Advances in cancer biology - metastasis最新文献

Background

In our study, we examined the 5-year survival of OSCC patients with HPV positive or negative status along with p16 protein expression.

Method

A total of 72 biopsy tissue specimens from histologically confirmed oral squamous cell carcinoma (OSCC) patients were collected. HPV detection and genotyping were performed using HPV E6/E7 and HPV- type-specific multiplex primer for nested-PCR. Immunohistochemistry evaluation of pl6 was conducted. SPSS statistical software (ver 20) was used for data analysis.

Results

High risk-HPV (hr-HPV) DNA positivity was found in 27.7% (n = 20) of OSCC patients. Stage III OSCC patients were 7.80 times more likely to survive 5 years than stage IV patients (OR-7.80 CI-95%; P-0.03). Among the hr-HPV positive OSCC patients, we found that the median survival time for the 1st year (95%), 3 years (78.5%), and 5 years (38.5%) was significantly higher than that of the hr-HPV negative [1st year (78.6%), 3 years (45.2%) and 5 years (38.5%)] OSCC patients (P-0.03 The survival of male patients with hr-HPV positive OSCC is 9.75 times greater than the survival of patients with HPV negative OSCC (OR-9.75; CI-95%; P-0.05). The p16 expression level (low to overexpression) group and negative P16 expression group of OSCC patients have not demonstrated a significant association with 5-year survival.

Conclusion

We conclude that in OSCC cases of North-East India, the presence of hr-HPV in OSCC cases could be a good predictor of 5-year survival rate. Expression of p16 does not appear to have any significant association with 5-year survival.

Small cell lung cancer (SCLC) is characterized by early metastatic dissemination and rapid emergence of chemoresistance resulting in a very dismal prognosis. SCLC tumors are characterized by nearly universal biallelic inactivation of TP53 and RB1 genes and are classified into four molecular subtypes based on the expression of lineage-specific transcription factors. The integration of information encoded by the coding and non-coding genome has significantly improved our understanding of the contribution of various non-coding RNAs (ncRNAs), such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), in the pathogenesis of SCLC. This has led to the concept of competing endogenous RNAs (ceRNAs) where the presence of the same miRNA response elements in one or more coding and ncRNAs may result in them competing for the same miRNA. Several studies have looked at the role of lncRNAs and circRNAs as ceRNAs by constructing ceRNA regulatory networks (ceRNETs). In this review, we discuss the role of ceRNETs in regulating various cancer hallmarks, including cell proliferation, invasion, migration, EMT, apoptosis, and chemoresistance of SCLC cells. We also discuss the potential of lncRNAs and circRNAs as biomarkers for diagnosis, prognosis, and predicting chemoresistance of SCLC.

Following the declaration of COVID-19 as a pandemic in February 2020, one of the most important public health impacts was the decrease in demand for screening mammography, with a consequent impact on the early diagnosis of breast cancer. Therefore, the aim of this study was to compare the initial clinical staging of women with breast cancer in the pre-pandemic and pandemic periods at a reference cancer hospital in southern Brazil. We performed a retrospective cross-sectional study with a database of surgical procedures on the female breast, comparing the years 2019 and 2020. A total of 1733 surgical procedures for diagnostic and curative purposes were evaluated. Among these patients, 491 (49.2 %) were diagnosed with breast cancer in 2019 and 335 (45.5 %) in 2020. We excluded 907 patients due to benign diagnoses, carcinoma in situ, recurrence, presence of metastases, missing data, and other findings. When comparing 2019 and 2020, we found no significant difference in clinical staging or tumor phenotype. The median time in days between mammography and first treatment was also similar in both years. However, we observed a higher frequency of lobular histologies and neoadjuvant therapy as first treatment choice in the pandemic year. In conclusion, there was no significant difference in clinical staging between women diagnosed with breast cancer before and during the pandemic.

A significant obstacle to treating cancer is multidrug resistance (MDR), which is the capacity of cancerous cells to develop resistance to both traditional and cutting-edge chemotherapeutic treatments. Following the initial discovery that cellular pumps reliant on ATP were the root of chemotherapy resistance, more research has revealed the involvement of additional mechanisms, including increased drug metabolism, reduced drug entry, and compromised apoptotic pathways. Numerous projects have focused on MDR, and innumerable research has been conducted to better understand MDR and develop methods to mitigate its consequences. Multidrug resistance (MDR) is a key challenge in treating cancer. 90% of cancer-related fatalities are brought on by tumor metastasis and recurrence, which is possible with MDR. Drug resistance in cancerous cells is influenced by diverse internal and extrinsic variables, including genetic and epigenetic changes, drug efflux systems, DNA repair mechanisms, apoptosis, and autophagy. In this review paper, we list the potential hazards associated with cancer therapy in general, primarily multidrug resistance developing a theory for colorectal cancer in particular. We discussed the unique instance of multidrug resistance in colorectal cancer in malignancies generally and 5-fluorouracil, curcumin, and lipids as viable therapy options for the condition. The use of nanotechnology (mainly nanoparticles) has facilitated better in vitro as well as in vivo efficacy during preclinical phases, summarized below, allowing for a more thorough investigation of colorectal cancers and pancreatic carcinomas with their translation to following clinical trials.

The breast cancer scenario now requires new solutions for diagnosis and follow-up. The neutrophil-to-lymphocyte ratio (NLR) has been studied as a possible biomarker for predicting prognosis in solid tumors. Due to the ease of obtaining these values from a blood count, NLR could be useful in clinical practice. Therefore, the aim of this study was to analyze the relation between NLR and pathologic complete response (PCR) in breast cancer patients undergoing neoadjuvant treatment. We performed a cross-sectional retrospective study, including ductal breast cancer patients who underwent neoadjuvant chemotherapy and surgery between 2017 and 2019 at the reference hospital institution (n = 1230). Our data were obtained from medical records and laboratory results, so the study was approved by the research ethics committee of the data-providing hospital. Inclusion and exclusion criteria resulted in a final sample of 114 patients. The area under the curve (ROC) showed no statistically significant area (AUC = 0.546) with a CI95% = 0.417–0.676. No relation between NLR and PCR was observed (p = 0.631), indicating that NLR is not a good biomarker for PCR in this population. Regarding the pattern of NLR for different molecular subtypes, no statistical relation was found (p = 0.929). Thus, our study supports the literature that suggests there is no relationship between NLR and PCR.

Background

Manifestation of epithelial-to-mesenchymal transition (EMT) program in tumor cells is associated with the occurrence of multiple intermediate phenotypic states namely epithelial (E), mesenchymal (M) and hybrid E/M across the epithelial-mesenchymal spectrum and these states exhibit different invasive properties. Understanding the cellular and molecular mechanisms defining the E/M hybrid state of the cells during bladder tumor development may significantly aid in the identification of novel diagnostic and prognostic markers.

Materials and methods

The present study is taken up to identify hybrid E/M score based on the immunohistochemical localization and surface expressions of epithelial proteins [E-cadherin and Beta-catenin] and mesenchymal marker proteins [N-cadherin and Vimentin] on formalin fixed paraffin embedded tumor sections of the prospective series of 99 non-muscle invasive bladder cancer (NMIBC) and 87 muscle invasive bladder cancer (MIBC) patients. E/M score was then statistically examined with patients’ demographics to assess its potential in the diagnosis and prognosis of UCB patients.

Results

Among the E (E-cadherin^high, β-catenin^high), hybrid E/M (E-cadherin^low, β-catenin^low, N- cadherin^high and Vimentin^high) and M (N-cadherin^high and Vimentin^high) phenotypes, E/M phenotype was observed to be more prevalent in MIBC compared to E phenotype in NMIBC subtype. The current study reports the statistical association of tumor stage and tumor grade with the hybrid E/M state of urothelial tumor cells across both the subtypes. Hybrid E/M phenotype in MIBC patients was significantly shown to lower the overall survival time period compared to NMIBC patients. This supports the contribution of hybrid E/M state of tumor cells to the.

aggressiveness of the disease.

Conclusions

Characterizing the hybrid E/M state instead of all or none phenotype becomes an imperative to understand the dynamics of EMT and MET in the tumor pathophysiology of NMIBC and MIBC subtypes, and could contribute to better patient stratification and therapeutic strategies.

Triple-negative breast cancer (TNBC), which accounts for approximately 15–20% of all breast cancers, defined as lack of expression of estrogen receptor, progesterone receptor and Her-2 neu receptors. TNBC has two subtypes basal like and non-basal like, the former characterised by aggressive biology with limited therapeutic options. This study explored molecular markers involved in pathogenesis of TNBC and investigated novel potential diagnostic and therapeutic targets by CGH array and transcriptome array. aCGH analysis in TNBC demonstrated genes amplified were 3888, number of pathway hits was 1554 and major pathways amplified was found to be WNT signalling pathway and Cadherin signalling pathway. Among all metastatic sites and remission, activation of WNT signalling pathway is commonly observed. TNBC exhibited 1486 copy number variations (CNVR) which is approximately 250 times higher than controls. More than 20 CNVR was observed in all chromosomes and more than 80 CNVR was observed in Chr 1 to Chr 4, Chr 7, Chr 11 and Chr X. Common CNVR associated with amplified regions in Chr 22, Chr 14, Chr 8 and Chr 2 was observed in TNBC and CNVR associated with Chr 22q11.22–23, Chr 6p21.32–33, Chr11q12.2, Chr14q32.22–23, Chr 8p11.22–23, was observed in metastatic disease. In transcriptome array analysis a total of 11,359 differentially expressed genes with fold change 2.0 were in observed in TNBC comprise of 7639 upregulated genes and 3720 downregulated genes. Further, with fold change 10, 1526 upregulated genes and 839 down regulated genes were identified. Panther pathway analysis identified the main pathways of upregulated genes were Wnt signalling pathway, Integrin signalling pathway and Cadherin signalling pathway. The main pathways of down regulated genes were Inflammation mediated by chemokine and cytokine signalling pathways. PPI network shows that COL12A1, COL6A3, FN1, MMP3, WNT5A were key upregulated genes and ITGB7, PTPRC, ITGA4, LCK and CD247 were key down regulated genes. Cytoscape analysis followed by multiple list comparator tool identified top 5 significant hub genes were FN1, MMP3, COLL11A1, COL12A1 and COL3A1. The significant pathway genes obtained by CGH array and transcriptome array when compared, exhibited 5 common genes COL4A1, FN1, COL6A3, COL5A2 and PCDH7. These genes were not overexpressed in Controls and therefore involved in pathogenesis of TNBC. Expressions of these genes were validated by studying protein expression by immunohistochemistry. FN1 and COL6A3 protein over expression predicted worse DFS in TNBC and can be considered as therapeutic targets at diagnosis to reduce the disease metastases. These findings provide new insights into the pathogenesis of TNBC and guide for selection of targets related to diagnosis, prognosis and prediction of treatment in TNBC.

Endometrial cancer (EC) is the most common gynecological cancer, with rising mortality rates. Targeting non-coding RNAs (ncRNAs) to diagnose and cure endometrial cancer has shown both promise and limitations in recent studies. In comparison to normal tissues, LncRNAs are differentially expressed in ECs, and their dysregulation has been associated to tumor grade, lymph node metastasis, depth of myometrial invasion, FIGO stage and patient survival. Oncogenic lncRNAs (CCAT2, BANCR, NEAT1, MALAT1, LINP1, SRA and LSINCT5) and tumor suppressor lncRNAs (GAS5, MEG3, OIP5-AS1, FER1L4, and LINC00672) have been identified as downstream effectors or upstream modulators of important signaling pathways driving EC metastasis, including the PTEN/PI3K/AKT/mTOR, RAS/RAF/MEK/ERK, WNT/β-catenin, and p53 signaling pathways. Short non-coding RNAs called miRNAs also effect expression of genes at the post-transcriptional level. Multiple studies have shown that miRNAs play a critical role in the regulation of EC. We present a review of ncRNA expression patterns, prognostic significance, biological function and roles in the tumor microenvironment in EC cells in EC associated pathways. We also discuss how ncRNAs can be used as biomarkers for EC diagnosis and as potential therapeutic targets for different EC subtypes based on their ncRNA signature.

Cancer immune evasion is one of the principal mechanisms leading to the progression and metastatization of the disease. Despite the migration and infiltration at the tumor site of immune cells, multiple factors can influence the composition of hot or “immune-sensitive” tumors and cold or “immune-resistant” tumors. Among the multiple mechanisms responsible for the make-up of the tumor microenvironment are the expression levels of major histocompatibility molecules (MHC) and of the antigen processing machinery, the metabolic network, hypoxia, and the secretion of pro-inflammatory molecules (e.g., cytokines, chemokines, and growth factors). Moreover, the different triggered pathways can mediate the reprogramming of activated, memory, effector, or regulatory/tolerogenic subtypes of immune cells (T, NK, dendritic cells, and macrophages). Recent studies have focused on the role of cancer metabolism in evading immune surveillance through the action of the active tryptophan catabolic enzyme indoleamine 2,3-dioxygenase (IDO). Immune suppression and evasion mechanisms in cancer cells are now being extensively studied with a special focus on developing immunotherapy strategies, such as the targeting of immune checkpoints (programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1), Cytotoxic T-lymphocyte antigen-4 (CTLA-4)), adoptive cell therapy or cancer vaccines. In this review, an overview of the underlying mechanisms of cancer immune evasion and the efficacy of the therapeutic targets and agents to overcome the immune escape are described.