miRNAs作为癌症预测和预后标志物的巨大潜能

"因为不同癌症疗法对不同亚型患者有效,所以急需新型预测和预后标志物来提高癌症患者的疗效." miRNAs作为细胞通路的重要调控因子,在癌变过程中起着关键作用.最近研究已鉴定出许多潜在癌症标志物的miRNAs,部分miRNAs起癌基因、抑癌基因或转移调节因子的作用.因为不同癌症疗法对不同亚型患者有效,所以急需新型预测和预后标志物来提高癌症患者的疗效[1].     

Human Epididymis Protein 4 Reference Intervals in a Multiethnic Asian Women Population

Background: Ovarian cancer is ranked as the fifth most common cause of cancer death in women. In Malaysia,it is the fourth most common cancer in females. CA125 has been the tumor marker of choice in ovarian cancer butits diagnostic specificity in early stages is only 50%. Hence, there is a critical need to identify an alternative tumormarker that is capable of detecting detect ovarian cancer at an early stage. HE4 is a new tumor marker proposedfor the early diagnosis of ovarian cancer and disease recurrence. Currently, none of the normal ranges of HE4quoted in the literature are based on data for a multiethnic Asian population. Therefore, the aim of this studywas to determine reference intervals for HE4 in an Asian population presenting in University Malaya MedicalCentre, a tertiary reference hospital. Materials and Methods: 300 healthy women were recruited comprising150 premenopausal and 150 postmenopausal women, aged from 20-76 years. All women were subjected to apelvic ultrasonograph and were confirmed to be free from ovarian pathology on recruitment. Serum HE4 levelswere determined by chemiluminescent microparticle immunoassay (CMIA, Abbott Architect). The referenceintervals were determined following CLSI guidelines (C28-A2) using a non-parametric method. Results: Theupper limits of the 95th percentile reference interval (90%CI) for all the women collectively were 64.6 pmol/L,and 58.4 pmol/L for premenopausal) and 69.0 pmol/L for postmenopausal. The concentration of HE4 was notedto increase with age especially in women who were more than 50 years old. We also noted that our proposedreference limit was lower compared to the level given by manufacturer Abbott Architect HE4 kit insert (58.4vs 70 pmol/L for premenopausal group and 69.0 vs 140 pmol/L in the postmenopausal group). The study alsoshowed a significant difference in HE4 concentrations between ethnic groups (Malays and Indians). The levels ofHE4 in Indians appeared higher than in Malays (p<0.05), while no significant differences were noted between theMalays and Chinese ethnic groups. Conclusions: More data are needed to establish a reference interval that willbetter represent the multiethnic Malaysian population. Probably a larger sampling size of equal representationof the Malay, Chinese, Indians as well as the other native ethnic communities will give us a greater confidenceon whether genetics plays a role in reference interval determination.     

Saliva as a Potential Diagnostic Tool to Evaluate Relationship between Oral Microbiome and Potentially Malignant Disorders for Prevention of Malignant Transformation

Objective: The current research was conducted with an aim to assess the association of oral microbiome with Potentially malignant disorders (PMDs) because usage of tobacco in any form alters the normal microbiome and shifts it towards dysbiosis. Thus, our definitive knowledge of the oral commensal bacteria and oral cancer link can definitely be used as a potential adjunct to early diagnosis and management of PMDs and prevent it’s malignant transformation. Study Design: A total of 100 individuals of minimum 18 years of age were included in the study which, were classified into 2 groups of tobacco users (50) and non-tobacco users (50). The tobacco users had a history of tobacco consumption for at least 5 years. Results: The present study, showed highest percentage (72%) of anaerobic bacteria, followed by aerobic (22%) and lowest count of yeast (4%). Conclusion: The ecological shift to dysbiosis is a significant finding in oral carcinogenesis. Further investigation on a larger group of altered microbiomes will definitely help in establishing relationship of altered microbiome and PMDs, which can help in appropriate treatment and better prognosis.     

Implication of ERBB2 as a Predictive Tool for Survival in Patients with Pancreatic Cancer in Histological Studies

Pancreatic cancer will be positioned by the year 2030 as the second cause of oncological death after lung cancer. The pathophysiology of the most common variety, which involves the adenocarcinoma of the pancreas, represents one of the main challenges for current oncology to explain its tumorigenesis and create a targeted treatment. The tumor microenvironment, metastatic capacity, and lack of early diagnosis lead patients to present advanced stages at the time of diagnosis. Despite numerous efforts, little progress has been made in clinical outcomes and with respect to the improved survival of these patients. For this reason, in recent years, numerous diagnostic tests, treatments, and possible approaches in the fields of radiotherapy, chemotherapy, immunotherapy, and surgery have been developed to find a combination of methods that improves life expectancy in patients diagnosed with this disease. On the other hand, the scientific community has made numerous advances in the molecular bases of pancreatic cancer since several oncogenetic pathways have been described and the markers expressed by the tumor have proven to be useful in the prognosis of pancreatic adenocarcinoma. These molecular alterations allow the study of possible therapeutic targets that improve the prognosis of these patients, but even numerous tumor cell-individual interactions must be explained to understand the underlying pathophysiology causing the high mortality. Therefore, the purpose of our study is to examine the expression of markers such as EGFR, Cyclin D1, andCDK4 in order to find a relationship with the possible long-term prognostic factors of patients affected by pancreatic ductal adenocarcinoma. Our results show that there is a prognostic role for ErbB2, EGFR, beta catenin, cyclin D1, and CDK4. Of these, we highlight the clinical importance of ErbB2 in the survival rates of patients who overexpress this component.     

Parent’s Perspective on Teletherapy of Pediatric Population with Speech and Language Disorder During Covid-19 Lockdown in India

Aim: The pandemic COVID-19 led to the sudden imposition of lockdown and travel restrictions worldwide, that made tele practice one of the most viable options for various hospitals and healthcare centres. The present study aimed at exploring the parental perspective on teletherapy, for children having speech and language delay, during the covid-19 pandemic lockdown. Material & method: A total of 100 parents with children with speech and language delays and who have undergone a minimum of five teletherapy sessions at a tertiary care hospital during the COVID-19 pandemic lockdown were recruited. A questionnaire with 12 close-ended questions was administered over the phone call to know the parent’s perspective on the impact of teletherapy and its benefits. The responses obtained were tabulated and calculated for percentage response to each question. Result: Around 95% of parents reported improved motivation for speech-language therapy for their child due to teletherapy during the COVID-19 pandemic lockdown, and 96% of parents were satisfied with receiving teletherapy services during the COVID-19 pandemic lockdown. Furthermore, 90% of parents found teletherapy is more cost-effective than in-person therapy, but 88% believe face-to-face consultation is also required after some time (approx. after six months). Conclusion: The overall result suggested that parents had a positive attitude towards the teletherapy sessions. They reported the therapy sessions to be very effective and compliant, and it can be an efficient alternative with more structured implementation.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12070-022-03310-y.     

Immunohistochemistry-Based Consensus Molecular Subtypes as a Prognostic and Predictive Biomarker for Adjuvant Chemotherapy in Patients with Stage II Colorectal Cancer

BackgroundFor stage II colorectal cancer (CRC), the efficacy of adjuvant chemotherapy remains controversial. Consensus molecular subtype (CMS) has been validated to be a prognostic tool for CRCs. In this study, CMS status was investigated as a prognostic biomarker for the efficacy of adjuvant chemotherapy for stage II colorectal cancer.Materials and MethodsThe tissue microarray was retrospectively constructed of 165 nonconsecutive, primary, and sporadic stage II CRCs. CMS status was determined by immunohistochemistry staining of CDX2, HTR2B, FRMD6, and ZEB1, combining with microsatellite instability testing. The prognostic for adjuvant chemotherapy efficacy of CMS status was calculated by Kaplan‐Meier curves and Cox regression analysis. Subgroup analyses were conducted according to tumor location.ResultsKaplan‐Meier curves indicated that CMS was associated with overall survival (OS) and disease‐free survival for stage II CRCs. Cox regression analysis showed that CMS was an independent risk factor for OS. Among high‐risk clinicopathological factors, patients with CMS2/3 (hazard ratio [HR]: 0.445, 95% confidence interval [CI]: 0.227–0.875), left‐sided tumors (HR: 0.488, 95% CI: 0.247–0.968), or fewer than 12 lymph nodes examined (HR: 0.307, 95% CI: 0.097–0.974) had survival benefit from adjuvant chemotherapy. Subgroup analysis showed that adjuvant chemotherapy only improved OS for patients with left‐sided tumors of CMS2/3 subtype. Regardless of CMS, right‐sided tumors had no benefit from adjuvant chemotherapy.ConclusionCMS is a better prognostic factor for adjuvant chemotherapy for stage II CRCs. Together with tumor location, CMS classification will aid in personalized treatment for stage II CRCs.Implications for PracticeFor stage II colorectal cancer (CRC), the efficacy of adjuvant chemotherapy remains controversial, in that its minimal benefit (no more than 5% on average) is considered not worth the toxic effects of the drugs. There are still no effective prognostic and predictive biomarkers. This study showed that consensus molecular subtype (CMS) status is a predictive marker for adjuvant chemotherapy efficacy. Patients with left‐sided tumors of CMS2/3 subtype have survival benefit by receiving adjuvant chemotherapy, which will aid in personalized treatment for stage II CRCs. Moreover, this test of CMS based on immunohistochemistry is cheap, not time consuming, and easily conducted in the laboratories of most hospitals.     

DNA Repair Gene Patterns as Prognostic and Predictive Factors in Molecular Breast Cancer Subtypes

DNA repair pathways can enable tumor cells to survive DNA damage induced by chemotherapy and thus provide prognostic and/or predictive value. We evaluated Affymetrix gene expression profiles for 145 DNA repair genes in untreated breast cancer (BC) patients (n = 684) and BC patients treated with regimens containing neoadjuvant taxane/anthracycline (n = 294) or anthracycline (n = 210). We independently assessed estrogen receptor (ER)‐positive/HER2‐negative, HER2‐positive, and ER‐negative/HER2‐negative subgroups for differential expression, bimodal distribution, and the prognostic and predictive value of DNA repair gene expression. Twenty‐two genes were consistently overexpressed in ER‐negative tumors, and five genes were overexpressed in ER‐positive tumors, but no differences in expression were associated with HER2 status. In ER‐positive/HER2‐negative tumors, the expression of nine genes (BUB1, FANCI, MNAT1, PARP2, PCNA, POLQ, RPA3, TOP2A, and UBE2V2) was associated with poor prognosis, and the expression of one gene (ATM) was associated with good prognosis. Furthermore, the prognostic value of specific genes did not correlate with proliferation. A few genes were associated with chemotherapy response in BC subtypes and treatment‐specific manner. In ER‐negative/HER2‐negative tumors, the MSH2, MSH6, and FAN1 (previously MTMR15) genes were associated with pathological complete response and residual invasive cancer in taxane/anthracycline‐treated patients. Conversely, PMS2 expression was associated with residual invasive cancer in treatments using anthracycline as a single agent. In HER2‐positive tumors, TOP2A was associated with patient response to anthracyclines but not to taxane/anthracycline regimens. In genes expressed in a bimodal fashion, RECQL4 was significantly associated with clinical outcome. In vitro studies showed that defects in RECQL4 impair homologous recombination, sensitizing BC cells to DNA‐damaging agents.     

Progress in the Development of Prognostic and Predictive Markers for Gastrointestinal Malignancies

Opinion statement Gastrointestinal cancers remain a significant cause of morbidity and mortality. While increasing therapeutic options have improved outcomes for many patients, they have also complicated treatment decision-making. Unfortunately, most patients with advanced gastrointestinal malignancies die from their disease. Prognostic and predictive markers could improve treatment significantly by identifying patients who may or may not require a given therapy, and determining those most likely to benefit from a therapy. Candidates for such markers include blood antigens and circulating tumor cells, tumor enzyme and gene expression, and pharmacodynamic endpoints. In this review, we summarize reported and ongoing research to define and validate prognostic and predictive markers in gastrointestinal malignancies, with an emphasis on colorectal cancer and brief overview of pancreatic and neuroendocrine tumors.     

Evolution of a Systematic Approach to Smoking Cessation in Ontario’s Regional Cancer Centres

Smoking cessation after a cancer diagnosis can significantly improve a person’s prognosis, treatment efficacy and safety, and quality of life. In 2012, Cancer Care Ontario (now part of Ontario Health) introduced a Framework for Smoking Cessation, to be implemented for new ambulatory cancer patients at the province’s 14 Regional Cancer Centres (RCCs). Over time, the program has evolved to become more efficient, use data for robust performance management, and broaden its focus to include new patient populations and additional data collection. In 2017, the framework was revised from a 5As to a 3As brief intervention model, along with an opt-out approach to referrals. The revised model was based on emerging evidence, feedback from stakeholders, and an interim program evaluation. Results showed an initial increase in referrals to cessation services. Two indicators (tobacco use screening and acceptance of a referral) are routinely monitored as part of Ontario Health’s system-wide performance management approach, which has been identified as a key driver of change among RCCs. Due to the COVID-19 pandemic, many RCCs reported a decrease in these indicators. RCCs that were able to maintain a high level of smoking cessation activities during the pandemic offer valuable lessons, including the opportunity to swiftly leverage virtual care. Future directions for the program include capturing data on cessation outcomes and expanding the intervention to new populations. A focus on system recovery from COVID-19 will be paramount. Smoking cessation must remain a core element of high-quality cancer care, so that patients achieve the best possible health benefits from their treatments.     

Evaluation of Prognostic and Predictive Models in the Oncology Clinic

Predictive and prognostic models hold great potential to support clinical decision making in oncology and could ultimately facilitate a paradigm shift to a more personalised form of treatment. While a large number of models relevant to the field of oncology have been developed, few have been translated into clinical use and assessment of clinical utility is not currently considered a routine part of model development. In this narrative review of the clinical evaluation of prediction models in oncology, we propose a high-level process diagram for the life cycle of a clinical model, encompassing model commissioning, clinical implementation and ongoing quality assurance, which aims to bridge the gap between model development and clinical implementation.     

Prognostic and Predictive Value of Tumor Budding in Colorectal Cancer

BackgroundTumor budding (TB) is an adverse prognostic factor in colorectal cancer (CRC). International consensus on a standardized assessment method has led to its wider reporting. However, uncertainty regarding its clinical value persists. This study aimed to (1) confirm the prognostic significance of TB, particularly in stage II CRC; (2) to determine optimum thresholds for TB risk grouping; and (3) to determine whether TB influences responsiveness to chemotherapy.MethodsTB was assessed in CRC sections from 1575 QUASAR trial patients randomized between adjuvant chemotherapy and observation. Optimal risk group cutoffs were determined by maximum likelihood methods, with their influence on recurrence and mortality investigated in stratified log-rank analyses on exploratory (n = 504), hypothesis-testing (n = 478), and final (n = 593) data sets.ResultsThe optimal threshold for high-grade TB (HGTB) was ≥ 10 buds per 1.23 mm². High-grade TB tumors had significantly worse outcomes than those with lower TB: 10-year recurrence 36% versus 22% (risk ratio, 2.00 [95% CI, 1.62-2.45]; 2P < .0001) and 10-year mortality 50% vs. 37% (risk ratio, 1.53 [95% CI, 1.34-1.76]; 2P < .0001). The prognostic significance remained equally strong after allowance for other pathological risk factors, including stage, grade, lymphovascular invasion, and mismatch repair status. There was a nonsignificant trend toward increasing chemotherapy efficacy with increasing bud counts.ConclusionsTB is a strong independent predictor of recurrence. Chemotherapy efficacy is comparable in patients with higher and lower TB; hence, absolute reductions in recurrence and death with chemotherapy should be about twice as large in patients with ≥ 10 than < 10 TB counts.     

Prognostic and Predictive Value of Tumor-Infiltrating Lymphocytes in Breast Cancer

Recent attention has focused on the antitumor immune response in breast cancer, in particular, the role of tumor-infiltrating lymphocytes (TILs). In certain breast cancer subtypes, the presence of TILs has prognostic value and is associated with clinical outcome and improved survival. The potential predictive value of TILs has also been investigated in regard to cytotoxic and antihuman epidermal growth factor receptor 2 (HER-2) therapies, but could also serve as a selection marker for novel immunotherapies. In this article, we review the current literature on TILs in breast cancer and discuss how TILs are emerging as a promising biomarker in mediating antitumor immunity.     

Prognostic Association of C-Erbb-2 Oncogene Amplification and Protein Overexpression in Human Breast Cancer Using Archival Tissues a Comparative Study

The prognostic associations of c-erbB-2 gene amplification analysed by dot-blot hybridization and of c-erbB-2 protein overexpression assessed by immunohistochemistry (IHC) were compared in 161 patients with operable breast cancer using formalin fixed paraffin embedded archival tissues. The efficiency of the dot-blot technique to detect c-erbB-2 amplification was first validated by comparing the results of dot-blot with those of Southern blot hybridization in 134 tumour samples and there was an excellent correlation. In the main series of 161 samples, where results of IHC and dot-blot were compared, 35.4% showed c-erbB-2 overexpression and 17.4% showed gene amplification. Tumours showing overexpression of c-erbB-2 protein had a significantly shorter disease-free survival (DSF) and survival(s) compared to tumours showing no overexpression. A multivariate analysis revealed that c-erbB-2 overexpression was independently correlated with poor prognosis. On the other hand, no significant association between c-erbB-2 gene amplification and DFS or S was observed. We conclude that c-erbB-2 protein overexpression assessed by IHC is a superior prognostic indicator in operable breast cancer compared to c-erbB-2 gene amplification analysed by the dot-blot technique.