LncRNA HOXB-AS3 Promotes Proliferation, Migration, Invasion, and Epithelial-Mesenchymal Transition of Gallbladder Cancer Cells by Activating the MEK/ERK Pathway

OBJECTIVE: Long non-coding RNA HOXB-AS3 has been implicated in tumor progression in a variety of carcinomas. However, its biological role in gallbladder cancer (GBC) is unknown. The biological function and underlying mechanism of the lncRNA HOXB-AS3 for GBC were investigated in this study.MATERIALS AND METHODS: To investigate the function of lncRNA HOXB-AS3 in GBC, the level of lncRNA HOXB-AS3 in GBC cells was detected by quantitative reverse-transcription polymerase chain reaction. The cell viability was tested by cell counting kit-8 assay and colony formation assay. Flow cytometry was performed to investigate cell apoptosis and cell cycle. In addition, cell migration ability was assessed by wound healing assay and cell invasion ability by transwell invasion assay. RESULTS: It was found that HOXB-AS3 was obviously elevated in GBC tissues and cells. However, inhibition of HOXB-AS3 could depress NOZ and GBC-SD cell viability as well as induce cell apoptosis. Also, the gallbladder cancer cell cycle was blocked in the G1 phase. Meanwhile, NOZ and GBC-SD cell migration, invasion, and epithelial-mesenchymal transition were obviously suppressed by knockdown of HOXB-AS3. What is more, we found that HOXB-AS3 might promote gallbladder progress by activating the MEK/ERK pathway.CONCLUSION: The results show that lncRNA HOXB-AS3 serves as a key regulator in GBC progression, which provides a new treatment strategy for GBC.

Arsenic Induced Gallbladder Cancer Risk in Eastern Part of Indo-Gangetic Plains

BackgroundIn recent times Gallbladder cancer (GBC) incidences increased many folds in India. Majority of GBC cases are being reported from arsenic hotspots identified in Bihar. MethodsIn this prospective study volunteers were selected who underwent surgery in our cancer institute. There were 11 control benign gallbladder cases and 28 confirmed gallbladder cancer cases. Their biological samples such as blood, gallbladder tissue, gallbladder stone, bile and hair samples were collected for arsenic estimation. Moreover, n=512 gallbladder cancer patients blood samples were evaluated for the presence of arsenic to understand exposure level in the population. ResultsA significantly high arsenic concentration (p<0.05) was detected in the blood samples, gallbladder tissue, gallstones, bile and hair samples in comparison to the control group. Moreover, n=512 blood samples of GBC patients had significantly very high arsenic concentration. ConclusionsThe study shows very high arsenic concentration observed in the blood, gallbladder tissue, gallbladder stone, bile and hair samples in GBC cases in comparison to the benign control cases indicates the correlation between chronic arsenic exposure and gallbladder cancer incidences in eastern Indo-Gangetic plains region. The study also makes an attempt to establish the likely correlation/association between arsenic exposure and gallbladder cancer disease.

Case Report: Addition of PD-1 Antibody Camrelizumab Overcame Resistance to Trastuzumab Plus Chemotherapy in a HER2-Positive, Metastatic Gallbladder Cancer Patient

HER2 amplification/overexpression is a common driver in a variety of cancers including gallbladder cancer (GBC). For patients with metastatic GBC, chemotherapy remains the standard of care with limited efficacy. The combination of HER2 antibody trastuzumab plus chemotherapy is the frontline treatment option for patients with HER2-positive breast cancer and gastric cancer. Recently, this regime also showed antitumor activity in HER2-positive GBC. However, resistance to this regime represents a clinical challenge. Camrelizumab is a novel PD-1 antibody approved for Hodgkin lymphoma and hepatocellular carcinoma in China. In this study, we presented a HER2-positive metastatic GBC patient who was refractory to trastuzumab plus chemotherapy but experienced significant clinical benefit after the addition of camrelizumab. Our case highlights the potential of immunotherapy in combination with HER2-targeted therapy in HER2-positive GBC. We also demonstrated that two immune-related adverse events (irAEs) associated with camrelizumab can be managed with an anti-VEGF agent apatinib. This case not only highlights the importance of irAE management in patients treated with camrelizumab, but also demonstrates the potential of PD-1 antibody plus trastuzumab in HER2-positive GBC patients who have developed resistance to chemotherapy and trastuzumab-based targeted therapy.

Meta-analysis of the diagnostic performance of serum carbohydrate antigen 19-9 for the detection of gallbladder cancer

Introduction Carbohydrate antigen 19-9 (CA19-9) is a well-studied tumor marker, yet its diagnostic value for gallbladder cancer remains unclear. The present meta-analysis was conducted to validate the role of serum CA19-9 for the detection of gallbladder cancer. Methods A systematic search of digital databases was conducted, complemented by additional hand-searching. Studies that reported serum CA19-9 for the differentiation of gallbladder cancer cases from non-gallbladder cancer controls were considered eligible. Results A total of 27 studies involving 4300 subjects were included. The pooled sensitivity, specificity, and area under the curve in diagnosing gallbladder cancer were 0.70 (95% confidence interval (CI): 0.63–0.76), 0.92 (95% CI: 0.88–0.94), and 0.89 (95% CI: 0.86–0.92), respectively. The pooled positive likelihood rate, negative likelihood rate, and diagnostic odds rate were 8.30 (95% CI: 5.84–11.69), 0.33 (95% CI: 0.27–0.41), and 25.13 (95% CI: 5.83–39.89), respectively. Meta-regression analysis revealed that there was significantly lower sensitivity (0.69, 95% CI: 0.61–0.77) and specificity (0.91, 95% CI: 0.87–0.95) when CA19-9 was used for the differentiation of gallbladder cancer cases from benign biliary diseases. A better specificity of 0.93 (95% CI: 0.90–0.96) was reached in the setting of a sample size ≥100. Conclusions Serum CA19-9 can be a potential candidate marker for the detection of gallbladder cancer, which maintains moderate sensitivity and good specificity. Attention should be paid to the control type and sample size, which may affect its diagnostic accuracy. Also, results should be interpreted with caution due to significant heterogeneity primarily caused by different thresholds between included studies.

Examination of The Characteristics of Long-Term Survivors Among Patients With Gallbladder Cancer With Liver Metastasis Who Underwent Surgical Treatment: A Retrospective Multicenter Study (ACRoS1406)

Background: Gallbladder cancer (GBC) with liver metastasis is considered unresectable. However, there have been infrequent reports of long-term survival in patients with GBC and liver metastases. Therefore, we examined the characteristics of long-term survivors of gallbladder cancer with liver metastasis.Methods: A retrospective multicenter study of 503 patients with GBC (mean age, 68.6 years; female, 52%) was performed. Although patients with pre-operatively diagnosed GBC and liver metastasis were generally excluded from resection, some cases identified during surgery were resected.Result: In patients with resected stage III/IV GBC (n = 228), the period 2007–2013 (vs. 2000–2006, hazard ratio 0.55), other type histology (vs. well/moderate histology, hazard ratio 2.34), ≥2 liver metastases (vs. one liver metastasis, hazard ratio 4.30), and positive margin resection (vs. complete resection with a negative margin, hazard ratio 1.57) were independent prognostic factors for overall survival, whereas one liver metastasis (vs. no liver metastasis) was not. The 5-year overall survival and median survival times in those with one liver metastasis with complete resection and a negative margin (40.9%, 28.3 months) were significantly better than those in patients with ≥2 liver metastases with complete resection and a negative margin (0%, 11.0 months, p = 0.025), and comparable to those in patients with liver metastasis with complete resection and a negative margin (37.0%, 33.0 months). According to the univariate analysis of resected patients with GBC and liver metastases (n=24), minor hepatectomy, less blood loss, less surgery time, papillary adenocarcinoma, T2, morbidity of Clavien–Dindo classification ≤ 2, and adjuvant chemotherapy were significantly associated with longer survival. Long-term survivors (n = 5) had a high frequency of T2 tumors (4/5), had small liver metastases near the gallbladder during or after surgery, underwent minor hepatectomy without post-operative complications, and received post-operative adjuvant chemotherapy.Conclusions: Although there is no surgical indication for GBC with liver metastasis diagnosed pre-operatively, minor hepatectomy and post-operative chemotherapy may be an option for selected patients with T2 GBC and liver metastasis identified during or after surgery who do not have other poor prognostic factors.