN domain containing 4 (ZSCAN4) was identified as a significant downregulated gene in muscle-invasive bladder cancer when compared with non-muscle-invasive bladder cancer. METHODS: The expression of ZSCAN4 was evaluated by immunohistochemistry in 340 upper urinary tract urothelial carcinomas (UTUCs) and 295 UBUCs. The expression profiles of ZSCAN4 and potential signaling pathways were analyzed bioinformatically. RESULTS: In UTUC, low expression of ZSCAN4 was significantly associated with advanced primary pT stage (P = 0.011), increased nodal metastasis (P = 0.002) and increased vascular invasion (P = 0.019). In UBUC, low expression of ZSCAN4 was significantly correlated with advanced primary pT stage (P < 0.001), increased nodal metastasis (P = 0.001), high histological grade (P = 0.003) and increased vascular invasion (P = 0.003). In survival analysis, low expression of ZSCAN4 acted as an independent negative prognostic factor for disease-specific survival and metastasis-free survival both in UTUC and UBUC. Gene ontology analysis showed that ZSCAN4 mRNA and its co-downregulated genes are associated with the mitotic cell cycle. CONCLUSIONS: Low expression of ZSCAN4 predicted worse outcome in urothelial carcinoma and might have potential regulatory role in cell mitosis.

Assessing the ecological risk and ecotoxicity of the microbially mediated restoration of heavy metal-contaminated river sediment.

Anthropogenic activities such as mining, smelting industries, and the application of pesticides in agriculture might result in contamination of multiple heavy metals in the environment. Heavy metal contamination of sediment is a serious environmental problem, and thus the remediation of contaminated sediment is a worldwide challenge. Several strategies have been developed for the remediation of contaminated sediment, however the ecological risk and ecotoxicity of the restored sediment have rarely been evaluated. We assessed whether river sediment highly contaminated with heavy metals could be restored using microbial bioleaching followed by evaluating the residual toxicity and ecological risk of the microbially remediated sediment. Sequential extraction revealed that the bioavailable levels of Cu, Ni, and Zn in the contaminated sediment exceeded sediment quality guideline (SQG) thresholds. It was consequently found that acidophilic sulfur-oxidizing Acidicaldus sp. SV5 effectively bioleached Cu, Ni, and Zn from the contaminated sediment, reducing the bioavailable fraction of these elements below SQG thresholds. The ecological risk assessment indicated that SV5-driven remediation significantly reduced the potential ecological risk of the contaminated sediment. The residual ecotoxicity of the microbially remediated sediment was also tested with the soil nematode Caenorhabditis elegans. There was a significant decrease in the body burden of Cu, Ni, and Zn in C. elegans and a reduction in the toxicological effect on survival, growth, and reproduction in the microbially remediated sediment. Our study suggests that a combination of chemical analysis, chemical-based ecological risk assessment, and ecotoxicity tests would be helpful for the development of efficient and eco-friendly strategies for the restoration of contaminated sediment, which could be incorporated into sediment quality management practices.

No survival benefit from adding chemotherapy to adjuvant radiation in advanced major salivary gland cancer.

This study aimed to compare survival of patients with advanced major salivary gland cancers treated with adjuvant chemoradiation therapy (CRT) versus radiotherapy (RT) alone, after surgical resection. The Taiwan Cancer Registry database was used to identify patients (2009-2017) with advanced (T3-4 or nodal positivity) major salivary gland cancers, treated post-surgically with adjuvant CRT or RT alone. Overall survival (OS) and disease-specific survival (DSS) evaluated using Kaplan-Meier. Stratified analyses conducted on clinicopathological features. A total of 395 patients were analyzed: 178 (45.1%) received adjuvant CRT; 217 (54.9%) received adjuvant RT alone. Median radiation dose was 66 Gy in 33 fractions. Cisplatin was most common chemotherapy regimen. After a median follow-up of 3.37 years, there was no significant difference in OS or DSS (p = 0.1354 and 0.3361, respectively) between groups. Adding chemotherapy to adjuvant RT was not significantly associated with improved OS (adjusted hazard ratio [aHR] 0.94; 95% CI 0.72-1.23) and DSS (aHR 0.96; 95% CI 0.72-1.28). Stratified analysis of clinicopathological features found no significant advantages for improved OS or DSS from adding chemotherapy to adjuvant RT. Thus, in this population database, the use of chemotherapy provided limited survival benefits in advanced major salivary gland cancers after surgical resection.

Upregulated Ubiquitin D is a Favorable Prognostic Indicator for Rectal Cancer Patients Undergoing Preoperative Concurrent Chemoradiotherapy.

Purpose: For locally advanced rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) allows tumor downstaging and makes curative radical proctectomy possible. However, we lack a genetic biomarker to predict cancer prognosis or treatment response. We investigated the association between ubiquitin D (UBD) expression and clinical outcomes in rectal cancer patients receiving CCRT. Patients and Methods: We analyzed the genes associated with the protein modification process (GO:0036211) and identified the UBD gene as the most relevant among the top 7 differentially expressed genes associated with CCRT resistance. We collected tissue specimens from 172 rectal cancer patients who had received CCRT followed by a curative proctectomy. We examine the relationship between UBD expression and patient characteristics, pathological findings, and patient survival, such as metastasis-free survival (MeFS) and disease-specific survival. Results: Upregulated UBD expression was associated with lower pre-CCRT tumor T stage (P = 0.009), lower post-CCRT tumor T stage (P < 0.001), lower post-CCRT nodal stage (P < 0.001), less vascular invasion (P = 0.015), and better tumor regression (P < 0.001). Using univariate analysis, we found that high UBD expression was correlated with better disease-free survival (DFS) (P < 0.0001), local recurrence-free survival (LRFS) (P < 0.0001) and MeFS (P < 0.0001). Moreover, multivariate analysis demonstrated that high UBD expression was associated with superior DFS (P < 0.001), LRFS (P = 0.01), and MeFS (P = 0.004). Conclusion: UBD upregulation was linked to better clinical prognosis, favorable pathological features, and good treatment response in rectal cancer patients undergoing CCRT. These results suggest UBD is a biomarker for rectal cancer.

High SLC28A2 expression endows an inferior survival for rectal cancer patients managed by neoadjuvant CCRT.

For rectal cancer patients with stage T3-4 disease or positive lymph node, neoadjuvant concurrent chemoradiotherapy (CCRT) has become the standard treatment, but the clinical outcomes are still far from satisfactory. Accordingly, a more precise predictive tool such as genetic biomarkers is urgently required to optimize therapy decisions. Colorectal cancer (CRC) development has been considerably correlated with cellular metabolic process involving nucleotides, but the underlying molecular mechanisms remain unclear. In this study, we employed a transcriptome dataset comprising 46 rectal adenocarcinoma patients undergoing preoperative CCRT and focused on nucleobase-containing compound metabolic process (GO: 0055134) for data mining. We identified solute carrier family 28 member 2 (SLC28A2) as the most considerably upregulated gene among rectal cancer patients with CCRT resistance. Afterwards, there were a total of 172 rectal cancer tissue blocks procuring from our biobank, and the immunointensity of SLC28A2 was appraised utilizing immunohistochemical staining. Strong SLC28A2 immunointensity was significantly linked to female patients (p = 0.032), vascular invasion (p = 0.021), and post-CCRT tumor invasion and regional lymph node involvement (p < 0.001 and p = 0.005). Notably, patients with strong SLC28A2 immunointensity had no tumor downstaging (p < 0.001). Univariate analysis revealed that high SLC28A2 immunoexpression was considerably unfavorably linked to all three endpoints: local recurrence-free survival (LRFS), metastasis-free survival (MeFS), and disease-specific survival (DSS) (all p ≤ 0.0333). Moreover, both high SLC28A2 immunoexpression and low tumor regression grade were independently unfavorable prognostic factors for all three endpoints (all p ≤ 0.013) in the multivariate analysis. Utilizing function prediction analysis, SLC28A2 upregulation was more likely to be linked with stem cell homeostasis in rectal cancer. In brief, we demonstrated that high SLC28A2 immunoexpression is substantially linked to an advanced stage, poor response to CCRT, and worse patient survival. Consequently, SLC28A2 expression can be a valuable predictive and prognostic marker for rectal cancer patients and be an encouraging therapeutic target for those with CCRT resistance.

Overexpression of Dehydrogenase/Reductase 9 Predicts Poor Response to Concurrent Chemoradiotherapy and Poor Prognosis in Rectal Cancer Patients.

Objective: To reduce the risk of locoregional recurrence, the addition of neoadjuvant concurrent chemoradiotherapy (CCRT) is recommended before surgical management for rectal cancer patients. However, despite identical tumor histology, individual patient response to neoadjuvant CCRT varies greatly. Accordingly, a comprehensive molecular characterization that is used to predict CCRT efficacy is instantly needed. Methods: Pearson's chi-squared test was utilized to correlate dehydrogenase/reductase 9 (DHRS9) expression with clinicopathological features. Survival curves were created applying the Kaplan-Meier method, and the log-rank test was conducted to compare prognostic utility between high and low DHRS9 expression groups. Multivariate Cox proportional hazards regression analysis was applied to identify independent prognostic biomarkers based on variables with prognostic utility at the univariate level. Results: Utilizing a public transcriptome dataset, we identified that the DHRS9 gene is the most considerably upregulated gene related to epithelial cell differentiation (GO: 0030855) among rectal cancer patients with CCRT resistance. Employing immunohistochemical staining, we also demonstrated that high DHRS9 immunoexpression is considerably associated with an aggressive clinical course and CCRT resistance in our rectal cancer cohort. Among all variables with prognostic utility at the univariate level, only high DHRS9 immunoexpression was independently unfavorably prognostic of all three endpoints (all p ≤ 0.048) in the multivariate analysis. In addition, applying bioinformatic analysis, we also linked DHRS9 with unrevealed functions, such as keratan sulfate and mucin synthesis which may be implicated in CCRT resistance. Conclusion: Altogether, DHRS9 expression may serve as a helpful predictive and prognostic biomarker and assist decision-making for rectal cancer patients who underwent neoadjuvant CCRT.