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BackgroundAlthough neoadjuvant therapy has brought numerous benefits to patients, not all patients can benefit from it. Chemokines play a crucial role in the tumor microenvironment and are closely associated with the prognosis and treatment of colorectal cancer. Therefore, constructing a prognostic model based on chemokines will help risk stratification and providing a reference for the personalized treatment.MethodsEmploying LASSO-Cox predictive modeling, a chemokine-based prognostic model was formulated, harnessing the data from TCGA and GEO databases. Then, our exploration focused on the correlation between the chemokine signature and elements such as the immune landscape, somatic mutations, copy number variations, and drug sensitivity. CXCL10+M1 macrophages identified via scRNA-seq. Monocle2 showed cell pseudotime trajectories, CellChat characterized intercellular communication. CytoTRACE analyzed neoadjuvant therapy stemness, SCENIC detected cell type-specific regulation. Lastly, validation was performed through multiplex immunofluorescence experiments.ResultsA model based on 15 chemokines was constructed and validated. High-risk scores correlated with poorer prognosis and advanced TNM and clinical stages. Individuals presenting elevated risk scores demonstrated an increased propensity towards the development of chemotherapy resistance. Subsequent scRNA-seq data analysis indicated that patients with higher presence of CXCL10+ M1 macrophages in tumor tissues are more likely to benefit from neoadjuvant therapy.ConclusionWe developed a chemokine-based prognostic model by integrating both single-cell and bulk RNA-seq data. Furthermore, we revealed epithelial cell heterogeneity in neoadjuvant outcomes and identified CXCL10+ M1 macrophages as potential therapy response predictors. These findings could significantly contribute to risk stratification and serve as a key guide for the advancement of personalized therapeutic approaches.

Abstract Empowered by recent advances of sequencing techniques, transcriptome-wide studies have characterized over 150 different types of post-transcriptional chemical modifications of RNA, ranging from methylations of single base to complex installing reactions catalyzed by coordinated actions of multiple modification enzymes. These modifications have been shown to regulate the function and fate of RNAs and further affecting various cellular events. However, the current understanding of their biological functions in human diseases, especially in cancers, is still limited. Once regarded as “junk” or “noise” of the transcriptome, noncoding RNA (ncRNA) has been proved to be involved in a plethora of cellular signaling pathways especially those regulating cancer initiation and progression. Accumulating evidence has demonstrated that ncRNAs manipulate multiple phenotypes of cancer cells including proliferation, metastasis and chemoresistance and may become promising biomarkers and targets for diagnosis and treatment of cancer. Importantly, recent studies have mapped plenty of modified residues in ncRNA transcripts, indicating the existence of epigenetic modulation of ncRNAs and the potential effects of RNA modulation on cancer progression. In this review, we briefly introduced the characteristics of several main epigenetic marks on ncRNAs and summarized their consecutive effects on cancer cells. We found that ncRNAs could act both as regulators and targets of epigenetic enzymes, which indicated a cross-regulating network in cancer cells and unveil a novel dimension of cancer biology. Moreover, by epitomizing the knowledge of RNA epigenetics, our work may pave the way for the design of patient-tailored therapeutics of cancers.

Metastasis remains to be one of the most prevalent causes leading to poor long-term survival of colorectal cancer (CRC) patients. The clinical significances of tumor metastatic suppressor, N-myc downregulated gene 1 (NDRG1), have been inconsistently reported in a variety of cancerous diseases. In this study with 240 CRC clinical specimens, we showed that NDRG1 expression was significantly decreased in most of CRC tissues compared to the paired non-tumor counterparts. Statistical analysis revealed a significant inverse correlation of NDRG1 expression with tumor stage, differentiation status and metastasis. Compared with NDRG1-negative group, NDRG1-positve group had better disease-free/overall survival (p = 0.000) over 5 years' follow-up. Furthermore, NDRG1 was considered to be an independent prognostic factor for overall survival (p = 0.001) and recurrence (p = 0.003). Our study concludes that NDRG1 is a novel favorable predictor for the prognosis in CRC patients.

Background: Although neoadjuvant therapy has brought numerous benefits to patients, not all patients can benefit from it. Chemokines play a crucial role in the tumor microenvironment and are closely associated with the prognosis and treatment of colorectal cancer. Therefore, constructing a prognostic model based on chemokines will help risk stratification and providing a reference for the personalized treatment. Methods: Employing LASSO-Cox predictive modeling, a chemokine-based prognostic model was formulated, harnessing the data from TCGA and GEO databases. Then, our exploration focused on the correlation between the chemokine signature and elements such as the immune landscape, somatic mutations, copy number variations, and drug sensitivity. CXCL10+M1 macrophages identified via scRNA-seq. Monocle2 showed cell pseudotime trajectories, CellChat characterized intercellular communication. CytoTRACE analyzed neoadjuvant therapy stemness, SCENIC detected cell type-specific regulation. Lastly, validation was performed through multiplex immunofluorescence experiments. Results: A model based on 15 chemokines was constructed and validated. High-risk scores correlated with poorer prognosis and advanced TNM and clinical stages. Individuals presenting elevated risk scores demonstrated an increased propensity towards the development of chemotherapy resistance. Subsequent scRNA-seq data analysis indicated that patients with higher presence of CXCL10+ M1 macrophages in tumor tissues are more likely to benefit from neoadjuvant therapy. Conclusion: We developed a chemokine-based prognostic model by integrating both single-cell and bulk RNA-seq data. Furthermore, we revealed epithelial cell heterogeneity in neoadjuvant outcomes and identified CXCL10+ M1 macrophages as potential therapy response predictors. These findings could significantly contribute to risk stratification and serve as a key guide for the advancement of personalized therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: E2A gene, which encodes two basic helix-loop-helix (bHLH) transcription factors E12 and E47, has been identified as regulator of B lymphoid hematopoiesis and suppressor of lymphoma. E47 protein was found to decrease E-cadherin expression and induce epithelial-mesenchymal transition (EMT). However, the role of E2A in colorectal cancer (CRC) metastasis is still elusive.Methods: qRT-PCR and semi-qRT-PCR were performed to determine mRNA level of E2A in CRC specimens and colorectal cancer cells. RNAi was employed to downregulate E2A expression and subsequent protein level change was evaluated by immunoblot. Cell invasion and migration capacity were detected by transwell assay using cell culture inserts with or without basement membrane matrix, respectively.Results: E2A expression was decreased in metastatic CRC tissues. Invasion and migration assays showed downregulation of E2A increased metastatic capacity of CRC cells while forced expression of E12 or E47 could offset this effect. Both E12 and E47 suppressed EMT induced by E2A downregulation. Moreover, Yes-Associated Protein (YAP) was a downstream target of E2A and suppression of YAP inhibited the pro-migration/invasion of E2A deficiency.Conclusion: Our results suggest that E2A suppresses CRC cell metastasis, at least partially if not all, by inhibiting YAP expression. [ABSTRACT FROM AUTHOR]

Objective: The aims of this study were to investigate the effects of carbon-dioxide (CO2) insufflation on hemodynamic and respiratory function during laparoscopic inguinal hernioplasty and to evaluate the safety of transabdominal preperitoneal hernia repair (TAPP) and extraperitoneal hernia repair (TEP). Materials and Methods: Forty patients with inguinal hernia were admitted for laparoscopic inguinal hernia repair in our study. The patients were randomly assigned to undergo TAPP (TAPP group, n = 20) or TEP (TEP group, n = 20). Hemodynamic and respiratory parameters, including heart rate, blood pressure, end-tidal CO2 (EtCO2), and blood-gas parameters, were observed and compared between the two groups. Results: There was no significant difference between the two groups in terms of sex, age, American Society of Anesthesiology degree, body-mass index, type of hernia, operation time, hospital stay, and postoperative pain score. In both groups, 5 minutes into the operation, blood pressure, EtCO2, PaCO2, and HCO3− increased significantly, whereas heart rate and pH decreased significantly ( P < 0.05). The above tendency became significant with the operation prolonged. All parameters recovered to normal levels at the end of surgery. No significant difference was found between the TAPP and TEP groups. Conclusions: Both TAPP and TEP procedures can result in CO2 accumulation, acidosis, increased blood pressure, and decreased heart rate. But, these effects were transient and could be well controlled by appropriate treatments during the operation. The laparoscopic TAPP and TEP techniques are safe for patients by proper perioperative management. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the inflammatory response and acid-base equilibrium index, as well as other clinical facts of the endoscopic thyroidectomy via the anterior chest wall approach. Methods: Thirty-nine patients who received thyroidectomy in our surgical center during September 2007 and January 2008 were included in this study. Twenty of the patients underwent an endoscopic surgery, and the remaining 19 received conventional surgery. These patients' data were compared within and between treatment groups with respect to clinical facts and inflammatory evaluations. Arterial blood gas data and electrolyte data were analyzed within the endoscopic group. Results: Endoscopic thyroidectomy group showed shorter operative time, compared to that of the conventional thyroidectomy group, although the difference didn't reach statistical significance. No significant difference regarding postoperative hospital stay was observed between two groups. Postoperative day 1 shows much higher values of interleukin-6 and tumor necrosis factor than that measured preoperative or postoperative day 3 in both groups. C-reactive protein appeared to be significantly increased postoperatively in both groups, although no difference between the two groups was found. Although blood cortisol significantly increased in both groups postoperatively, the data of endoscopic group postoperative day 1 was lower than the same day of the conventional group. Arterial blood gas analysis showed that both PCO2 and TCO2 were statistically different between preoperation and 30 minutes after insufflation. No insufflation complication was observed. Conclusion: Compared with conventional thyroid surgery, endoscopic thyroidectomy via the anterior chest wall approach presented with no significant difference in respect of both clinical facts and laboratory outcomes. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to summary the experiences and lessons from periduodenal perforations related to endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (EST). Methods: A retrospective review from 2004 to 2007 identified 9 patients (0.37%) of periduodenal perforation related to ERCP/EST. Charts were reviewed for the following parameters: clinical presentation of patients, ERCP findings, diagnostic methods, treatment (surgical or conservative procedures), complications, and outcome. Results: Nine patients who had periampullary perforations received ERCP/EST for common bile duct stones. Cannulation was considered difficult in 7 of 9 patients, and the precut technique was used. The diagnosis was made due to subcutaneous emphysema or peritonitis, and 3 patients received emergent operations (e.g., external biliary or retroperitoneal drainage), and 1 patient had a reoperation for a retroperitoneal sealed abscess. Their median length of hospital stay was 50 days. The other 6 were treated conservatively with nasal-duodenal and nasal-biliary drainage. Their median length of hospital stay was 13 days. There was no mortality. Conclusions: The precut technical may be a risk factor of duodenal perforation. Early diagnosis of duodenal perforation is essential for an optimum outcome, and subcutaneous emphysema may be a sensitive sign. Although the management of perforation after ERCP/EST is still controversial, a selective management is proposed, based on the features of classification type. Nevertheless, duodenal and biliary drainage is essential in both surgical and conservative therapy. [ABSTRACT FROM AUTHOR]