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Nasopharyngeal carcinoma (NPC) is a kind of epithelial carcinoma that is common in East and Southeast Asia. Distant metastasis after radiotherapy remains the main cause of treatment failure and preradiotherapy immune system function can influence prognosis. Our study aimed to identify immune-related prognostic factors for NPC after radiotherapy and establish a prognostic model to predict progression-free survival (PFS) and distant metastasis-free survival (DMFS). We enrolled NPC patients and divided them into training and validation cohorts with follow-up. We collected clinical information and investigated immune cells, EBV DNA and cytokines in the peripheral blood of NPC patients before radiotherapy and EBV DNA after radiotherapy. Among these immune cells, we included CD8 CD28 T cells, which are a unique T-cell immunosenescent subset that increases in human peripheral blood with increasing age and declining immune function. Based on the detection results and clinical information, we utilized Cox regression and least absolute shrinkage and selection operator (LASSO) regression to screen the PFS and DMFS prognostic factors and build nomograms to predict the PFS and DMFS of NPC. We also verified the results in the validation set. Three factors associated with PFS were selected: proportion of CD8 CD28 T cells posttreatment EBV and N stage. Three factors associated with DMFS were screened: proportion of CD8 CD28 T cells, posttreatment EBV and N stage. CD8 CD28 T cells are correlated with systemic inflammation and posttreatment immunosuppression. The C-indexes were 0.735 and 0.745 in the training and validation cohorts for predicting PFS. For DMFS, the C-indexes were 0.793 and 0.774 in the training and validation cohorts. The pretreatment proportion of CD8 CD28 T cells is a candidate prognostic biomarker for NPC after radiotherapy. The constructed nomogram models based on CD8 CD28 T cells have good predictive value.

Rectal cancer accounts for approximately 40% of colorectal cancer cases, and lateral pelvic lymph node (LPLN) metastasis in rectal cancer significantly increases the local recurrence rate. Despite its clinical significance, studies on the molecular biology of LPLN metastasis are relatively scarce. In this study, we aimed to elucidate the underlying mechanisms by identifying hub regulatory genes in LPLN tissues and analyzing differentially expressed genes shared between tumor and pericarcinomatous tissues within our clinical cohort. To investigate the biological functions of these hub regulatory genes, we performed GSEA, GO, and KEGG pathway analyses on mRNA-Seq data. Among the identified hub genes, KLF12 emerged as a pivotal regulatory gene in rectal cancer. We further explored its clinical relevance and biological function. Our findings, validated using public databases, clinical cohort data, and immunohistochemistry (IHC), identified KLF12 as a specific marker for LPLN. Additionally, KLF12 expression exhibited a strong correlation with disease-free survival (DFS). According to clinical data, significant differences in KLF12 expression exist between groups based on factors such as age, gender, tumor location, pathological N stage, and postoperative tumor residue. Both treatment outcomes (DFS) and receiver operating characteristic curves (AUCs) were significantly associated with KLF12 expression. Furthermore, KLF12 demonstrated a strong association with immune cell infiltration, immune checkpoint expression, and immunophenoscore (IPS), indicating its potential regulatory role in immunotherapy. Functional molecular experiments revealed that KLF12 overexpression inhibited the proliferation, migration, and invasion of SW620 cells. In conclusion, leveraging mRNA-Seq data, TCGA database analysis, immune infiltration data, and biological function assessments, we confirmed that KLF12 could serve as an effective predictive marker and potential therapeutic target for LPLN metastasis. These findings suggest that KLF12 may be instrumental in assessing predictive risk and identifying novel therapeutic targets for patients with rectal cancer.

BackgroundColorectal cancer (CRC) is the most common digestive cancer in the world. Microsatellite stability (MSS) and microsatellite instability (MSI-high) are important molecular subtypes of CRC closely related to tumor occurrence and progression and immunotherapy efficacy. The presence of CD8+ CXCR5+ follicular cytotoxic T (TFC) cells is strongly associated with autoimmune disease and CD8+ effector function. However, the roles of TFC cells in MSI-high CRC and MSS CRC are unclear. Here, we aimed to explore the characteristics of TFC cells in CRC and compare their biological functions between MSI-high and MSS CRC.MethodsWe explored the expression of TFC cell in tumor tissues and peripheral blood in our clinical cohort and public datasets. By combining single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing, we explored the potential function of TFC cells and developed a prediction model for CRC. We also compared the biological functions of these cells between MSS and MSI-high CRC and used flow cytometry and coculture experiments to explore their potential regulatory functions.ResultsTFC cell markers are downregulated in tumor tissues and patient peripheral blood vs. controls. The prediction model for CRC performed well in the training and validation cohorts (KM plot p < 0.001). MSS CRC patients exhibit enrichment of genes related to the cell cycle (MKI67) and T cell activation (CD38 and HLA-DR) and decreased enrichment of immune checkpoint markers (PD1, TIM3, and LAG3). The expression of TFC cell-related genes is positively correlated with that of CD8+IFN-γ+-related genes and closely related to that of TLS-related genes in MSS CRC. The proportion of TFC cells is positively correlated with that of CD19+CD38+ B cells in MSS CRC.ConclusionsThe prognostic prediction model has good predictive value. In MSS CRC, TFC cells function mostly in T cell activation and the cell cycle and have low expression of immune checkpoint molecules, which may influence the effectiveness of ICB therapy. TFC cells may regulate antitumor function by regulating CD19+ CD38+ B cells and TLSs.

Background Nasopharyngeal carcinoma (NPC) is a kind of epithelial carcinoma that is common in East and Southeast Asia. Distant metastasis after radiotherapy remains the main cause of treatment failure and preradiotherapy immune system function can influence prognosis. Our study aimed to identify immune-related prognostic factors for NPC after radiotherapy and establish a prognostic model to predict progression-free survival (PFS) and distant metastasis-free survival (DMFS). Methods We enrolled NPC patients and divided them into training and validation cohorts with follow-up. We collected clinical information and investigated immune cells, EBV DNA and cytokines in the peripheral blood of NPC patients before radiotherapy and EBV DNA after radiotherapy. Among these immune cells, we included CD8 + CD28 − T cells, which are a unique T-cell immunosenescent subset that increases in human peripheral blood with increasing age and declining immune function. Based on the detection results and clinical information, we utilized Cox regression and least absolute shrinkage and selection operator (LASSO) regression to screen the PFS and DMFS prognostic factors and build nomograms to predict the PFS and DMFS of NPC. We also verified the results in the validation set. Results Three factors associated with PFS were selected: proportion of CD8 + CD28 − T cells posttreatment EBV and N stage. Three factors associated with DMFS were screened: proportion of CD8 + CD28 − T cells, posttreatment EBV and N stage. CD8 + CD28 − T cells are correlated with systemic inflammation and posttreatment immunosuppression. The C-indexes were 0.735 and 0.745 in the training and validation cohorts for predicting PFS. For DMFS, the C-indexes were 0.793 and 0.774 in the training and validation cohorts. Conclusions The pretreatment proportion of CD8 + CD28 − T cells is a candidate prognostic biomarker for NPC after radiotherapy. The constructed nomogram models based on CD8 + CD28 − T cells have good predictive value.

Background/Objectives: The metastatic patterns of apical lymph node (ALN) in rectal and sigmoid colon cancer are currently unclear, and there is no consensus on the indications for dissection of ALN. This study aimed to analyze the impact of ALN metastasis on prognosis, determine the metastatic patterns of ALN and provide evidence for indications of ALN dissection in rectal and sigmoid colon cancer. Methods: In this multicenter, retrospective cohort study, patients from five centers with stage I-III rectal or sigmoid colon cancer who underwent laparoscopic radical surgery with ALN dissection without neoadjuvant treatment from January 2015 to December 2019 were enrolled. Results: Among 2809 patients, the positive rate of ALN was 1.9%. The 5-year overall survival and cancer-specific survival rate for patients with metastatic ALN were 37.5% and 41.0%, respectively. ALN metastasis was the independent risk factor for poor prognosis. Tumor size ≥5 cm (OR = 2.32, 95% CI: 1.30–4.13, p = 0.004), signet ring cell cancer/mucinous adenocarcinoma (vs. poor differentiated adenocarcinoma, OR = 0.19, 95% CI: 0.08–0.45, p < 0.001; vs. moderate to well differentiated adenocarcinoma, OR = 0.22, 95% CI: 0.11–0.42, p < 0.001), T4 stage (OR = 1.93, 95% CI: 1.05–3.55, p = 0.034), N2 stage (OR = 8.86, 95% CI: 4.45–17.65, p < 0.001) and radiologic evidence of extramural venous invasion (OR = 1.88, 95% CI: 1.03–3.42, p = 0.040) were independent risk factors for ALN metastasis. The nomogram model developed by these factors achieved a good predictive performance. Conclusions: This research offered insights into the incidence, risk factors, and prognostic significance of apical lymph node metastasis in cases of rectal and sigmoid colon cancer. Additionally, the study furnished empirical support for the criteria guiding ALN dissection. Furthermore, a pragmatic risk assessment model was developed to predict ALN metastasis.

Purpose Few studies have focused on anastomotic recurrence (AR) in colon cancer. This study aimed to clarify the association of resection margin distance with AR and compare the prognosis with nonanastomotic local recurrence (NAR). Methods This retrospective cohort study included the clinical data of patients who underwent radical colon cancer surgery between January 1, 2009, and December 31, 2019. Results A total of 1958 colon cancer patients were included in the study. 34 of whom (1.7%) had AR and 105 of whom (5.4%) had NAR. Multivariate analysis revealed that the lower distal resection margin distance, advanced N stage, and number of lymph nodes dissected were risk factors for AR. In the proximal resection margin, the risk of AR was lowest at a distance of 6 cm or greater, with a 3-year rate of 1.3%. In the distal resection margin, the 3-year AR risk increased rapidly if the distance was less than 3 cm. The prognosis of patients in the AR group was similar to that of patients in the NAR group, regardless of synchronous distant metastases. Furthermore, the radical surgery rate for AR was significantly higher than that for NAR, but the prognosis of AR was comparable to that of NAR. Conclusions The distal resection margin distance, advanced N stage, and less number of lymph nodes dissected are associated with AR of colon cancer. The prognosis of patients with AR was similar to that of patients with NAR. Trial registration Clinical Trial Numbers NCT04074538 ( clinicaltrials.gov ), August 26, 2019, registered, retrospectively registered.

One of the most important changes in the transformation of normal cells into tumor cells is metabolism. In order to satisfy the more active proliferation, migration and metastasis of cancer cells, abnormal changes occur in various pathways and molecules involved in metabolism, which eventually lead to metabolic reprogramming of tumor cells. This process involves the uptake of nutrients and changes in major metabolic forms. As an important part of post-transcriptional epigenetics, RNA methylation modifications can regulate RNA processing and metabolism, while dynamically and reversibly influencing the expression of specific molecules, thereby ultimately affecting diverse biological processes and cellular phenotypes. In this review, various types of RNA methylation modifications involved in cancer are summarized. Subsequently, we systematically elucidate the mechanism of RNA modification for metabolic reprogramming in cancer, including glucose, lipid, amino acid and mitochondrial metabolism. Most importantly, we discuss in depth the clinical significance of RNA modification in metabolic targeted therapy and immunotherapy from mechanism to therapeutic application.

Adjuvant chemotherapy is the standard management approach for patients with stage II/III colon cancer; However, the effectiveness in older patients is still unclear. This study aimed to explore the efficacy of adjuvant chemotherapy and whether oxaliplatin-based chemotherapy has better oncological outcomes than capecitabine monotherapy in older patients with stage III and high-risk stage II colon cancer. We analyzed and compared oxaliplatin-based adjuvant chemotherapy with capecitabine monotherapy and no chemotherapy in 468 patients aged ≥70 years with stage III and high-risk stage II colon cancer, and a propensity score-matched analysis was conducted. The endpoints were overall survival (OS), cancer-specific survival (CSS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS). Firstly, this study compared adjuvant chemotherapy with no adjuvant chemotherapy, statistically significant differences were observed in OS and CSS at the treatment arm and age groups (5-year OS rate: 84.6% vs. 65.9%, P <0.001; 5-year CSS rate: 87.9% vs. 77.5%, P = 0.012), but no difference was observed in LRFS or DMFS. The subgroup analysis suggested that no statistically significant benefits were observed between oxaliplatin-based adjuvant chemotherapy and capecitabine monotherapy, and no significant differences in chemotherapy duration were detected with ≥6 months of therapy compared with 3-6 months (exluding 6 months) of therapy. Older patients with stage III or high-risk stage II colon cancer can benefit from adjuvant chemotherapy, and capecitabine monotherapy has non-inferior oncological outcomes compared with oxaliplatin-based regimens. ClinicalTrials.gov, NCT04074538.

To address the challenge posed by the growing global energy demand, perovskite solar cells (PSCs) present a sustainable and clean solution with the advantage of low cost, high power conversion efficiency (PCE) and easy processing features [...]