[Expression of miRNA let-7a and HMGA2 and Diagnostic Value of Serum miRNA let-7a Level in Pancreatic Cancer].

OBJECTIVE: To investigate the diagnostic value of miRNA let-7a, high mobility group A2 (HMGA2) expression and serum miRNA let-7a level in pancreatic cancer. METHODS: From January 2014 to January 2019, 60 patients with pancreatic cancer were collected for fresh pancreatic ductal adenocarcinoma tissue and normal pancreatic tissue adjacent to the cancer after the operation. Serum samples before and after operation were also collected, while 60 healthy people were enrolled as the control group. The expression of miRNA let-7a (qRT-PCR) and HMGA2 (qRT-PCR and Western blot) in cancer and adjacent normal tissues were measured. The serum level of miRNA let-7a was detected by qRT-PCR. The relationship between miRNA let-7a and HMGA2 expression and the clinicopathological features of pancreatic cancer was analyzed. The diagnostic value of serum miRNA let-7a pre-operation in patients with pancreatic cancer was also analyzed with ROC curve. RESULTS: Compared with normal tissues adjacent to the cancer, the expression level of miRNA let-7a in pancreatic cancer tissues decreased ( t=20.291, P<0.01), and the expression of HMGA2 mRNA increased ( t=46.681, P<0.01). The expression of HMGA2 protein in cancer tissues was higher than that in normal tissues adjacent to the cancer ( t=22.973, P<0.01). The serum level of miRNA let-7a in pancreatic cancer patients was significantly lower than that in healthy controls ( t=24.854, P<0.01). The relative level of serum miRNA let-7a at 1 week after surgery was significantly lower than that before surgery in pancreatic cancer patients ( t=6.885, P<0.01). There was a positive correlation between cancer tissue and serum miRNA let-7a expression 1 week after surgery ( r=0.411, P=0.000). The relative expression levels of miRNA let-7a and HMGA2 in pancreatic cancer tissues were significantly different in different TNM stages and lymph node metastasis ( P<0.05). The area under curve of pre-operation serum miRNA let-7a for the diagnosis of pancreatic cancer was 0.823 ( 95% confidence interval: 0.665-0.917); when the optimal cut-off value of miRNA let-7a was 0.614, the sensitivity was 82.3%, the specificity was 74.1%. CONCLUSION: The expression of HMGA2 may be involved in the invasion and metastasis of pancreatic cancer. The level of serum miRNA let-7a may provide a reference for the diagnosis and postoperative monitoring of pancreatic cancer.

Certain Dietary Habits Contribute to the Functional Dyspepsia in South China Rural Area.

BACKGROUND Functional dyspepsia (FD) refers to a group of upper gastrointestinal syndromes, subdivided into two types: postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). The etiology of FD remains unclear; however, unhealthy dietary habit is one potential underlying cause. We aim to explore the association of poor dietary habits with FD and its subtypes. MATERIAL AND METHODS A validated epidemiological questionnaire was designed to investigate dietary habits and gastrointestinal syndromes. Citizens in the Baotun community of Dongguan were invited to complete the study questionnaire. All participants were asked to undergo a physical examination and a blinded physician interview. The study was conducted from June 2015 to June 2016. FD was diagnosed using ROME III criteria. The association between investigated dietary habits and dyspeptic symptoms were explored. RESULTS There were 1,304 adult residents recruited for the study survey; 165 residents had existing organic dyspepsia (OD), 203 residents were diagnosed with FD, and the other 936 participants, who were without dyspeptic symptoms or functional gastrointestinal diseases, were regarded as the control group. Subtype diagnosis indicated 61 participants had EPS, 66 participants had PDS, and 76 participants had coexisting EPS and PDS. Unhealthy dietary habits were more prevalent in the FD group than in the control groups (75.86% versus 37.50%; p<0.001). FD was found to be associated with irregular mealtime, dining out, fatty food, sweet food, and coffee (p<0.05). The impact of each dietary factor varied with FD subtypes. CONCLUSIONS Certain types of dietary habits were positively correlated with the prevalence of FD. FD subtypes showed relatively different associations with dietary factors.

LncRNA BC promotes lung adenocarcinoma progression by modulating IMPAD1 alternative splicing.

BACKGROUND: The therapeutic value of targeted therapies in patients with lung cancer is reduced when tumours acquire secondary resistance after an initial period of successful treatment. However, the molecular events behind the resistance to targeted therapies in lung cancer remain largely unknown. AIMS: To discover the important role and mechanism of lncRNA BC in promoting tumor metastasis and influencing clinical prognosis of LUAD. MATERIALS & METHODS: Microarrays were used to screen a comprehensive set of lncRNAs with differential expression profiles in lung cancer cells. The functional role and mechanism of lncRNA were further investigated by gain- and loss-of-function assays. RNA pull-down, protein assays, and mass spectrometry were used to identify proteins that interacted with lncRNA. TaqMan PCR was used to measure lncRNA in lung adenocarcinoma and adjacent nontumor tissues from 428 patients. The clinical significance of lncRNA identified was statistically confirmed in this cohort of patients. RESULTS: In this study, we show that the long non-coding RNA BC009639 (BC) is involved in acquired resistance to EGFR-targeted therapies. Among the 235 long non-coding RNAs that were differentially expressed in lung cancer cell lines, with different metastatic potentials, BC promoted growth, invasion, metastasis, and resistance to EGFR-tyrosine kinase inhibitors (EGFR-TKIs), both in vitro and in vivo. BC was highly expressed in 428 patients with lung adenocarcinoma (LUAD) and high BC expression correlated with reduced efficacy of EGFR-TKI therapy. To uncover the molecular mechanism of BC-mediated EGFR-TKI resistance in lung cancer, we screened and identified nucleolin and hnRNPK that interact with BC. BC formed the splicing complex with nucleolin and hnRNPK to facilitate the production of a non-protein-coding inositol monophosphatase domain containing 1 (IMPAD1) splice variant, instead of the protein-coding variant. The BC-mediated alternative splicing (AS) of IMPAD1 resulted in the induction of the epithelial-mesenchymal transition and resistance to EGFR-TKI in lung cancer. High BC expression correlated with clinical progress and poor survival among 402 patients with LUAD. DISSCUSSION: Through alternative splicing, BC boosted the non-coding IMPAD1-203 transcript variant while suppressing the IMPAD1-201 variant. In order to control the processing of pre-mRNA, BC not only attracted RNA binding proteins (NCL, IGF2BP1) or splicing factors (hnRNPK), but also controlled the formation of the splicing-regulator complex by creating RNA-RNA-duplexes. CONCLUSION: Our results reveal an important role for BC in mediating resistance to EGFR-targeted therapy in LUAD through IMPAD1 AS and in implication for the targeted therapy resistance.

[A systematic review and meta-analysis of randomized controlled trails : adjuvant interferon therapy for hepatocellular carcinoma].

OBJECTIVE: To evaluate the efficacy and safety of adjuvant interferon (IFN) therapy for viral hepatitis related hepatocellular carcinoma(HCC) after the treatment of resection, ablation or TACE. METHODS: PUBMED, EMBASE, Cochrane Library, CNKI, CBM, Wan fang Data were searched, plus some manual search and searching on the internet for grey literature. The studies that according to the standards were included, then Meta-analysis were done. RESULTS: Eight studies (n=857, 442 treated with IFN) were eligible for this study, pooled data showed benefit of IFN for the prevention of HCC recurrence, 1-year [RR=0.71, 95% CI (0.51, 0.99)], 3-year [RR=0.86, 95% CI (0.76-0.98)], 4-year [RR=0.79, 95% CI (0.68-0.91)]. IFN showed benefit for improving 1-year and 2-year survival, 1-year [RR=1.09, 95% CI (1.01-1.18)], 2-year [RR=1.25, 95% CI (1.04-1.50)]. The difference on 2-year, 5-year recurrence rate are without statistical significance, the same to 3-year, 4-year, 5-year survival rate. CONCLUSION: IFN therapy after the treatment of resection, ablation or TACE can probably reduce HCC recurrence rate and improve survival with acceptable toxicities.

Addition of thermal ablation to systemic chemotherapy for the treatment of unresectable intrahepatic cholangiocarcinoma: a propensity score matching analysis.

OBJECTIVES: To retrospectively compare the survival outcomes of thermal ablation plus chemotherapy to those of chemotherapy alone in patients with unresectable intrahepatic cholangiocarcinoma (ICC). METHODS: 189 patients with unresectable ICC who received thermal ablation plus chemotherapy or chemotherapy alone as the initial treatment were identified . To avoid potential bias, 1:1 matching between groups was performed through propensity score matching. Overall survival (OS) was the primary endpoint. Clinical and tumor factors related to OS were analyzed through univariate and multivariate analyses. RESULTS: Of the enrolled patients, 55 received ablation plus chemotherapy, and 134 received chemotherapy alone. The median OS was 16.267 months for patients treated with combined therapy and 6.067 months for patients treated with chemotherapy alone (p = 0.000). The benefit of ablation plus chemotherapy was also preserved in the matched cohort, with a median OS of 15.233 months in the combined treatment group and 7.967 months in the chemotherapy group (p = 0.009). Univariate and multivariate analyses indicated that the type of treatment was an independent factor of OS (p < 0.05). CONCLUSIONS: The combination of thermal ablation and systemic chemotherapy provides an opportunity to improve the prognosis of patients with unresectable ICC.

Predictive role of the monocyte-to-lymphocyte ratio in advanced hepatocellular carcinoma patients receiving anti-PD-1 therapy.

Background: The immune checkpoint inhibitor (ICIs) therapy has been proven effective in a range of solid tumors including hepatocellular carcinoma (HCC), non-small cell lung carcinoma and metastatic melanoma. However, only a subset of approximately 20% of patients shows an objective response to anti-PD-1 therapy in HCC. Furthermore, the response to anti-PD-1 therapy is not correlated with programmed cell death 1 ligand expression in tumor tissue. Therefore, it is urgent to identify a biomarker to predict the response of anti-PD-1 therapy. Methods: This retrospective study was conducted at the Fudan University Shanghai Cancer Center from December 2019 to June 2021. The monocyte-to-lymphocyte ratio (MLR) was analyzed using a receiver operating characteristic (ROC) curve. A Cox regression model and the log-rank test were used to analyze the relationship between the MLR value and the time to progression (TTP). Results: A total of 34 advanced HCC patients were enrolled in this study. The cut-off point for the MLR at baseline was 0.35. Univariate and multivariate Cox regression models showed that the MLR at baseline was significantly correlated with the TTP (P<0.05). Consistent results were found for disease progression. The log-rank test showed that patients in the low MLR group had a longer TTP (P=0.0027). At the time of disease progression, the median TTP in the low and high MLR groups were 33 and 18 weeks, respectively (P=0.0047). Conclusions: The MLR can predict the response to anti-PD-1 therapy, and a high MLR is correlated with a short TTP in anti-PD-1-treated HCC patients.

Combined ablation-chemotherapy versus chemotherapy alone for pancreatic cancer with liver metastasis: a propensity score matching study.

Objectives: To retrospectively assess the efficacy of combined ablation-chemotherapy in comparison to that of chemotherapy alone in patients with liver metastasized pancreatic ductal adenocarcinoma (lmPDAC).Methods: In total 104 patients with hepatic oligo metastasized PDAC were identified; among them, 74 patients underwent combined thermal ablation-chemotherapy, and 30 patients underwent chemotherapy alone. Through propensity score matching, 1:1 matching of the combined ablation-chemotherapy group and chemotherapy group was achieved. The primary endpoint of this study was overall survival (OS). Clinical and tumor-related factors affecting OS were also analyzed through univariate and multivariate analyses using the Cox risk model.Results: For patients treated with combined ablation-chemotherapy, the median OS was 10.77 months, while it was 5.77 months for patients treated with chemotherapy alone (P = 0.011). The survival benefit for patients treated with combined ablation-chemotherapy was still preserved in the matched cohort, with a median OS of 8.17 months compared to 5.77 months in the chemotherapy group. Univariate and multivariate analyses in the matched population also showed treatment with combined ablation-chemotherapy was an independent prognostic factor (P < 0.05).Conclusions: For patients with liver metastases from pancreatic cancer, the combined use of thermal ablation and systemic chemotherapy offers a chance for a better survival outcome.

A retrospective analysis of survival factors of high intensity focused ultrasound (HIFU) treatment for unresectable pancreatic cancer.

OBJECTIVE: To retrospectively evaluate possible impact factors of HIFU treatment outcome for unresectable pancreatic cancer patients. PATIENTS AND METHODS: A total of 689 patients with unresectable pancreatic cancer were recruited in our center from December 30, 2007 to January 30, 2015. 436 patients with unresectable pancreatic cancers received HIFU treatment; the other 253 patients received non-HIFU treatment. Among these 436 patients, 345 patients received a one-time HIFU treatment, 91 patients received HIFU treatment from 2 to 5 times in the same pancreatic mass; 89 patients received HIFU treatment alone; 347 patients received HIFU-based combined therapies. Complications and overall survivals (OS) data in each group were collected. RESULTS: The median overall survivals (mOS) in HIFU group and non-HIFU group were 7.1 vs. 5 months (P=0.005): 9.3 vs. 7.3 months (P=0.202) for patients with stage II disease, 8.3 vs. 7.3 months (P=0.783) for patients with stage III disease, and 6.4 vs. 4.2 months (P<0.0001) for patients with stage IV disease, respectively. Furthermore, there was a significant difference between repeated HIFU and one-time HIFU (mOS: 8.6 vs. 6.8 months, P=0.011). Time of HIFU treatment (P=0.0027), chemotherapy (P<0.0001), radiotherapy (P=0.0006), regional intra-arterial chemotherapy (RIAC) (P<0.0001), and stage (P<0.0001) were independent prognostic factors for the patients who received HIFU treatment. Cox analysis on the relative risk of prognostic factors showed that repeated HIFU vs. one-time HIFU (HR=0.729: 95% CI=0.576-0.924), chemotherapy vs. non-chemotherapy (HR=0.664: 95% CI=0.576-0.766), radiotherapy vs. non-radiotherapy (HR=0.580: 95% CI=0.427-0.789), RIAC vs. non-RIAC (HR=0.737: 95% CI=0.648-0.837), and stage (HR=1.386, 95% CI=1.187-1.619) were associated with significantly inferior survival. Overall, adverse events occurred in 23.2% (101/436) in the HIFU group, which included increase of serum or urinary amylase levels, incomplete intestinal obstruction, mild fever, etc. There were no severe adverse events such as skin burns or GI perforation related to HIFU therapy in any of the patients treated. CONCLUSION: This retrospective analysis revealed that the use of a multimodal treatment approach (the combined therapy of HIFU, RIAC, and chemotherapy, with or without radiotherapy) could improve survival of patients with unresectable pancreatic cancer, and repeated HIFU presented a survival benefit and did not increase risk.

Serum miR-224 reflects stage of hepatocellular carcinoma and predicts survival.

BACKGROUND: In our previous study, we conducted a systematic screening of miRNA to identify potential serum biomarkers for predicting venous metastasis and survival in patients with hepatocellular carcinoma (HCC). miR-224 was one of the differentially expressed miRNAs. This study aimed to confirm whether serum miR-224 level is associated with the presence of venous metastasis and survival. METHODS: TaqMan miRNA probe was used to perform qRT-PCR assays to evaluate the expression of serum miR-224 in a cohort of 182 HCC patients. RESULTS: Patients with high miR-224 serum level showed poor survival compared to that with low miR-224 serum level (HR 1.985; 95% CI, 1.08, 3.65, P=0.027). The serum miR-224 levels were significantly higher in the BCLC stage C patients compared with the stage B patients (P=0.005). In further analysis, significant difference of serum miR-224 expression level was observed when patients grouped by the status of PVTT but not the status of extra-liver metastasis (P=0.013 and P=0.091). Serum levels of miR-224 showed significant relation with parameters of liver damage and serum AFP. CONCLUSION: Serum miR-224 might be BCLC stage dependent. It can reflect the status of tumor and liver damage. It was an independent predictor for the survival of HCC patients.