Development and Validation of a Robust Apoptosis-related Prognostic Classifier in Patients With Osteosarcoma

Background: Apoptosis plays an important role in the tumorigenesis and the development of osteosarcoma, but the reliable biomarkers for individual treatment and prognosis of osteosarcoma based on apoptosis is lacking.Methods: A total of 1476 apoptosis-related genes were extracted from pathways and biological processes associated with apoptosis downloaded from MSigDB. All of those genes were used to identified the prognosis-related genes by univariate cox regression in the TARGET dataset and the ARS was constructed using the LASSO regression. The performance of the classifier was verified in the training and validation groups. The infiltration of immune cells and the expression levels of the immune checkpoint in different groups were also analyzed. Finally, a nomogram based on ARS and other Clinicopathological factors was constructed to facilitate clinical application.Results: ARS containing 22 apoptosis-related genes were identified, and its predictive ability performed well in both the training and validation groups. Macrophages M1 were highly expressed in the low-score group, and NK cells resting was highly expressed in the high-score group. The samples with low-score had higher expression of CTLA4 and PDL1. A nomogram with excellent predictive effectiveness (AUC= 0.932, 0.984, 0.939, 0.939, 0.948) was constructed to facilitate clinical decision-making.Conclusion: A prognostic classifier based on 22 apoptosis-related genes and a nomogram were constructed to predict the overall survival of patients with osteosarcoma. The classifier also provides a reference for selecting suitable patients for immunotherapy and targeted therapy.

Infleunce of Body Mass Index (BMI) on Outcome of Colon Cancer in Relationships with Other Clinicopathological Factors

Background: Colon cancer is the third most common cancer. High (BMI) contributes hazardously for several types of malignancies including colon cancer while the effect of BMI as a prognostic factor is poorly defined. Objective: Demonstrating the influence of increasing (BMI) on colon cancer recurrence. Patients and Methods: Case-control study involved a sample of 312 patients and 131 patients were excluded from this study and only 181 patients of colon cancer are included in the study with stage 2 and 3 who did underwent a surgical operation and received adjuvant chemotherapy recruited from an oncology teaching hospital, Al Jawad oncology center (Alkadhemiya hospital) and Babylon Oncology center. Results: The study involved 181 patients of colon cancer patients with mean age of 56.25 ±11.74years the highest proportion of study patients (90.6%) were aged more than 40yrs with a male to female ratio (1.2:1). Overweight patients constituted 39.2% and obese 23.8% and normal body weight 37%. In this study majority of tumors are ulcerating for about 72.5% and sigmoid and left side colon was the most common site of the tumor in about 53% with stage three is a most common type. Regarding recurrence, 54.1% of study patients have recurrence, and the majority of the 41.8% occurs between 1-3years after primary tumors diagnoses and treatment with a high prevalence of recurrence was seen in obese patients (74.4%) with a significant association between prevalence of recurrence and increasing BMI. In this study, 61.2% of patients with lymphovascular invasion have recurrences of malignancy with significant associations between recurrences and LVIe. Also more than 50% of patient older than 40years got recurrences with significant associations between recurrences with age of patients. In this study we take the effect of each clinicopathological feature on the outcome of colon cancer and then to excluded its effect by logistic regression to see the effect of only BMI on the outcome of colon cancer. Conclusion: Increase body mass index is associated with increase recurrence of colon cancer Keywords: Colon cancer recurrence, body mass index, Clinicopathological Factors

Does failed mapping predict sentinel lymph node metastasis in cN0 breast cancer?

Aims: The clinical significance of nonvisualized sentinel lymph nodes (non-vSLNs) is unknown. The authors sought to determine the incidence of non-vSLNs on lymphoscintigraphy, the identification rate during surgery, factors associated with non-vSLNs and related axillary management. Patients & methods: A total of 30,508 consecutive SLN procedures performed at a single institution from 2000 to 2017 were retrospectively studied. Associations between clinicopathological factors and the identification of SLNs during surgery were assessed. Results: Non-vSLN occurred in 525 of the procedures (1.7%). In 73.3%, at least one SLN was identified intraoperatively. Nodal involvement was only significantly associated with SLN nonidentification (p < 0.001). Conclusion: Patients with non-vSLN had an increased risk for SLN metastasis. The detection rate during surgery was consistent, reducing the amount of unnecessary axillary dissection.

A nomogram for predicting probability of low risk of MammaPrint results in women with clinically high-risk breast cancer

We aimed to develop a prediction MammaPrint (MMP) genomic risk assessment nomogram model for hormone-receptor positive (HR+) and human epidermal growth factor receptor-2 negative (HER2–) breast cancer and minimal axillary burden (N0-1) tumors using clinicopathological factors of patients who underwent an MMP test for decision making regarding adjuvant chemotherapy. A total of 409 T1-3 N0-1 M0 HR + and HER2– breast cancer patients whose MMP genomic risk results and clinicopathological factors were available from 2017 to 2020 were analyzed. With randomly selected 306 patients, we developed a nomogram for predicting a low-risk subgroup of MMP results and externally validated with remaining patients (n = 103). Multivariate analysis revealed that the age at diagnosis, progesterone receptor (PR) score, nuclear grade, and Ki-67 were significantly associated with MMP risk results. We developed an MMP low-risk predictive nomogram. With a cut off value at 5% and 95% probability of low-risk MMP, the nomogram accurately predicted the results with 100% positive predictive value (PPV) and negative predictive value respectively. When applied to cut-off value at 35%, the specificity and PPV was 95% and 86% respectively. The area under the receiver operating characteristic curve was 0.82 (95% confidence interval [CI] 0.77 to 0.87). When applied to the validation group, the nomogram was accurate with an area under the curve of 0.77 (95% CI 0.68 to 0.86). Our nomogram, which incorporates four traditional prognostic factors, i.e., age, PR, nuclear grade, and Ki-67, could predict the probability of obtaining a low MMP risk in a cohort of high clinical risk patients. This nomogram can aid the prompt selection of patients who does not need additional MMP testing.

A Study on the Clinicopathological Characteristics Associated with Cervical Lymph Mode Metastasis and Extra-nodal Extension in Patients with Oral Cancer

Background/Objectives: Extra-nodal extension (ENE) is one of the strongest prognosticators in oral cancers. Here we tried to evaluate clinicopathological factors associated with the presence of ENE.Materials & Methods: We retrospectively analyzed clinical information of 120 patients who diagnosed with oral cancer and received curative surgery at our hospital from Mar 2012 to Apr 2020. We comparatively analyzed clinicopathological factors associated with the presence of lymph node (LN) metastasis and ENE, respectively.Results: Variable factors of primary tumor characteristics such as lymphovascular invasion, perineural invasion, largest diameter of tumor, depth of invasion and maximum standardized uptake value were significantly associated with the presence of cervical LN metastasis. The largest diameter of tumor was statistically significant also in multivariate analysis for predicting the LN metastasis. Meanwhile, the association between primary tumor characteristics and the presence of ENE were not statistically significant except the primary tumor size. Importantly, factors associated with LN characteristics including the maximum diameter and number of metastatic LNs were significantly associated with ENE.Conclusion: In this study, several factors affecting cervical LN metastasis and ENE in oral cancer patients were identified. The ENE seems to be influenced by the status of the metastatic LNs, such as the number of metastatic LNs, rather than the characteristics of the primary tumor itself.

Nomogram to Predict Tumor-Infiltrating Lymphocytes in Breast Cancer Patients

Background: Tumor-infiltrating lymphocytes (TILs) play important roles in the prediction of prognosis and neoadjuvant therapy (NAT) efficacy in breast cancer (BRCA) patients, in this study, we identified clinicopathological factors related to BRCA TILs, then to construct and validate nomogram to predict high density of TILs.Methods: A total of 826 patients diagnosed with BRCA in Sun Yat-Sen University cancer center were enrolled in nomogram cohort. TILs were assessed using hematoxylin-eosin (H&amp;E) staining by two pathologists. Complete clinical data were collected for analysis. Then the enrolled patients were split into a training set and validation set at a ratio of 8:2. and the backward multivariate binary logistic regression model was used to establish nomogram for predicting BRCA TILs, which were further evaluated and validated using the C-index, receiver operating characteristic (ROC) curves and calibration curves. Then another independent NAT cohort of 106 patients was established for verifying this nomogram in NAT efficacy prediction.Results: TILs were significantly correlated with body mass index (BMI), tumor differentiation, ER, PR, HER2 expression, Ki67, blood biochemical indicators including total bilirubin (TBIL), indirect bilirubin (IBIL), total protein (TP), Globulin (GLOB), inorganic phosphorus (IP), calcium (Ca). In which ER expression level [OR = 0.987, 95%CI (0.982–0.992), p &lt; 0.001], IP [OR = 4.462, 95%CI (1.171∼17.289), p = 0.029], IBIL [OR = 0.906, 95%CI (0.845–0.966), p = 0.004] and TP [OR = 1.053, 95%CI (1.010–1.098, p = 0.016)] were independent predictors of TILs. Then nomogram was established, for which calibration curves (C-index = 0.759) and ROC curve (AUC = 0.759, 95%CI 0.717–0.801) in training sets, calibration curves (C-index = 0.708) and ROC curve (AUC = 0.708, 95%CI 0.617–0.800) in validation sets demonstrated great evaluation efficiency. Besides, independent NAT cohort verified this nomogram can distinguish patients with greater NAT efficacy (p = 0.041).Conclusion: The finds of clinicopathological factors associated with TILs could help clinicians to understand the tumor immunity of BRCA and improve treatment system for patients, and the established nomogram with high evaluation efficiency may be used as a complement tool for distinguishing patients with better NAT efficacy.

Clinicopathological factors associated with recurrence in patients undergoing resection of pancreatic solid pseudopapillary neoplasm

Purpose Solid pseudopapillary neoplasm (SPN) is an uncommon pathology with a low-grade malignancy. Surgery is the milestone treatment. Nevertheless, despite appropriate management, some patients present recurrence. Risk factors associated with recurrence are unclear. The objective was to identify the clinicopathological factors associated with recurrence in patients with SPN treated with pancreatic resection. Methods Medical records of patients treated with pancreatic resection during 2006–2020 were evaluated. Patients with histological diagnosis of SPN were included. Survival analysis was performed to identify the clinicopathological factors related to recurrence. Results Seventy-four patients were diagnosed with SPN; 70 (94.6%) patients were female, and the median age was 20 years old. The median tumor diameter was 7.9 cm. Multivisceral resection was performed in 9 (12.2%) patients. Four (5.4%) patients presented lymph node metastasis.R0 resection was achieved in all cases. Six (8%) patients presented recurrence and the liver was the most frequent recurrence site (n = 5).After a median follow-up of 40.2 months, 9 (12%) patients died. Five (6.8%) patients died of disease progression. The 1–3- and 5-year overall survival (OS) was 97.1%, 90.2% and 79.9%, respectively. The 1–3-and-5-year recurrence-free survival (RFS) was 98.4%, 89.9% and 87%, respectively. In the univariate Cox-regression analysis, age ≥ 28 years(HR = 8.61, 95% CI 1.1–73.8),tumor diameter ≥ 10 cm(HR = 9.3, 95% CI 1.12–79.6),invasion of adjacent organs (HR = 7.45, 95% CI 1.5–36.9), lymph node metastasis (pN +) (HR = 16.8, 95% CI 2.96–94.9) and, AJCC Stage III (HR = 10.1, 95% CI 1.2–90.9) were identified as predictors for recurrence. Conclusions SPN is more frequently diagnosed in young women with a good overall prognosis after an R0 surgical resection even with disease recurrence. Age ≥ 28 years, larger tumors ≥ 10 cm, invasion of adjacent organs, lymph node metastasis(pN +) and, AJCC Stage III were predictors factors of recurrence in resected SPN.