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Background & Aims: Intrahepatic cholangiocarcinoma (iCCA) has two main histological subtypes: large and small duct‐type iCCA, which are characterized by different clinicopathological features. This study was conducted with the purpose of expanding our understanding of their differences in molecular features and immune microenvironment. Methods: We selected 132 patients who underwent radical surgery at our department between 2015 and 2021 for clinical and survival analyses. Whole‐exome sequencing was performed to analyse mutational landscapes. Bulk RNA sequencing and single‐cell RNA sequencing data were used for pathway enrichment and immune infiltration analyses based on differentially expressed genes. The function of PPP1R1B was analysed both in vitro and in vivo and the gene mechanism was further investigated. Results: We found that large duct‐type iCCA had worse overall survival and recurrence‐free survival rates than small duct‐type iCCA. Mutations in ARID1A, DOT1L and ELF3 usually occur in large duct‐type iCCA, whereas mutations in IDH1 and BAP1 occur in small duct‐type iCCA. Among the differentially expressed genes, we found that PPP1R1B was highly expressed in large duct‐type iCCA tumour tissues. Expression of PPP1R1B promoted cell proliferation, migration and invasion and indicated a worse prognosis. A combination of USF2 with the promoter of PPP1R1B can enhance gene expression in iCCA, which may further affect the expression of genes such as AHNAK, C4BPA and activating the PI3K/AKT pathway. Conclusions: Our findings extend our understanding of large and small duct‐type iCCA. In addition, PPP1R1B may serve as a potential marker and therapeutic target for large duct‐type iCCA. [ABSTRACT FROM AUTHOR]

Intrahepatic cholangiocarcinoma (ICC) is highly heterogeneous. Here, the authors perform exome sequencing and bulk RNA sequencing on 73 tumor regions from 14 ICC patients to portray the multi‐faceted intratumor heterogeneity (ITH) landscape of ICC. The authors show that ITH is highly concordant across genomic, transcriptomic, and immune levels. Comparison of these data to 8 published datasets reveals significantly higher degrees of ITH in ICC than hepatocellular carcinoma. Remarkably, the authors find that high‐ITH tumors highly overlap with the IDH (isocitrate dehydrogenase)‐mutant subgroup (IDH‐SG), comprising of IDH‐mutated tumors and IDH‐like tumors, that is, those IDH‐wildtype tumors that exhibit similar molecular profiles to the IDH‐mutated ones. Furthermore, IDH‐SG exhibits less T cell infiltration and lower T cell cytotoxicity, indicating a colder tumor microenvironment (TME). The higher ITH and colder TME of IDH‐SG are successfully validated by single‐cell RNA sequencing on 17 503 cells from 4 patients. Collectively, the study shows that IDH mutant subgroup status, rather than IDH mutation alone, is associated with ITH and the TME of ICC tumors. The results highlight that IDH‐like patients may also benefit from IDH targeted therapies and provide important implications for the diagnosis and treatment of ICC. [ABSTRACT FROM AUTHOR]

Cancer metastasis has been demonstrated as it is the culmination of a cascade of priming steps. Increasing evidence has shown that tumor-derived molecular components (TDMCs) are known as extra cellular vesicle and nonvesicle factors and serve as versatile intercellular communication vehicles which can mediate signaling in the tumor microenvironment while creating the premetastatic niche. Noncoding RNAs (ncRNAs) as one of the TDMCs have been proved in participating in the formation of the premetastatic niche. Understanding the premetastatic niche formation mechanisms through TDMCs, especially ncRNAs may open a new avenue for cancer metastasis therapeutic strategies. In this review, recent findings regarding ncRNAs function were summarized, and then the interaction with the premetastatic niche formation was studied, which highlight the potential of using ncRNAs for cancer diagnosis and therapeutic effect. [ABSTRACT FROM AUTHOR]

Background. Both splenectomy (SP) and partial splenic embolization (PSE) are used to treat massive splenomegaly (MSM) secondary to hepatitis B-related liver cirrhosis (HB-LC). This retrospective case-control study was conducted to compare the effects of SP and PSE on these patients. Methods. From July 2004 to January 2012, patients with MSM secondary to HB-LC who underwent SP or PSE were 1 : 1 : 1 matched with similar nonsurgery patients, respectively. Intraoperative situation, hematological indices, liver function, HBV DNA level, HBeAg seroconversion rate, morbidity, and mortality at 6 months postoperatively were compared. Results. Operative time, estimated blood loss, blood transfusion rate, severe pain, postoperative stay, and portal vein thrombosis (PVT) rate in the PSE group were significantly superior to the SP group, although SP and PSE were similar in liver function improvement, HBV suppression, morbidity, and mortality at 6 months postoperatively, and SP even improved WBC and PLT counts higher than PSE. Conclusion. Both SP and PSE are effective in improving liver function, increasing WBC and PLT counts, and suppressing replication of HBV for MSM secondary to HB-LC. Although postoperative improvement in WBC and PLT counts by SP can be higher than PSE, PSE is simple and minimally invasive and has a lower incidence of PVT. [ABSTRACT FROM AUTHOR]