Case report: Complete response after transcatheter arterial chemoembolization combined with donafenib plus tislelizumab therapy for hepatocellular carcinoma with main trunk portal vein tumor thrombus in a patient coinfected with HIV and HBV.

Background: Coinfection with the human immunodeficiency virus (HIV) and the hepatitis B virus (HBV) occurs in 5-67% of patients with HIV. HIV weakens the human immune system and leads to various tumors. Patients with unresectable hepatocellular carcinoma (HCC) and HIV experience poor treatment efficacy and have a short survival period. Approximately 70% of cases of HCC are diagnosed at advanced stages due to the subtle onset of the disease. As a result, most cases are not suits for curative therapy. Transcatheter arterial chemoembolization (TACE) is the first-line treatment for intermediate-stage HCC and is commonly used to treat unresectable HCC in China. Recent advancements in systemic treatments have significantly enhanced the effectiveness of unresectable HCC treatment. Several previous study showed that combination treatment combination therapy can enhance the efficacy. Notably, studies proposed that TACE combined targeted drugs with immune checkpoint inhibitors results in a high objective response rate and overall survival. However, the novelty of this study lies in its report of a complete response using a triple combination in patients with HIV and HCC with main trunk portal vein tumor thrombus. Case presentation: A 57-year-old woman was diagnosed with HCC with a main trunk portal vein tumor thrombus combined with HIV infection, cirrhosis, and chronic viral hepatitis. She underwent TACE and was administered donafenib and tislelizumab. This triple therapy treatment regimen resulted in a clinical complete response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) based on contrast-enhanced computed tomography. Conclusion: We first used TACE combined with donafenib and tislelizumab for HCC patients with main trunk portal vein tumor thrombus and HIV-HBV coinfection and achieved complete response.

Low expression of the ubiquitin ligase FBXW7 correlates with poor prognosis of patients with colorectal cancer.

FBXW7 is a potential tumor suppressor that regulates ubiquitination and proteolysis of multiple targets such as cyclin E, c-Myc, c-Jun and Notch. However, little knows about the correlation between FBXW7 and prognosis of patients with colorectal cancer (CRC). In this study, we detected FBXW7 expression in CRC tissue microarray which includes 568 cases cancer tissue and their paired adjacent non-cancerous tissues. We found that FBXW7 expression was significantly reduced in CRC tissues versus paired normal colon tissues (P < 0.001). Moreover, low FBXW7 expression was significantly associated with increased lymph node metastasis (P < 0.001) and advanced TNM stage (P < 0.001). Besides, the low expression of FBXW7 indicated the poor prognosis in CRC patients for both overall and disease-free cumulative survival (P < 0.001 and P = 0.003, respectively). Multivariate Cox regression analysis showed that low FBXW7 expression was an independent unfavorable prognostic factor of CRC (hazard ratio = 0.45, P = 0.001). In conclusion, we can indicate that FBXW7 may play essential roles in the progression of CRC and function as an independent prognostic marker for clinical diagnosis and therapy treatment of patients with CRC.

An insertion/deletion polymorphism within the promoter of EGLN2 is associated with susceptibility to colorectal cancer.

OBJECTIVE: To investigate the association between susceptibility to colorectal cancer (CRC) and a 4-bp insertion/deletion polymorphism (rs10680577) in the proximal promoter of the EGLN2 gene. METHOD: The first step in genotyping EGLN2 was PCR, then the PCR products were separated using 7% nondenaturing polyacrylamide gel electrophoresis and visualized by silver staining according to the final product band location and quantity to determine the genotype of the sample. The final count was done by two different pathologists. RESULT: In the codominant model, compared with the ins/ins genotype, subjects with the heterozygous ins/del or homozygous del/del genotype had a significantly increased risk of CRC (adjusted OR = 1.45, p<0.0001 and OR = 2.44, p = 0.0001, respectively). Each additional copy of the 4-bp deletion allele conferred a significantly increased risk of CRC (OR = 1.47, 95% CI 1.28-1.66, p<0.0001). In the stratification analysis, we further proved that the association was more prominent in TNM stage III and IV cancer compared with stage I and II (adjusted OR = 1.43, 95% CI 1.07-1.93, p for heterogeneity = 0.02). CONCLUSIONS: Our study provided initial evidence that the insertion/deletion polymorphism rs10680577 may play a functional role in the development of CRC in the Chinese population.

The appearance of Tregs in cancer nest is a promising independent risk factor in colon cancer.

PURPOSE: To investigate the prognostic value of tumor-infiltrating regulatory T cells (Tregs) in the distribution of cancer nest, cancer stroma and normal mucosa and FOXP3-positive cancer cells in colon cancer patients after resection. METHODS: Paraffin blocks of operation resection of primary adenocarcinoma of colon were obtained from ninety patients. The distribution of tumor-infiltrating Tregs was detected by tissue microarray and immunohistochemistry staining technique to evaluate the prognostic effects by Kaplan-Meier and Cox regression analysis using median values as cutoff. RESULTS: The intratumoral Tregs counts were significantly higher than that in corresponding normal mucosa tissues (P < 0.001); the Tregs counts in cancer nest were significantly lower than that in corresponding cancer stroma tissues (P < 0.001); the increased intratumoral Tregs counts were associated with favorable prognosis (P < 0.05); the presence of Tregs in cancer nest was associated with unfavorable prognosis and was an independent prognostic factor for overall survival (P < 0.05). The appearance of FOXP3-positive cancer cells was associated with worse prognosis (P < 0.05). In addition, the frequency of the presence of FOXP3-positive cancer cells was higher in patients with lymphatic invasion (P < 0.001) and lower in patients with early TNM stage (P < 0.01). CONCLUSIONS: The higher tumor-infiltrating Tregs counts are closely associated with the improved prognostic effects of colon carcinoma. Tregs play different roles in cancer nest and cancer stroma. And the appearance of Tregs in cancer nest is a promising independent risk factor for overall survival in colon carcinoma. FOXP3-positive cancer cells may also be a risk factor for overall survival in colon carcinoma.