Pancreatic adenosquamous carcinoma (PASC) — a rare pathological pancreatic cancer (PC) type — has a poor prognosis due to high malignancy. To examine the heterogeneity of PASC, we performed single-cell RNA sequencing (scRNA-seq) profiling with sample tissues from a healthy donor pancreas, an intraductal papillary mucinous neoplasm, and a patient with PASC. Of 9,887 individual cells, ten cell subpopulations were identified, including myeloid, immune, ductal, fibroblast, acinar, stellate, endothelial, and cancer cells. Cancer cells were divided into five clusters. Notably, cluster 1 exhibited stem-like phenotypes expressing UBE2C, ASPM, and TOP2A. We found that S100A2 is a potential biomarker for cancer cells. LGALS1, NPM1, RACK1, and PERP were upregulated from ductal to cancer cells. Furthermore, the copy number variations in ductal and cancer cells were greater than in the reference cells. The expression of EREG, FCGR2A, CCL4L2, and CTSC increased in myeloid cells from the normal pancreas to PASC. The gene sets expressed by cancer-associated fibroblasts were enriched in the immunosuppressive pathways. We demonstrate that EGFR-associated ligand-receptor pairs are activated in ductal-stromal cell communications. Hence, this study revealed the heterogeneous variations of ductal and stromal cells, defined cancer-associated signaling pathways, and deciphered intercellular interactions following PASC progression.

Background: Preoperative inflammatory status plays an important role in the prognosis of malignancy. We sought to explore the value of preoperative inflammatory biomarkers in predicting long-term outcomes of liver transplantation (LT) in patients with hepatocellular carcinoma (HCC).Method: Patients who underwent LT for HCC in our hospital between January 2010 and June 2020 were included in this study. Demographic, clinical, laboratory, and outcome data were obtained. The area under the curve (AUC) of the receiver operating characteristic curve was used to evaluate the predictive value of inflammatory biomarkers. The effectiveness of inflammatory biomarkers in predicting outcomes was analyzed by univariate and multivariate Cox proportional hazards analyses.Results: A total of 218 patients were included in the study, with a mean age of 53.9 ± 8.5 years. The AUC of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune inflammation index (SII), and systemic inflammatory response index (SIRI) for overall survival (OS) were 0.741, 0.731, 0.756, 0.746, and 0.749, respectively. Cox proportional hazards model indicated that SIRI > 1.25 was independently associated with low OS [hazard ratio (HR) = 2.258, P = 0.024]. PLR > 82.15 and SIRI > 0.95 were independently associated with low disease-free survival (HR = 1.492, P = 0.015; and HR = 1.732, P = 0.008, respectively). In the survival analysis, the prognosis of patients with high preoperative SIRI and PLR was significantly worse (P < 0.001).Conclusion: SIRI and PLR were useful prognostic markers for predicting patients with HCC after LT.

Pancreatic cancer (PC) is a stubborn malignancy with high lethality and a low 5‑year overall survival (OS) rate. Collagen type VII α1 chain (COL7A1), a major component of the extracellular matrix, serves important roles in numerous physiological processes and various illnesses. COL7A1 protein acts as an anchoring fibril between the external epithelial cells and the underlying stroma, and mutation of COL7A1 could cause recessive dystrophic epidermolysis bullosa. Raw data for PC were acquired from The Cancer Genome Atlas and the Gene Expression Omnibus database, and raw data for the normal pancreas were obtained from the Genotype‑Tissue Expression database. COL7A1 mRNA expression in PC tissues was compared with that in either paired (GSE15471 dataset) or unpaired (all other data) normal pancreas tissues. The association between COL7A1 mRNA expression and clinicopathological factors was assessed using logistic regression analysis. Cox analysis and Kaplan‑Meier analysis were used to evaluate the role of COL7A1 mRNA expression in prognosis and nomograms were constructed. Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, Gene Set Enrichment Analysis (GSEA) and single‑sample GSEA (ssGSEA) were performed to evaluate the relevant functions of COL7A1 and correlation with immune cell infiltration. Furthermore, reverse transcription‑quantitative PCR was used to assess the mRNA expression levels of COL7A1 in PC. The present study demonstrated that COL7A1 mRNA expression was higher in PC tissues compared with in normal pancreas tissues. The Kaplan‑Meier survival analysis indicated that patients with PC with high COL7A1 mRNA expression had shorter overall survival (OS), disease‑specific survival (DSS) and progression‑free interval (PFI) times compared with patients with PC with low COL7A1 mRNA expression. Multivariate analysis demonstrated that COL7A1 mRNA expression was an independent risk factor for OS, DSS and PFI. Nomogram and calibration plots were constructed to predict the prognosis of patients with PC. GSEA demonstrated that high mRNA expression levels of COL7A1 were associated with multiple cancer‑related pathways. ssGSEA analysis indicated that COL7A1 expression was positively associated with natural killer CD56bright cells and T helper (Th)2 cells, and negatively associated with Th17 cells and eosinophils. The results of the present study suggested that COL7A1 could be an independent biomarker and an influential moderator of immune infiltration in PC.

Background: Pancreaticoduodenectomy is the only definitively curative therapy for the long-term survival of distal cholangiocarcinoma patients. Lymph node metastasis is widely accepted as an important prognostic factor for distal cholangiocarcinoma. The latest American Joint Committee on Cancer (AJCC) TNM classification system for distal cholangiocarcinoma has divided the lymph node metastasis patients into N1 and N2 by lymph node metastasis number. However, some studies suggested that the lymph node metastasis ratio may be better than the lymph node metastasis number. Therefore, we develop a program to analyze the correlation between lymph node parameters (lymph node dissection number, lymph node metastasis number, and lymph node metastasis rate) and long-term prognosis. Methods: We retrospectively reviewed 123 distal cholangiocarcinoma patients after pancreatoduodenectomy from January 2011 to December 2019. The patients were grouped according to lymph node metastases and tumor-free and overall survival rates which were investigated with the Kaplan-Meier analysis. The logistic regression models were used for multivariate analysis to determine the risk factors for lymph node metastases. And the X-tile program was used to calculate the cutoff values for the lymph node parameters that discriminated survival. Results: The 1-year, 3-year, and 5-year overall survival rates of patients with distal cholangiocarcinoma after pancreatoduodenectomy were 75.2%, 37.1%, and 31.5%, respectively. And the 1-year, 3-year, and 5-year overall survival rates of patients without and with lymph node metastasis were 83.0%, 50.7%, and 42.5% and 63.5%, 19.0%, and 19.0% (p = 0.000), respectively. Logistic regression showed CA19-9 and portal vein system invasion as independent risk factors for lymph node metastases. The receiver operating characteristic curve showed the optimal cutoff value of CA19-9 to predict the lymph node metastases was 75.5 U/mL. Determined by the X-tile software, the optimal cutoff values of the lymph node dissection number were 24 (p = 0.021), the lymph node metastasis number were 1 and 7 (p = 0.504), and the lymph node metastasis rate were 0.13 (p = 0.002). Conclusion: Lymph node metastasis is an important factor affecting the long-term survival of distal cholangiocarcinoma patients.CA19-9 and portal vein system invasion are independent risk factors for lymph node metastasis. Besides, the lymph node dissection number and lymph node metastasis rate can predict the long-term survival better than lymph node metastasis number.

Previous studies have indicated that sirolimus (SRL) may be effective for HCC patients undergoing liver transplantation (LT). However, the following results are still contradictory and do not have a clear conclusion. Therefore, we conducted an updated meta-analysis by retrieving published data in EMBASE, PubMed, and the Cochrane Library up to October 2017. Both efficiency and safety of SRL were analyzed using pooled odds ratio (ORs) with 95% confidence interval (CIs). A total of 11 studies involving 7,695 HCC patients were included. Compared with control group, SRL prolonged 1-year (OR = 2.44; CI = 1.66–3.59), 3 year (OR = 1.67; CI = 1.08–2.58) and 5-year (OR = 1.68; CI = 1.21–2.33) overall survival, as well as 1-year (OR = 2.13; CI = 1.19–3.81) disease-free survival. Pooled results found that SRL-treated patients had lower recurrence (OR = 0.60; CI = 0.37–0.98), lower recurrence-related mortality (OR = 0.58; CI = 0.42–0.81) and lower overall mortality (OR = 0.62; CI = 0.44–0.89). Moreover, fewer SRL-treated patients suffered from portal vein thrombosis (OR = 0.29; CI, 0.09–0.91) and diabetes (OR = 0.23; CI = 0.12–0.47), while SRL-treated patients were more vulnerable to acne compared with the control group (OR = 4.44; CI = 1.56–12.60). No significant differences in other adverse effects were found between two groups. Taken together, SRL-based immunosuppression is safe and effective in improving survival, as well as reducing recurrence and mortality for HCC patients following LT.