Pan-cancer analysis of the oncogenic role of HNRNPR in human tumors.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are potential cancer biomarkers. Little is known about the role of HNRNPR, an essential member of the hnRNP family, in human tumours. This study aims to explore the potential value of HNRNPR across cancers, based on The Cancer Genome Atlas (TCGA). The expression level, mutation, DNA methylation, phosphorylation status, survival status, pathological stage, tumor mutation burden (TMB), microsatellite instability (MSI), immune cell infiltration, and immune signature related to HNRNPR were analyzed. HNRNPR expression level was increased in several types of cancer and was associated with poor prognosis, especially in liver hepatocellular carcinoma (LIHC). HNRNPR was also correlated with antitumour immunity, and associated with TMB, MSI, and immune cell activation status across cancers. Furthermore, nomograms were established to predict the prognosis of LIHC, based on HNRNPR and other clinical characteristics. Functional enrichment analysis showed the mechanisms of HNRNPR-mediated LIHC progression. Loss-of-function experiments demonstrated that inhibition of HNRNPR could remarkably suppress hepatocellular carcinoma (HCC) cell proliferation, migration, invasion, and Epithelial-Mesenchymal Transition abilities. Our study offers a comprehensive understanding of the oncogenic roles of HNRNPR across different tumours, and demonstrates that HNRNPR might foster the proliferation, migration, and invasion abilities of HCC cells.

Variability of radiotherapy volume delineation: PSMA PET/MRI and MRI based clinical target volume and lymph node target volume for high-risk prostate cancer.

PURPOSE: A comparative retrospective study to assess the impact of PSMA Ligand PET/MRI ([68 Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 PET/MRI) as a new method of target delineation compared to conventional imaging on whole-pelvis radiotherapy for high-risk prostate cancer (PCa). PATIENTS AND METHODS: Forty-nine patients with primary high-risk PCa completed the whole-pelvis radiotherapy plan based on PSMA PET/MRI and MRI. The primary endpoint compared the size and overlap of clinical target volume (CTV) and nodal gross tumour volume (GTVn) based on PSMA PET/MRI and MRI. The diagnostic performance of two methods for pelvic lymph node metastasis (PLNM) was evaluated. RESULTS: In the radiotherapy planning for high-risk PCa patients, there was a significant correlation between MRI-CTV and PET/MRI-CTV (P = 0.005), as well as between MRI-GTVn and PET/MRI-GTVn (P < 0.001). There are non-significant differences in the CTV and GTVn based on MRI and PET/MRI images (P = 0.660, P = 0.650, respectively). The conformity index (CI), lesion coverage factor (LCF) and Dice similarity coefficient (DSC) of CTVs were 0.999, 0.953 and 0.954. The CI, LCF and DSC of GTVns were 0.927, 0.284, and 0.32. Based on pathological lymph node analysis of 463 lymph nodes from 37 patients, the sensitivity, specificity of PET/MRI in the diagnosis of PLNM were 77.78% and 99.76%, respectively, which were higher than those of MRI (P = 0.011). Eight high-risk PCa patients who finished PSMA PET/MRI changed their N or M stage. CONCLUSION: The CTV delineated based on PET/MRI and MRI differ little. The GTVn delineated based on PET/MRI encompasses metastatic pelvic lymph nodes more accurately than MRI and avoids covering pelvic lymph nodes without metastasis. We emphasize the utility of PET/MRI fusion images in GTVn delineation in whole pelvic radiotherapy for PCa. The use of PSMA PET/MRI aids in the realization of more individual and precise radiotherapy for PCa.

Survival nomograms for colorectal carcinoma patients with lung metastasis and lung-only metastasis, based on the SEER database and a single-center external validation cohort.

BACKGROUND: We analysed the survival of colorectal cancer (CRC) patients with lung metastasis and lung-only metastasis and determined the risk factors for lung metastasis in CRC patients. METHODS: Data from colorectal cancer patients with lung metastasis diagnosed from 2010 to 2015 were obtained from the SEER database. Survival was analysed using the Kaplan-Meier method and log-rank test, the Cox proportional hazards regression model, and a competing risk model. The predictive ability of the nomgram was assessed by the concordance index (C-index) and calibration curves. The data from the SEER database for the period 2016-2019 was used as an external validation set. The characteristics of 70 CRC patients treated at Shanghai East Hospital between 2016 and 2019 were retrospectively analysed and data from China was chosen as an external validation set. RESULTS: The median survival time for colorectal cancer patients with lung metastasis was 12 months, while this value was 24 months in patients with lung-only metastasis. Among all CRC patients with lung metastasis, age, grade, T stage, N stage, presence of liver, brain or bone metastasis, anatomic site and surgery were related to overall survival (OS). In CRC patients with lung-only metastasis, age, T stage, marital status, chemotherapy and surgery were independent prognostic factors affecting OS. Two nomograms predicting OS were established, with great discrimination (C-index between 0.67 and 0.81) and excellent calibration. Factors including age, race, sex, tumour grade, T stage, N stage, presence of liver, brain or bone metastasis, marital status, insurance status and anatomic location were related to the occurrence of lung metastasis in CRC patients. CONCLUSION: We developed two reliable clinical prediction models among CRC patients to predict the OS rates in patients with lung metastasis and lung metastasis only.

A nomogram to predict the prognosis of patients with unresected rectal adenocarcinoma undergoing chemoradiotherapy: a population-based study.

Background: Chemotherapy combined with radiotherapy is the main treatment strategy for unresectable rectal cancer. However, the prognostic factors of patients with unresectable rectal cancer treated with radiotherapy and chemotherapy have not been systematically studied. Therefore, this study investigated the prognostic factors and prognosis based on surveillance, epidemiology and final results of the SEER medical insurance database. Methods: Primary rectum patients were selected from the SEER database. The independent prognostic factors associated with overall survival (OS), cancer-specific survival (CSS) and noncancer-related death were evaluated using the Kaplan-Meier method and log-rank test, a competing risk model, and the Cox proportional hazards regression model. Two nomograms were established for predicting the 1- and 3-year OS and CSS of patients. Results: A total of 3,998 rectal adenocarcinoma cancer patients who received chemoradiotherapy but had not undergone surgery were included in this study and divided into training (n = 3559) and validation cohorts (n = 439). Patients in the training cohort had a 1-year OS rate of 65.7±0.8%, a 3-year OS rate of 26.6±0.8%, a 5-year OS rate of 1.6±0.8%, and a median survival rate of 20.0 months (range, 19.22-20.8 months). The following factors were significant prognostic factors of OS: age (p< 0.001); tumour grade (p< 0.001); T stage (p< 0.001); M stage (p< 0.001); bone metastasis (p<0.001); brain metastases (p<0.001); liver metastases (p<0.001); lung metastases (p<0.001); marital status (p<0.001) and insurance status (p=0.005). Age (p< 0.001), tumour grade (p< 0.001), T stage (p< 0.001), M stage (p< 0.001), bone metastasis (p<0.001), brain metastases (p<0.001), liver metastases (p<0.001), lung metastases (p<0.001) and race (p=0.034) were independent prognostic factors of CSS. Age (p< 0.001), T stage (p< 0.001), N stage (p=0.007), M stage (p<0.001), liver metastases (p<0.001), lung metastases (p<0.001), marital status (p<0.001) and insurance status (p=0.019) were independently associated with noncancer-related death. Conclusion: Age, tumour grade, T and M stage, bone, brain, liver and lung metastases, marital status and insurance status are independent risk factors for the OS of rectal adenocarcinoma patients who have undergone chemoradiotherapy but have not undergone surgery. Age, tumour grade, T stage, M stage, bone, brain, liver, lung metastases and race were independent prognostic factors of CSS. Age, T, N and M stage, liver and lung metastases, marital status and insurance status, were independently associated with noncancer-related death. Interestingly, the earlier the T stage was, the higher the rate of noncancer-related death. Two nomograms were developed to predict OS and CSS, and the C-indexes were 0.6776 and 0.6744, respectively. Rectal cancer screening is strongly recommended for patients under the age of 50.