Infectious Agents and Cancer

The most common cancer worldwide among women is breast cancer. The initiation, promotion, and progression of this cancer result from both internal and external factors. The International Agency for Research on Cancer stated that 18-20% of cancers are linked to infection, and the list of definite, probable, and possible carcinogenic agents is growing each year. Among them, biological carcinogens play a significant role. In this review, data covering infection-associated breast and lung cancers are discussed and presented as possible involvements as pathogens in cancer. Because carcinogenesis is a multistep process with several contributing factors, we evaluated to what extent infection is significant, and concluded that members of the herpesvirus, polyomavirus, papillomavirus, and retrovirus families definitely associate with breast cancer. Detailed studies of viral mechanisms support this conclusion, but have presented problems with experimental settings. It is apparent that more effort needs to be devoted to assessing the role of these viruses in carcinogenesis, by characterizing additional confounding and synergistic effects of carcinogenic factors. We propose that preventing and treating infections may possibly stop or even eliminate certain types of cancers.

Đây là báo cáo về các hoạt động nghiên cứu hiện đang diễn ra trong lĩnh vực virus học, ung thư học và ung thư liên quan đến virus cũng như các khả năng điều trị và phòng ngừa thông qua vaccine và liệu pháp miễn dịch, như đã được trình bày tại hội thảo "Nhiễm virus mạn tính và ung thư, cơ hội cho vaccine" diễn ra trực tuyến vào ngày 16-17 tháng 12 năm 2021. Các chuyên gia từ nhiều lĩnh vực liên quan đến nghiên cứu mối quan hệ phức tạp giữa các khối u đặc và virus đã gặp gỡ để thảo luận về những phát triển gần đây trong lĩnh vực này và báo cáo những đóng góp cá nhân của họ cho các chủ đề đã nêu. Mục tiêu thứ cấp là duy trì Mạng lưới TECHVAC được thành lập vào năm 2016 như một nhóm công tác đa lĩnh vực chuyên biệt dành riêng cho việc phát triển vaccine và liệu pháp miễn dịch chống lại các nhiễm trùng virus mạn tính và các loại ung thư liên quan, với mục đích xác định các lĩnh vực quan tâm chung, thúc đẩy hợp tác nghiên cứu, thiết lập các chương trình và dự án hợp tác xuyên biên giới, cũng như phối hợp các hoạt động lâm sàng và nghiên cứu.

Mucosa-associated lymphoid tissue (MALT) lymphoma is generally associated with chronic antigen stimulation: auto-antigens or of microbial origin. Only one study suggested association between Achromobacter xylosoxidans and pulmonary MALT lymphoma. We aimed to investigate the presence of virus or any infectious agents in pulmonary MALT lymphoma by using metagenomic next-generation sequencing (mNGS). All lung samples were centrally reviewed. The t(11;18) (q21;q21) was evaluated by FISH analysis. The snap frozen large lung biopsies were analyzed by mNGS. After lung biopsies homogenization total nucleic acids (RNA and DNA) were extracted, amplified and classified according to their taxonomic assignment, after exclusion of host DNA. We included 13 samples from pulmonary MALT lymphoma (mean age: 60.3 years, 7 women, 3 with auto-immune background) and 10 controls. The diagnosis of MALT lymphoma was confirmed for the 13 samples, 3 showed API2-MALT1 translocation (23%). No evidence of the presence of a specific pathogen was clearly identified in the group of patients with pulmonary MALT lymphoma. We identifiedA. xylosoxidans sequence in 4/13 patients and in 4/10 controls. This study did not find evidence for a DNA or RNA virus, a fungi, a parasite or a bacteria associated with pulmonary MALT lymphoma either in the stroma or in tumor cells.

Epigenetic mechanisms are hypothesized to contribute substantially to the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer, although empirical data are limited. Women (n = 419) were enrolled at colposcopic evaluation at Duke Medical Center in Durham, North Carolina. Human papillomavirus (HPV) was genotyped by HPV linear array and CIN grade was ascertained by biopsy pathologic review. DNA methylation was measured at differentially methylated regions (DMRs) regulating genomic imprinting of the IGF2/H19, IGF2AS, MESTIT1/MEST, MEG3, PLAGL1/HYMAI, KvDMR and PEG10, PEG3 imprinted domains, using Sequenom-EpiTYPER assays. Logistic regression models were used to evaluate the associations between HPV infection, DMR methylation and CIN risk overall and by race. Of the 419 participants, 20 had CIN3+, 52 had CIN2, and 347 had ≤ CIN1 (CIN1 and negative histology). The median participant age was 28.6 (IQR:11.6) and 40% were African American. Overall, we found no statistically significant association between altered methylation in selected DMRs and CIN2+ compared to ≤CIN1. Similarly, there was no significant association between DMR methylation and CIN3+ compared to ≤CIN2. Restricting the outcome to CIN2+ cases that were HR-HPV positive and p16 staining positive, we found a significant association with PEG3 DMR methylation (OR: 1.56 95% CI: 1.03–2.36). While the small number of high-grade CIN cases limit inferences, our findings suggest an association between altered DNA methylation at regulatory regions of PEG3 and high grade CIN in high-risk HPV positive cases.

To compare liver-specific EOB-GD-DTPA and liver-non-specific Gd-BT-DO3A MR, in hepatocellular carcinoma (HCC) and liver colorectal metastases. Seventy HCC patients with 158 nodules and 90 colorectal liver metastases (mCRC) with 370 lesions were included in the retrospective analysis. HCC patients underwent MR at 0 time (MR0), after 3 (MR3) and 6 months (MR6) using two different CM; 69 mCRC patients underwent MR with Gd-EOB-BTPA and 21 mCRC patients with Gd-BT-DO3A. We evaluated arterial phase hyperenhancement, lesion-to-liver contrast during portal phase, hepatobiliary phase parenchymal hyperenhancement. In HCC patients arterial phase hyperenhancement degree was statistically higher (p = 0.03) with Gd-BT-DO3A (mean 4) than GD-EOB-DTPA (mean 2.6), while we found no significant statistical differences among mean (2.6) values at MR0 and MR6 using GD-EOB-DTPA. For all 209 patients underwent Gd-EOB-DTPA, we found that lesion-to-liver contrast during portal phase mean value was 4 while for patients underwent MR with Gd-BT-DO3A was 3 (p = 0.04). For HCC hepatobiliary phase parenchymal hyperenhancement mean value was 2.4. For mCRC patients: among 63 patients underwent previous chemotherapy hepatobiliary phase parenchymal hyperenhancement mean value was 3.1 while for 6 patients no underwent previous chemotherapy was 4 (p = 0.05). Gd-EOB-DTPA should be chosen in pre surgical setting in patients with colorectal liver metastases.

Aberrant glycosylation is a characteristic of tumour cells. The expression of certain glycan structures has been associated with poor prognosis. In cervical carcinoma, changes in the expression levels of some glycogenes have been associated with lymph invasion. Human papillomavirus (HPV) infection is one of the most important factors underlying the development of cervical cancer. The HPV oncoproteins E6 and E7 have been implicated in cervical carcinogenesis and can modify the host gene expression profile. The roles of these oncoproteins in glycosylation changes have not been previously reported. To determine the effect of the E6 and E7 oncoproteins on glycogene expression we partially silenced the E6 and E7 oncogenes in HeLa cells, we performed a microarray expression assay to identify altered glycogenes and quantified the mRNA levels of glycogenes by RT-qPCR. A protein-protein interaction network was constructed to identify potentially altered glycosylation pathways. The microarray analysis showed 9 glycogenes that were upregulated and 7 glycogenes that were downregulated in HeLa shE6/E7 cells. Some of these genes participate in glycosylation related to Notch proteins and O-glycans antigens. Our results support that E6 and E7 oncoproteins could modify glycogene expression the products of which participate in the synthesis of structures implicated in proliferation, adhesion and apoptosis.

Glutamyl-prolyl-tRNA synthetase 1 (EPRS1) is an aminoacyl-tRNA synthase involved in the pathology of cancer and other diseases. In this study, we investigated the carcinogenic function, potential mechanism, and clinical significance of EPRS1 in human hepatocellular carcinoma (HCC). The expression, clinical significance, and prognostic value of EPRS1 in HCC were assessed using the TCGA and GEO databases. The function of EPRS1 in HCC cells was detected by CCK-8, Transwell, and hepatosphere formation assays. Immunohistochemistry was used to explore the difference in EPRS1 levels in HCC tissues and peri-cancerous tissues. The mechanism of EPRS1 was studied using a proteomics method. Finally, cBioportal and MEXEPRSS were used to analyze the variations involved in the differential expression of EPRS1. EPRS1 was frequently upregulated at the mRNA and protein levels in liver cancer. Increased EPRS1 correlated with shortened patient survival. EPRS1 could promote cancer cell proliferation, characteristics of cell stemness, and mobility. Mechanistically, EPRS1 played a carcinogenic role by upregulating several downstream proline-rich proteins, primarily LAMC1 and CCNB1. In addition, copy number variation could contribute to the high expression of EPRS1 in liver cancer. Together, our data imply that enhanced EPRS1 contributes to the development of HCC by increasing the expression of oncogenes in the tumor microenvironment. EPRS1 may be a successful treatment target.