Xiaoyu Xiong’s research while affiliated with Peking University People's Hospital and other places

Colorectal cancer (CRC) continues to be a prevalent malignancy, posing a significant risk to human health. The involvement of alpha/beta hydrolase domain 6 (ABHD6), a serine hydrolase family member, in CRC development was suggested by our analysis of clinical data. However, the role of ABHD6 in CRC remains unclear. This study seeks to elucidate the clinical relevance, biological function, and potential molecular mechanisms of ABHD6 in CRC. We investigated the role of ABHD6 in clinical settings, conducting proliferation, migration, and cell cycle assays. To determine the influence of ABHD6 expression levels on Oxaliplatin sensitivity, we also performed apoptosis assays. RNA sequencing and KEGG analysis were utilized to uncover the potential molecular mechanisms of ABHD6. Furthermore, we validated its expression levels using Western blot and reactive oxygen species (ROS) detection assays. Our results demonstrated that ABHD6 expression in CRC tissues was notably lower compared to adjacent normal tissues. This low expression correlated with a poorer prognosis for CRC patients. Moreover, ABHD6 overexpression impeded CRC cell proliferation and migration while inducing G0/G1 cell cycle arrest. In vivo experiments revealed that downregulation of ABHD6 resulted in an increase in tumor weight and volume. Mechanistically, ABHD6 overexpression inhibited the activation of the AKT signaling pathway and decreased ROS levels in CRC cells, suggesting the role of ABHD6 in CRC progression via the AKT signaling pathway. Our findings demonstrate that ABHD6 functions as a tumor suppressor, primarily by inhibiting the AKT signaling pathway. This role establishes ABHD6 as a promising prognostic biomarker and a potential therapeutic target for CRC patients.

Background We performed this study to identify predictive factors for lymph node metastasis (LNM) and analyze the impact of LNM on the prognosis of patients with T1-2 colorectal cancer (CRC), with the intention of providing guidance for the treatment. Methods The Surveillance Epidemiology and End Result database was used to identify 20,492 patients diagnosed with T1-2 stage CRC between 2010 and 2019, who underwent surgery and lymph node evaluation and had complete prognostic information. Clinicopathological data of patients with T1-2 stage colorectal cancer treated with surgery at Peking University People's Hospital from 2017 to 2021 with complete clinical information were retrieved. We identify and confirm the risk factors for positive lymph node involvement, and the results of follow-up were analyzed. Results Age, preoperative carcinoembryonic antigen (CEA) level, perineural invasion, and primary tumor site were independent risk factors for LNM in T1-2 CRC based on the analysis of the SEER database, while tumor size and histology of mucinous carcinoma were also independent risk factors in T1 CRC. We then make the nomogram model for predicting LNM risk and showed an acceptable consistency and calibration capability. Survival analysis showed that LNM was an independent prognostic indicator of 5-year disease-specific survival (P = 0.013) and disease-free survival (P < 0.001) in patients with T1 and T2 CRC. Conclusion Age, CEA level and primary tumor site should be taken into consideration before making the surgical decision in T1-2 CRC patients. The tumor size and histology of mucinous carcinoma also need to be thought about in T1 CRC. Conventional imaging tests do not appear to provide a precise assessment for this issue.

Staplers have been widely used in the clinical treatment of gastrointestinal reconstruction. However, the current titanium (Ti) staple will remain in the human body permanently, resulting in some adverse effects. In this study, we developed a type of biodegradable staple for colonic anastomosis using 0.3 mm diameter magnesium (Mg) alloy wires. The wire surface was modified by micro-arc oxidation treatment (MAO) and then coated with poly-l-lactic acid (PLLA) to achieve a moderate degradation rate matching the tissue healing process. The results of tensile tests on isolated porcine colon tissue anastomosed by Mg and Ti staples showed that the anastomotic property of Mg staples was almost equal to that of Ti staples. The in vitro degradation tests indicated the dual-layer coating effectively enhanced the corrosion resistance and maintained the tensile force of the coated staple stable after 14-day immersion in the simulated colonic fluid (SCF). Furthermore, 24 beagle dogs were employed to conduct a comparison experiment using Mg-based and clinical Ti staples for 90-day implantation by ent-to-side anastomosis of the colon. The integrated structure of Mg-based staples was observed after 7 days and completely degraded after 90 days. All animals did not have anastomotic leakage and stenosis, and 12 dogs with Mg-based staples fully recovered after 90 days without differences in visceral ion levels and other side effects. The favorable performance makes this Mg-based anastomotic staple an ideal candidate for colon reconstruction.

Objective: To investigate the expression of chromosome 6 open reading frame 15 (C6orf15) in colon cancer and its effects on clinicopathological features and prognosis. Methods: Using the transcriptome and clinical data of colon cancer and normal tissues in The Cancer Genome Atlas (TCGA) database, the expression of C6orf15 mRNA in colon cancer samples and its relationship with clinicopathological characteristics and prognosis were explored. The expression level of C6orf15 protein in 23 colon cancer tissues was detected by immunohistochemistry (IHC). The possible mechanism of C6orf15 involved in the occurrence and development of colon cancer was explored by gene set enrichment analysis (GSEA). Results: Compared with normal tissues, C6orf15 was highly expressed in colon cancer (1.207 ± 0.694 vs 0.276 ± 0.166, t = 8.281, P < 0.01). The expression level of C6orf15 was associated with tumor invasion depth (χ2 = 8.30, P = 0.04), lymph node metastasis (χ2 = 36.97, P < 0.001), distant metastasis (χ2 = 8.69, P = 0.003) and pathological stage (χ2 = 34.17, P < 0.001). High expression of C6orf15 was associated with poor prognosis (χ2 = 6.43, P < 0.05). The results of GSEA showed that C6orf15 promotes the occurrence and development of colon cancer by promoting the ECM receptor interaction pathway, Hedgehog signaling pathway and Wnt signaling pathway. Immunohistochemical results showed that the expression of C6orf15 protein in colon cancer tissues was correlated with the depth of invasion (P = 0.023) and lymph node metastasis (P = 0.048). Conclusion: C6orf15 is highly expressed in colon cancer tissue and is related to adverse pathological features and poor prognosis of colon cancer. It is involved in multiple oncogenic signaling pathways and may serve as a prognostic marker of colon cancer.

Faced with the high heterogeneity and poor prognosis of colorectal cancer (CRC), this study sought to find new predictive prognostic strategies to improve the situation. Cuproptosis is a novel cell death mechanism that relies on copper regulation. However, the role of cuproptosis-related gene (CRG) in CRC remains to be elucidated. In this study, we comprehensively assessed the CRG landscape in CRC based on The Cancer Genome Atlas (TCGA). We identified differential expression and genetic alterations of CRG in CRC. CRG is highly correlated with initiation, progression, prognosis, and immune infiltration of CRC. We construct a risk score signature containing 3 CRGs based on LASSO. We explored the correlation of CRG-Score with clinicopathological features of CRC. Age, stage, and CRG-Score were integrated to construct a nomogram. The nomogram has robust predictive performance. We also understand the correlation of CRG-Score with CRC immune landscape. CRG-Score can effectively predict the immune landscape of CRC patients. Low-risk CRC patients have greater immunogenicity and higher immune checkpoint expression. Low-risk CRC patients may be better candidates for immunotherapy. At the same time, we also predicted more sensitive drugs in the high-risk CRC patients. In conclusion, the CRG risk score signature is a strong prognostic marker and may help provide new insights into the treatment of individuals with CRC.

Objective To investigate the expression of chromosome 6 open reading frame 15 (C6orf15) in colon cancer and its effects on clinicopathological features and prognosis. Methods Using the transcriptome and clinical data of colon cancer and normal tissues in The Cancer Genome Atlas (TCGA) database, the expression of C6orf15 mRNA in colon cancer samples and its relationship with clinicopathological characteristics and prognosis were explored. The expression level of C6orf15 protein in 23 colon cancer tissues was detected by immunohistochemistry (IHC). The possible mechanism of C6orf15 involved in the occurrence and development of colon cancer was explored by gene set enrichment analysis (GSEA). Results Compared with normal tissues, C6orf15 was highly expressed in colon cancer (1.207±0.694 vs. 0.276±0.166, t=8.281, P<0.01). The expression level of C6orf15 was associated with tumor invasion depth (χ2=8.30, P=0.04), lymph node metastasis (χ2=36.97, P<0.001), distant metastasis (χ2=8.69, P=0.003), pathological stage (χ2=34.17, P<0.001). High expression of C6orf15 was associated with poor prognosis (χ2=6.43, P<0.05). The results of GSEA showed that C6orf15 promotes the occurrence and development of colon cancer by promoting the ECM receptor interaction pathway, Hedgehog signaling pathway and Wnt signaling pathway. Immunohistochemical results showed that the expression of C6orf15 protein in colon cancer tissues was correlated with the depth of invasion (P=0.023) and lymph node metastasis (P=0.048). Conclusion C6orf15 is highly expressed in colon cancer tissue and is related to adverse pathological features and poor prognosis of colon cancer. It is involved in multiple oncogenic signaling pathways and may serve as a prognostic marker of colon cancer.

Aim We aimed to compare the safety and oncological outcomes of transanal endoscopic microsurgery (TEM) and radical surgery (RS) for patients with T1 or T2 rectal cancer. Method We searched Pubmed, Embase, Cochrane Library databases for relevant studies comparing TEM with RS in rectal cancer published until April 2020. We focused on safety and oncological outcomes. Results This meta-analysis included 3526 patients from 12 studies. Compared with RS, TEM had a shorter operative time (weighted mean difference [WMD] −110.02, 95% confidence interval [CI]: 143.98, −76.06), less intraoperative blood loss (WMD -493.63, 95% CI: 732.66, −214.59), lower perioperative morality (risk ratio [RR] 0.25, 95% CI: 0.06, 0.99), and fewer postoperative surgical complications (RR 0.23, 95% CI: 0.11,0.45). TEM was associated with more patients with a positive margin or a doubtfully complete margin than RS (RR 7.36, 95% CI: 3.66, 14.78). TEM was associated with higher local recurrence (RR 2.63, 95% CI: 1.60, 4.31) and overall recurrence (RR 1.60, 95% CI: 1.09, 2.36). TEM had a negative effect on 5-year overall survival (hazard ratio [HR] 1.51, 95% CI: 1.16, 1.96), especially in the T2 without neoadjuvant therapy (NAT) subgroup (HR 2.02, 95% CI: 1.32, 3.09), but in the subgroups of T1 or T2 with NAT before TEM, TEM did not yield a significantly lower overall survival than RS. Conclusion TEM seems appropriate for T1 rectal cancer with favourable histopathology. For patients with T2 rectal cancer, NAT before TEM may contribute to achieving oncological outcomes equivalent to that achieved with RS.