The Prediction of Metastases of Lateral Cervical Lymph Node in Medullary Thyroid Carcinoma.

Purpose: Development and validation of a nomogram for the prediction of lateral lymph node metastasis (LLNM) in medullary thyroid carcinoma (MTC). Methods: We retrospectively reviewed the clinical features of patients with MTC in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2017 and in our Department of Surgical Oncology, Hangzhou First People's Hospital between 2009 and 2019. The log-rank test was used to compare the difference in the Kaplan-Meier (K-M) curves in recurrence and survival. The nomogram was developed to predict the risk of LLNM in MTC patients. The prediction efficiency of the predictive model was assessed by area under the curve (AUC) and concordance index (C-index) and calibration curves. Decision curve analysis (DCA) was performed to determine the clinic value of the predictive model. Result: A total of 714 patients in the SEER database and 35 patients in our department were enrolled in our study. Patients with LLNM had worse recurrence rate and cancer-specific survival (CSS) compared with patients without LLNM. Five clinical characteristics including sex, tumor size, multifocality, extrathyroidal extension, and distant metastasis were identified to be associated with LLNM in MTC patients, which were used to develop a nomogram. Our prediction model had satisfied discrimination with a C-index of 0.825, supported by both training set and internal testing set with a C-index of 0.825, and 0.816, respectively. DCA was further made to evaluate the clinical utility of this nomogram for predicting LLNM. Conclusions: Male sex, tumor size >38mm, multifocality, extrathyroidal extension, and distant metastasis in MTC patients were significant risk factors for predicting LLNM.

Extranodal Extension Is an Independent Prognostic Factor in Papillary Thyroid Cancer: A Propensity Score Matching Analysis.

Purpose: To investigate the prognostic significance of extranodal extension (ENE) in papillary thyroid cancer (PTC). Methods: Seven hundred forty-three PTC patients were enrolled in the study from January 2014 to December 2017. The patients were dichotomized according to the presence of ENE. Logistic analysis was used to compare differences between the two groups. Kaplan-Meier (K-M) curve and propensity score matching (PSM) analyses were used for recurrence-free survival (RFS) comparisons. Cox regression was performed to analyze the effects of ENE on RFS in PTC. Results: Thirty-four patients (4.58%) had ENE. Univariate analysis showed that age, tumor size, extrathyroidal extension, and nodal stage were associated with ENE. Further logistic regression analysis showed that age, extrathyroidal extension, and nodal stage remained statistically significant. Evaluation of K-M curves showed a statistically significant difference between the two groups before and after PSM. Cox regression showed that tumor size and ENE were independent risk factors for RFS. Conclusions: Age ≥55 years, extrathyroidal extension, and lateral cervical lymph node metastasis were identified as independent risk factors for ENE. ENE is an independent prognostic factor in PTC.

Low prevalence of mismatch repair deficiency in Chinese colorectal cancers: a multicenter study.

BACKGROUND: Although universal testing for mismatch repair deficiency (dMMR) has been recommended to all colorectal cancer (CRC) patients, related evidence for the Chinese population is lacking. Here, we investigated the prevalence and clinicopathological features of dMMR patients in a large Chinese CRC cohort. METHODS: We included 7,373 CRC patients treated at four Chinese medical centers between August 2010 and September 2016. Patients' baseline characteristics and pathological features were recorded. The clinicopathological features were compared between patients with MLH1/PMS2 deficiency (dMLH1/PMS2) and MSH2/MSH6 deficiency (dMSH2/MSH6). RESULTS: Among the investigated patients, 654 (8.9%) were identified with dMMR CRCs and, of them, 401 (61.3%) were males, with a median age of 55 years (range, 22-87 years); 355 (54.3%) had stage II CRC based on American Joint Committee on Cancer 8th edition. The prevalence of the dMLH1/PMS2 group and the dMSH2/MSH6 group were 51.5% (337/654) and 25.1% (164/654), respectively. Compared with dMSH2/MSH6 patients, those with dMLH1/PMS2 were older (57 vs 52 years, P < 0.001), more likely to be female (45.7% vs 31.5%, P = 0.004), prone to having tumors located in the right-hand side of the colon (59.0% vs 47.6%, P = 0.015), and less likely to have a family history of tumors (29.7% vs 43.3%, P = 0.003). CONCLUSIONS: The prevalence of dMMR in Chinese CRC patients was low, especially in the dMLH1/PMS2 group. The clinicopathological features were different between dMMR subgroups.

Overexpression of p42.3 promotes cell proliferation, migration, and invasion in human gastric cancer cells.

As a newly discovered tumor-specific gene, p42.3 is overexpressed in most of human gastric cancers (GC). However, the role of p42.3 in GC progression remains unclear. To assess the role of p42.3 in gastric cancers, immunohistochemistry and western blot were performed to detect the p42.3 expression in human GC tissues and cells. We also investigated the role of p42.3 in GC cell proliferation, migration, and invasion. Our results showed that the p42.3 expression was increased dramatically in human GC tissue and cells. In addition, we found that overexpression of p42.3 promotes GC cell proliferation, migration, and invasion abilities. Furthermore, p42.3 expression suppressed the E-cadherin protein level and promoted the ß-catenin and p-ERK protein level. Taken together, overexpressed p42.3 is correlated with gastric cancer cell proliferation, migration, and invasion, suggesting its use as a biological marker in gastric cancer.

p21-Activated kinase 5 affects cisplatin-induced apoptosis and proliferation in hepatocellular carcinoma cells.

p21-Activated kinase 5 (PAK5) is the last identified member of the PAK family. The PAKs are highly conserved serine/threonine and effector proteins for Cdc42 and Rac and are essential in regulating cell motility and survival. Previous studies have demonstrated that PAK5 played a pivotal role in apoptosis, proliferation, cancer migration, and invasion. However, the biological function of PAK5 in hepatocellular carcinoma, as well as its underlying mechanism, still remains to be fully elucidated. In the present study, we demonstrated that PAK5 markedly inhibited cisplatin-induced apoptosis and promoted cell proliferation in hepatocellular carcinoma cells. Moreover, our results showed that overexpression of PAK5 contributed to cell cycle regulation. In order to elucidate the underlying mechanism of PAK5 on cisplatin-induced apoptosis and cell cycle regulation, we also examined the protein expressions of chk2 and p-chk2. In summary, our study investigated the role of PAK5 in cisplatin-induced cellular processes and provided evidence of its underlying mechanism.

p42.3: An abductor of cell cycle.

As a newly discovered tumor-associated gene, p42.3 was originally ascertained in gastric cancer cell line BGC823 and has been confirmed as a cell cycle-dependent gene that is overexpressed in many human tumor cell lines and embryonic tissues. p42.3 can regulate the level of relevant cycle-dependent proteins and promote malignant transformation of cells. A variety of cellular functions, including cell proliferation, cell invasion and cell migration, are under control of p42.3. Our review, namely the introduction of the structure of p42.3, underlying activity regulation mechanisms of p42.3 as well as the role p42.3 plays in malignant cellular transformation process, are accompanied by the presentation of potential directions of further researches of cancer prevention and therapy in which p42.3 is inevitable.

p42.3 promotes cell proliferation and invasion in human Renal-Cell Carcinoma.

p42.3 is a tumor-specific gene and found to be over-expressed in many tumor cell lines and primary tumor tissues. It plays a significant role in neoplastic transformation and tumor progression. To date, the association between p42.3 and Renal-Cell Carcinoma (RCC) has not been reported. This study investigated the biological effects and mechanisms of p42.3 in RCC progression. In this study, we found that p42.3 is overexpressed in various kinds of RCC cells, and knockdown of p42.3 dramatically reduced cell proliferation and invasion in vitro. Our studies revealed that overexpression of p42.3 accelerates the epithelial-mesenchymal transition (EMT) progression and induces RCC cells proliferation and invasion. Further studies show that p42.3 may involve in activation of ß-catenin and participate in RCC cell invasion. Combined, these data indicate that p42.3 contributes to promoting RCC cells proliferation and invasion through accelerates the EMT progression and ß-catenin activation.

Overexpression of p42.3 promotes cell growth and tumorigenicity in hepatocellular carcinoma.

AIM: To investigate the association of p42.3 expression with clinicopathological characteristics and the biological function of p42.3 in human hepatocellular carcinoma (HCC). METHODS: We used reverse transcription-polymerase chain reaction (RT-PCR), quantitative real-time RT-PCR and western blotting to detect p42.3 mRNA and protein expression in hepatic cell lines. We examined primary HCC samples and matched adjacent normal tissue by immunohistochemistry to investigate the correlation between p42.3 expression and clinicopathological features. HepG2 cells were transfected with a pIRES2-EGFP-p42.3 expression vector to examine the function of the p42.3 gene. Transfected cells were analyzed for their viability and malignant transformation abilities by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay, and tumorigenicity assay in nude mice. RESULTS: p42.3 is differentially expressed in primary HCC tumors and cell lines. Approximately 69.6% (96/138) of cells were p42.3-positive in hepatic tumor tissues, while 30.7% (35/114) were p42.3-positive in tumor-adjacent normal tissues. Clinicopathological characteristics of the HCC specimens revealed a significant correlation between p42.3 expression and tumor differentiation (P = 0.031). However, p42.3 positivity was not related to tumor tumor-node-metastasis classification, hepatitis B virus status, or hepatoma type. Regarding p42.3 overexpression in stably transfected HepG2 cells, we discovered significant enhancement of cancer cell growth and colony formation in vitro, and significantly enhanced tumorigenicity in nude mice. Western blot analysis of cell cycle proteins revealed that enhanced p42.3 levels promote upregulation of proliferating cell nuclear antigen, cyclin B1 and mitotic arrest deficient 2. CONCLUSION: p42.3 promotes tumorigenicity and tumor growth in HCC and may be a potential target for future clinical cancer therapeutics.

p42.3: a promising biomarker for the progression and prognosis of human colorectal cancer.

PURPOSE: As a novel cell cycle-related gene, p42.3 has been shown to play a key role in the cell proliferation and tumorigenicity of gastric cancer. To date, the association between p42.3 and colorectal cancer (CRC) has not been reported. This study investigated the expression of p42.3 and its potential role in human colorectal cancers. METHODS: Real-time polymerase chain reaction and western blotting were used to evaluate p42.3 mRNA and protein expression in 14 pairs of fresh frozen CRC samples, matched with adjacent normal mucosa. The p42.3 protein was evaluated by immunohistochemistry using CRC tissue microarrays, which included 212 CRC specimens and corresponding normal colorectal mucosa. The expression profiles of p42.3 in CRC tissues were analyzed against clinicopathological factors and post-surgical survival status. The expression profiles of p42.3 were also investigated in six human colon carcinoma cell lines. RESULTS: p42.3 was demonstrated to be over-expressed in colorectal cancer tissues compared with normal mucosa in the 14 tissue pairs (P = 0.011) and was significantly higher in patients with poor tumor differentiation (P = 0.045); patients positive for p42.3 expression had a poorer prognosis than those not expressing this protein (P = 0.033). In a multivariate survival analysis, p42.3 expression was identified as an independent prognostic factor for CRC patients (P = 0.030). CONCLUSIONS: The results indicated that p42.3 might play an important role in the progression of CRC, and it has a great value for assessing CRC patient prognosis after surgery.