HER2 status is positively associated with vessel invasion of colorectal cancer: a retrospective large cohort study.

PURPOSE: HER2-positive colorectal cancer was drawn increasing attention in recent years. Accumulating evidence showed HER2-positive metastatic colorectal cancer could benefit from HER2-targeted therapy. While HER2 expression and the relationship between HER2 status and clinicopathological characteristics of overall colorectal cancer remains largely unknown. The aim of this study was to evaluate HER2 expression in colorectal cancer and compare the clinicopathological features between HER2-positive and HER2-negative colorectal cancer. METHODS: We retrospectively analyzed 3910 primary colorectal cancer patients treated in our institution from January 2016 to December 2019. Medical records and pathology reports after surgery were collected to provide information about HER2 status and other clinicopathological characteristics. RESULTS: We identified 3347 HER2-negative and 79 HER2-positive colorectal cancer patients in our cohort. The chi-square test showed that vessel invasion was significantly more common in HER2-positive colorectal cancer patients. Crude analysis showed HER2 positive was associated with vessel invasion in colorectal cancer [OR and 95% CI 0.534 (0.341, 0.835), p = 0.006]. After adjusting for N stage, a significant association was still observed between HER2 status and vessel invasion in colorectal cancer [OR and 95% CI 0.550 (0.322, 0.941), p = 0.029]. Survival analysis showed that there was no significant difference in 3-year overall survival rate between HER2 positive and HER2 negative group (p = 0.603). CONCLUSION: Our findings indicate that the rate of HER2 positivity in colorectal cancer was relatively low, and HER2 status was strongly associated with vessel invasion while having no significant influence on the 3-year overall survival rate in colorectal cancer patients.

CircCD44 plays oncogenic roles in triple-negative breast cancer by modulating the miR-502-5p/KRAS and IGF2BP2/Myc axes.

BACKGROUND: Emerging studies have revealed the potent functions of circRNAs in breast cancer tumorigenesis. However, the biogenesis, biofunction and mechanism of circRNAs in triple-negative breast cancer (TNBC) are largely unknown. METHODS: High-throughput RNA sequencing was applied to identify dysregulated circRNAs in TNBCs and paired normal tissues. RNA pulldown and luciferase assays were performed to investigate the interaction between circular CD44 (circCD44, also annotated as hsa_circ_0021735) and miR-502-5p. RNA pulldown and RIP assays were used to investigate the interaction between circCD44 and IGF2BP2. Cell viability, colony formation, migration/invasion assays and in vivo tumorigenesis were used to investigate circCD44 biological functions. RESULTS: CircCD44 is an uncharacterized circRNA, which is highly expressed in TNBC, and its expression is negatively correlated with the prognosis of TNBC patients. CircCD44 promotes TNBC proliferation, migration, invasion and tumorigenesis at least partially by sponging miR-502-5p and interacting with IGF2BP2. CONCLUSION: Our data suggested that overexpressed circCD44 promotes TNBC progression. CircCD44 is potentially a novel diagnostic and therapeutic marker for TNBC patients.

Apolipoprotein A1 is negatively associated with male papillary thyroid cancer patients: a cross-sectional study of single academic center in China.

BACKGROUND: Papillary thyroid cancer (PTC) is the most common type of thyroid cancer and the incidence of PTC has continued to increase over the past decades. Many studies have shown that obesity is an independent risk factor for PTC and obese PTC patients tend to have a relative larger tumor size and higher grade of tumor stage. Obesity is associated with disordered lipid metabolism and the relationship between serum lipids and PTC remains unclear. Therefore, this study aimed to investigate the association between serum lipid level and PTC. METHODS: We retrospectively analyzed 1018 PTC patients diagnosed and treated in our hospital, all these cases were first diagnosed with PTC and had complete clinical information including ultrasound reports before surgery, serum lipid (CHOL, TG, HDL-c, LDL-c, Apo-A1, Apo-B, Apo-E) results, surgical records and pathological reports. RESULTS: None of these lipid markers were associated with tumor size in the whole cohort and in the female group. In the male group, on crude analysis, Apo-A1 showed a marginally association with tumor size, [OR = 0.158 (0.021-1.777)], p = 0.072. After adjusting for age and multifocality, Apo-A1 showed a significant association with tumor size [OR = 0.126 (0.016-0.974)], p = 0.047. This association become more apparent in a young male subgroup, [OR = 0.051 (0.005-0.497)], p = 0.009. CHOL, TG, HDL-c, LDL-c, Apo-B, Apo-E did not show significant association with tumor size. As for LNM, neither in the male group nor in the female group were found to be associated with any serum lipid biomarkers. CONCLUSION: As PTC incidences continues to increase, our findings demonstrated a negatively association between PTC and apoA-1 in male PTC patients, which may contribute to further investigation concerning diagnosing and preventing this most common type of thyroid cancer.

Circular HER2 RNA positive triple negative breast cancer is sensitive to Pertuzumab.

BACKGROUND: Triple negative breast cancer (TNBC) remains the most challenging breast cancer subtype so far. Specific therapeutic approaches have rarely achieved clinical improvements in treatment of TNBC patients and effective molecular biomarkers are largely unknown. METHODS: We used paired TNBC samples and high throughput RNA sequencing to identify differentially expressed circRNAs. Sucrose gradient polysome fractionation assay, antibody and Mass spectra were used to validate active circRNA translation. The novel protein function was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by immunoprecipitation analyses and kinase activity assay. RESULTS: Circular HER2 RNA (circ-HER2) encoded a novel protein, HER2-103. Unexpectedly, while HER2 mRNA and protein were barely detected, circ-HER2/HER2-103 was expressed in ~ 30% TNBC clinical samples. Circ-HER2/HER2-103 positive TNBC patients harbored worse overall prognosis than circ-HER2/HER2-103 negative patients. Knockdown circ-HER2 inhibited TNBC cells proliferation, invasion and tumorigenesis in vitro and in vivo, suggesting the critical role of circ-HER2/HER2-103 in TNBC tumorigenicity. Mechanistically, HER2-103 promoted homo/hetero dimerization of epidermal growth factor receptor (EGFR)/HER3, sustained AKT phosphorylation and downstream malignant phenotypes. Furthermore, HER2-103 shared most of the same amino acid sequences as HER2 CR1 domain which could be antagonized by Pertuzumab, a clinical used HER2 antibody. Pertuzumab markedly attenuated in vivo tumorigenicity of circ-HER2/HER2-103 expressing TNBC cells but showed no effects in circ-HER2/HER2-103 negative TNBC cells. CONCLUSION: Our results not only demonstrated that certain TNBCs were not truly 'HER2 negative' but also highlighted the clinical implications of Pertuzumab in circ-HER2/HER2-103 expressing TNBC patients.

TSPAN1 inhibits metastasis of nasopharyngeal carcinoma via suppressing NF-kB signaling.

Nasopharyngeal carcinoma (NPC) originates in the epithelial cells of the nasopharynx and is a common malignant tumor in southern China and Southeast Asia. Metastasis of NPC remains the main cause of death for NPC patients even though the tumor is sensitive to radiotherapy and chemotherapy. Here, we found that the transmembrane protein tetraspanin1 (TSPAN1) potently inhibited the in vitro migration and invasion, as well as, the in vivo metastasis of NPC cells via interacting with the IKBB protein. In addition, TSPAN1 was essential in preventing the overactivation of the NF-kB pathway in TSPAN1 overexpressing NPC cells. Furthermore, reduced TSPAN1 expression was associated with NPC metastasis and the poor prognosis of NPC patients. These results uncovered the suppressive role of TSPAN1 against NF-kB signaling in NPC cells for preventing NPC metastasis. Its therapeutic value warrants further investigation.

Immunotherapy in anaplastic thyroid cancer.

Anaplastic thyroid cancer (ATC) is one of the worst human malignancies, with an associated median survival of only 5 months. It is resistant to conventional thyroid cancer therapies, including radioiodine and thyroid-stimulating hormone suppression. Cancer immunotherapy has emerged over the past few decades as a transformative approach to treating a wide variety of cancers. However, immunotherapy for ATC is still in the experimental stage. This review will cover several strategies of immunotherapy and discuss the possible application of these strategies in the treatment of ATC (such as targeted therapy for tumor-associated macrophages, cancer vaccines, adoptive immunotherapy, monoclonal antibodies and immune checkpoint blockade) with the hope of improving the prognosis of ATC in the future.

The incidence and survival analysis for anaplastic thyroid cancer: a SEER database analysis.

BACKGROUND: Thyroid carcinoma is the most common malignant endocrine tumor; the anaplastic thyroid cancer subtype is aggressive and has a poor prognosis. However, there is no effective treatment for this disease. METHODS: This study was analyzed using the Surveillance, Epidemiology, and End Results (SEER) database. Joinpoint regression models, linear regression models, Kaplan-Meier survival curves and Cox regression models were used to study the trends in incidence, survival rate and median survival time and to detect the risk factors affecting prognosis in patients with anaplastic thyroid cancer. RESULTS: While the incidence rate and truncated incidence rate fluctuated slightly over the past 30 years, they were relatively stable and had no obvious upward trend (APC = -0.22 and 0.24, respectively, P>0.05). The median survival was 3.16 months, and the survival rate did not improve significantly (the APC values of the 3-, 6-, 9-, and 12-month survival rates were 0.44, 0.35, -0.23 and -0.86, respectively, P>0.05). After subgroup analysis and survival analysis, it was concluded that the prognosis of the patients might be related to their metastatic stage, surgical status, chemotherapy treatment, age and socioeconomic status at the time of diagnosis (P<0.05). Total thyroidectomy is superior to other methods and is beneficial in prolonging the life of patients and improving the overall survival rate (the median survival was 10 months, and the 6-month survival rate was 59.26%). CONCLUSION: The incidence trend for anaplastic thyroid cancer over the last 30 years was stable, and the survival rate and median survival time were not significantly improved. The prognosis of the patients may be related to their metastatic stage, age, socioeconomic status, surgical status and chemotherapy treatment.

Preoperative Neutrophil Lymphocyte Ratio and Platelet Lymphocyte Ratio Cannot Predict Lymph Node Metastasis and Prognosis in Patients with Early Gastric Cancer: a Single Institution Investigation in China.

In the present study, we aimed at exploring the applied value of preoperative neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in the prediction of lymph node metastasis (LNM) and prognosis in patients with early gastric cancer (EGC). We retrospectively analyzed a total of248 consecutive patients who underwent curative gastrectomy to be identified T1 stage gastric adenocarcinoma between January 1, 2010 and May 1, 2016 in a single institution. According to median preoperative NLR and PLR value, we divided the patients into four groups: high NLR >1.73 and low NLR <1.73, high PLR >117.78 and low PLR <117.78. Furthermore, to evaluate the relationship between preoperative NLR and PLR values, we categorized patients according to cutoff preoperative NLR-PLR score of 2 [high NLR (>1.73) and high PLR (>117.78)], 1 [either high NLR or high PLR], and 0 [neither high NLR nor high PLR], Statistical analyses were conducted using SPSS 20.0 software. The results showed that the preoperative NLR or PLR values, lower or higher, could not predict the LNM in patients with EGC (both P=0.544>0.05). The invasive depth of tumor was significantly correlated with LNM of EGC (P0.001). Kaplan-Meier plots illustrated that preoperative NLR and PLR values were not associated with overall survival (OS) in patients with EGC. It was concluded that the preoperative NLR and PLR may be the predictors for LNM and prognosis in patients with advanced gastric cancer; nevertheless, they cannot predict LNM and prognosis in patients with EGC.

Lymph node mapping with carbon nanoparticles and the risk factors of lymph node metastasis in gastric cancer.

The study aimed to examine the applicability of carbon nanoparticles as a tracer for lymph node mapping and the related factors of lymph node and No.8p subgroup metastasis in patients with gastric cancer. Clinical data of 50 patients with gastric cancer, who had not received treatment preoperatively and underwent gastrectomy in Department of Gastrointestinal Surgery, Wuhan Union Hospital, between October 2014 and August 2015, were retrospectively analyzed. These patients were found to have no distant metastasis preoperatively. Thirty-five out of 50 patients were subjected to lymphatic mapping technique using carbon nanoparticles as the tracer, and the rest 15 cases did not experience the lymphatic mapping and served as controls. The sensitivity, specificity, false positive rate and false negative rate were calculated according to the number of lymph nodes, and the staining and metastasis condition of lymph nodes. The diagnostic value of carbon nanoparticles on metastatic lymph nodes was evaluated. The relationship between the metastasis of lymph nodes or subgroup No.8p lymph nodes and clinicopathologic features was analyzed by χ2-test or Fisher's exact test. All patients underwent D2 surgery (lymph node dissection including all the group 1 and group 2 nodes) plus the dissection of the subgroup No.8p lymph nodes. It was found that the average number of harvested lymph nodes in lymphatic mapping technique group (45.7±14.5) was greater than that in control group (39.2±11.7), but the difference was not significantly different (P=0.138>0.05). The success rate, the accuracy, sensitivity, specificity and false negative rate was 97%, 57%, 28%, 62% and 72% respectively. The metastasis of lymph nodes was correlated to the depth of cancer invasion (T stage) (P=0.004<0.05), and the metastasis of No.8p lymph nodes was correlated to the extent of lymph node involvement (N stage) (P=0.007<0.05). Six cases had lymph node metastasis in subgroup No.8p, and their TNM stages and clinical stages were as follows: T1N2M0 IIA, T3N3M0 IIIB, T4aN3M0 IIIC, T4aN3M0 IIIC, T4aN3M0 IIIC, and T4bN3M0 IIIC. In conclusion, our study indicated that carbon nanoparticles failed to show good selectivity for metastatic lymph nodes; the result of lymphatic mapping does not achieve a satisfactory performance; the incidence of lymph node metastasis may increase, accompanying with the increase of the depth of cancer invasion; No.8p lymph node metastasis tends to occur for gastric carcinoma patients with the extent of lymph node metastasis over N2 stage.