Role of CCR1/5/7 in hepatocellular carcinoma: a study on prognostic evaluation, molecular subtyping, and association with immune infiltration.

This study aims to assess the prognostic value of the C-C motif chemokine receptor (CCR) gene family in hepatocellular carcinoma (HCC) and its relationship with immune infiltration and molecular subtypes of HCC. The evaluation of the GSE14520 dataset and TCGA database confirmed the prognostic significance of CCR. Building upon the correlation between CCR1, CCR5, and CCR7 and favorable prognosis, we further validated the prognostic importance of CCR1, CCR5, and CCR7 in ICGC database and an independent cohort from Guangxi autonomous region. Then, we constructed a risk prognosis model. Additionally, we observed significant positive correlations between CCR1, CCR5, and CCR7 and the infiltration of B cells, T cells, and macrophages in HCC. Subsequently, we conducted CCK assays, Transwell assays, and colony formation assays to evaluate the molecular biological functions of CCR1, CCR5, and CCR7. These experiments further confirmed that upregulation of CCR1, CCR5, and CCR7 can individually inhibit the proliferation, migration, and stemness of HCC cells. By analyzing the relationship between expression levels and tumor mutation frequency, we discovered that patients with high CCR1 expression were more likely to be classified as non-proliferative HCC. Similar conclusions were observed for CCR5 and CCR7. The association of CCR1, CCR5, and CCR7 with the molecular subtypes of HCC suggests that they may serve as intermediary molecules linking immune status and molecular subtypes in HCC. In summary, CCR1, CCR5, and CCR7 have the potential to serve as prognostic biomarkers for HCC and regulate HCC progression by influencing immune cell infiltration.

Pancreatic cancer mortality trends attributable to high fasting blood sugar over the period 1990-2019 and projections up to 2040.

Background: Pancreatic cancer (PC) is a prevalent malignancy within the digestive system, with diabetes recognized as one of its well-established risk factors. Methods: Data on PC mortality attributed to high fasting blood sugar were retrieved from the Global Burden of Disease (GBD) study 2019 online database. To assess the temporal trends of PC burden attributable to high fasting plasma glucose (HFPG), estimated annual percentage changes (EAPCs) for age-standardized death rates (ASDRs) between 1990 and 2019 were determined using a generalized linear model. Furthermore, a Bayesian age-period-cohort (BAPC) model using the integrated nested Laplacian approximation algorithm was employed to project the disease burden over the next 20 years. Results: Globally, the crude death number of PC attributable to HFPG almost tripled (from 13,065.7 in 1990 to 48,358.5 in 2019) from 1990 to 2019, and the ASDR increased from 0.36/100,000 to 0.61/100,000 with an EAPC of 2.04 (95% CI 1.91-2.16). The population aged ≥70 years accounted for nearly 60% of total deaths in 2019 and experienced a more significant increase, with the death number increasing approximately fourfold and the ASDR increasing annually by 2.65%. In regions with different sociodemographic indexes (SDIs), the highest disease burden was observed in the high-SDI region, whereas more pronounced increasing trends in ASDR were observed in the low to middle-SDI, low-SDI, and middle-SDI regions. Additionally, a significantly negative association was found between EAPCs and ASDRs of PC attributable to HFPG from 1990 to 2019. Moreover, the BAPC model predicts that ASDR and age-standardized disability-adjusted life-years (DALYs) rate for PC attributed to HFPG was projected to increase obviously for men and women from 2019 to 2040. Conclusions: The burden of PC attributed to HFPG has increased globally over the past three decades, with the elderly population and high-SDI regions carrying a relatively greater disease burden, but more adverse trends observed in low-SDI areas. Furthermore, the burden is projected to continue increasing over the next 20 years. Hence, more tailored prevention methodologies should be established to mitigate this increasing trend.

Sarcosine dehydrogenase as an immune infiltration-associated biomarker for the prognosis of hepatocellular carcinoma.

This study was aimed to investigate the prognostic value and clinical significance of sarcosine dehydrogenase (SARDH) in hepatocellular carcinoma (HCC) and to explore the underlying mechanisms. The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), HPA and CPTAC databases were adopted to analyze the expression of SARDH mRNA and protein between normal liver tissue and HCC, and examine their relationship with clinicopathological features. Kaplan-Meier analysis, Cox regression, as well as nomogram were adopted to explore the prognostic value of SARDH in HCC. Gene Ontology (GO), Kyoto Gene and Genome Encyclopedia (KEGG) together with Gene Set Enrichment Analysis (GSEA) were adopted to analyze the molecular mechanisms and biological functions of SARDH in HCC; while MethSurv, STRING, GeneMANIA, TIMER database data and single-sample gene set enrichment analysis (ssGSEA) algorithm were used for other bioinformatic analysis. Furthermore, immunohistochemistry was used to verify the expression of SARDH. Compared to normal liver tissue, SARDH expression was markedly lower in HCC. A lower SARDH expression was linked with Pathologic T stage (T3&T4), pathologic stage (Stage III&IV), and histologic grade (G3&4), which further indicates worse prognosis. Besides, results of bioinformatic analysis proved that SARDH expression was correlated with immune infiltration. In addition, SARDH hypermethylation was related to a poorer prognosis. SARDH expression was related to several key genes in the Ferroptosis pathway.

Case report: hepatic arterial infusion chemotherapy combined with sintilimab and lenvatinib for conversion therapy of colorectal cancer liver metastases.

Background: Liver metastasis is one of the most common causes of death in patients with colorectal cancer. Therefore, improving the treatment effect of liver metastatic carcinoma of colorectal cancer is also one of the effective ways to improve the survival time of patients with colorectal cancer. The main treatment method for liver metastasis of colorectal cancer is preoperative neoadjuvant chemotherapy through intravenous administration. However, no one has reported a conversion therapy approach for the treatment of colorectal cancer liver metastases patients through arterial infusion chemotherapy combined with targeted agents and PD-1 monoclonal antibody. This case reports a conversion therapy method of liver metastases of colorectal cancer by hepatic arterial infusion chemotherapy (HAIC), sintilimab injection combined with lenvatinib to achieve radical resection of liver metastatic carcinoma after treatment. Case presentation: The patient was a 69-year-old man who had previously undergone laparoscopic left hemicolectomy for descending colorectal cancer and multiple interventional and surgical treatments for hepatocellular carcinoma. During this treatment, the patient underwent radiological and serological tests, and primary liver cancer was considered at the initial diagnosis stage. Therefore, this liver malignant tumor lesion was treated according to the primary liver cancer treatment protocol before surgical resection. Therefore, the patient received HAIC combined with sintilimab injection and lenvatinib. After three treatment cycles, radiological examination showed no obvious tumor activity, alpha-fetoprotein (AFP) decreased to normal, protein induced by vitamin K absence or antagonist II (PIVKA II) decreased significantly, and the curative effect was evaluated as complete remission. Subsequently, we performed surgical resection of this liver lesion. The pathological response of left lobe tumor was partial remission (PR). Most of the tumors were necrotic and the necrosis rate was greater than 95%. A small amount of live tumor tissue remains (<5%). The pathological classification of this tumor was confirmed as moderately differentiated adenocarcinoma by immunohistochemical staining of multiple tumor indicators in the pathology department. No significant adverse drug events were observed in this patient during treatment. Conclusion: Hepatic arterial infusion chemotherapy combined with sintilimab injection and lenvatinib conversion therapy provides the opportunity for radical surgical resection of colorectal cancer liver metastases.