The value of haematological parameters and serum tumour markers for predicting KRAS mutations in 784 Chinese colorectal cancer patients: a retrospective analysis.

BACKGROUND: Identifying the mutation status of KRAS is important for optimizing treatment in patients with colorectal cancer (CRC). The aim of this study was to investigate the predictive value of haematological parameters and serum tumour markers (STMs) for KRAS gene mutations. METHODS: The clinical data of patients with colorectal cancer from January 2014 to December 2018 were retrospectively collected, and the associations between KRAS mutations and other indicators were analysed. Receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of these factors. Univariate and multivariate logistic regression models were applied to identify predictors of KRAS mutations by calculating the odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). RESULTS: KRAS mutations were identified in 276 patients (35.2%). ROC analysis revealed that age, CA12-5, AFP, SCC, CA72-4, CA15-3, FERR, CYFRA21-1, MCHC, and tumor location could not predict KRAS mutations (P = 0.154, 0.177, 0.277, 0.350, 0.864, 0.941, 0.066, 0.279, 0.293, and 0.053 respectively), although CEA, CA19-9, NSE and haematological parameter values showed significant predictive value (P = 0.001, < 0.001, 0.043 and P = 0.003, < 0.001, 0.001, 0.031, 0.030, 0.016, 0.015, 0.019, and 0.006, respectively) but without large areas under the curve. Multivariate logistic regression analysis showed that CA19-9 was significantly associated with KRAS mutations and was the only independent predictor of KRAS positivity (P = 0.016). CONCLUSIONS: Haematological parameters and STMs were related to KRAS mutation status, and CA19-9 was an independent predictive factor for KRAS gene mutations. The combination of these clinical factors can improve the ability to identify KRAS mutations in CRC patients.

Evaluation of a serum tumour marker-based recurrence prediction model after radiofrequency ablation for hepatocellular carcinoma.

BACKGROUND & AIMS: A recent study showed that serum tumour marker-based MoRAL score (11×√protein induced by vitamin K absence-II [PIVKA] +2×√alpha-foetoprotein [AFP]) can reflect both tumour burden and aggressiveness of hepatocellular carcinoma (HCC). This study aimed to evaluate whether baseline MoRAL score could predict tumour recurrence after radiofrequency ablation (RFA) for very-early/early-stage HCC. METHODS: A total of 576 HCC patients who underwent RFA as initial treatment were enrolled from two tertiary referral hospitals (256 in development cohort and 320 in validation cohort). The primary endpoint was recurrence-free survival (RFS) and the secondary endpoints included cumulative risks of intrahepatic distant recurrence (IDR) and extrahepatic metastasis (EM). RESULTS: In the development cohort, MoRAL score was an independent prognostic factor of RFS (P = .02). The optimal cutoff MoRAL score for predicting RFS was 68. Patients with high MoRAL score (>68) showed significantly shorter RFS than did those with low MoRAL score (hazard ratio [HR] = 2.04, P < .001). The 5-year RFS rates were 32.3% and 53.2% in high- and low-MoRAL groups respectively. Risks of both IDR (HR = 1.76, P = .003) and EM (HR = 8.25, P = .006) were also significantly higher in high MoRAL group. These results were reproduced in the validation cohort: RFS (HR = 1.81, P < .001; 5-year RFS rates = 27.7% vs 53.6%) was significantly shorter and risks of IDR (HR = 1.59, P = .003) and EM (HR = 6.19, P = .004) were significantly higher in high MoRAL group. CONCLUSION: A high MoRAL score of >68 was significant a predictive factor of tumour recurrence after RFA for very-early/early-stage HCC. Moreover, it might be warranted to evaluate EM in patients with high baseline MoRAL scores.

The promise of protein glycosylation for personalised medicine.

BACKGROUND: Complex diseases such as cancer are a consequence of numerous causes. State of the art personalised medicine approaches are mostly based on evaluating patients' individual genetic background. Despite the advances of genomics it fails to take individual dynamic influences into account that contribute to the individual and unique glycomic and glycoproteomic "configurations" of every living being. SCOPE OF REVIEW: Glycomic and glycoproteomic-based personalised medicine diagnostics are still in their infancies, however some initial success stories indicate that these fields are highly promising to mediate novel early diagnosis and disease stratification markers, subsequently resulting in improved patient well-being and reduced treatment costs. In this review we not only summarise current protein glycosylation based examples that substantially improve or possess great potential for personalised medicine, but also describe current limitations as well as future perspectives and challenges associated with establishing protein glycosylation aspects for this purpose. MAJOR CONCLUSIONS: Many protein biomarkers currently in clinical use are glycoproteins, however, their glycosylation status is seldom evaluated in a clinical context. To date just few examples have already been successfully translated into clinical practice, making protein glycosylation a highly promising diagnostic target with humongous potential for personalised medicine. GENERAL SIGNIFICANCE: There is an urgent need for markers that enable the establishment of an individualised and optimised patient treatment at the earliest disease stage possible. The glycosylation status of a patient and/or specific marker proteins can provide important clues that result in improved patient management. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc.

Prevalence of CEA, CA 125, and CA 15-3 serum tumour markers in different regions of Saudi Arabia.

OBJECTIVES: To study the prevalence of tumor marker (TM) carcinoembryonic antigen (CEA), cancer antigen 125 (CA 125), and cancer antigen 15-3 (CA 15-3) levels in the Saudi population, based on gender, age, and demographic region, and whether the patients were referred by a hospital or self-referred. METHODS: Retrospective analysis was carried out on 7,019 samples gathered from the Western, Northern, Central, Southern, and Eastern regions of Saudi Arabia between 2021-2022. The TMs were categorized into normal and abnormal levels, according to the reference ranges. Statistical analysis was carried out to assess the relations between variants (age groups, gender, and demographic regions) using the Chi-square test, and their correlations were assessed using Spearman's test. RESULTS: Among all patients, CEA, CA 125, and CA 15-3 levels were found to be significantly correlated with age (p=0.0001). The CEA and CA 15-3 levels increased in both males and females with age. The CA 125 was shown to have an abnormally increased level in males with age. CONCLUSION: Increased levels of CEA, CA 125, and CA 15-3 TMs in the study population were significantly correlated with age. The CEA and CA 15-3 levels were within the normal range, while CA 125 levels were above the normal range in the older male population. These results suggest that the utilization of such TMs is age dependent and would have validity if applied with other parameters.

Serum Levels of MicroRNA-371a-3p for Predicting the Histology of Postchemotherapy Residual Masses of Germ Cell Tumours.

BACKGROUND AND OBJECTIVE: Serum levels of microRNA-371a-3p (M371) represent a novel and sensitive biomarker of germ cell tumours (GCTs). This study analysed the utility of M371 to identify viable cancer (VC) in postchemotherapy (pc) residual masses with the underlying goal of avoiding overtreatment. METHODS: A multicentric, prospective diagnostic study was conducted in 180 GCT patients undergoing pc resection of residual masses. A correlation of M371 measurement results with the histological presence of VC in masses was found. A receiver operating characteristic analysis was performed for exploring the performance characteristics of the test. KEY FINDINGS AND LIMITATIONS: The sensitivity was found to be 68.9%, specificity 99.3%, area under the curve 0.813, positive predictive value 0.969, and negative predictive value 0.905; sensitivity is significantly associated with the percentage of VC in the mass. In specimens with ≤10% VC, there were 33.3% elevated M371 levels as opposed to 85.7% in specimens with >50% VC. Teratoma and somatic-type malignancy do not express M371. A lack of a central pathological review is a limitation. CONCLUSIONS AND CLINICAL IMPLICATIONS: The M371 test can identify 68.9% of patients with VC in pc masses. However, cases with <10% VC in the mass may escape detection. Teratoma does not express M371. The test alone cannot correctly identify patients requiring pc surgery, but it may be a tool for scheduling the extent of surgery. PATIENT SUMMARY: The microRNA-371a-3p (M371) test can identify about two-thirds of patients with viable cancer in residual metastatic masses following chemotherapy for germ cell tumours. Only masses with high percentages of viable cancer cells can be identified, and the histological subtype teratoma remains undetected with the test.

Quantitative analysis of endobronchial elastography combined with serum tumour markers of lung cancer in the diagnosis of benign and malignant mediastinal and hilar lymph nodes.

Purpose: In malignant tumours, elastography and serum tumour markers have shown high diagnostic efficacy. Therefore, we aimed to quantitatively analyse the results of endobronchial elastography combined with serum tumour markers of lung cancer to accurately distinguish benign and malignant mediastinal and hilar lymph nodes. Methods: Data of patients who underwent endobronchial ultrasound-guided transbronchial needle aspiration for mediastinal lymph node enlargement in our hospital between January 2018 and August 2022 were retrospectively collected. The characteristics of quantitative elastography and serum tumour markers were evaluated. Results: We enrolled 197 patients (273 lymph nodes). In the differential diagnosis of benign and malignant mediastinal and hilar lymph nodes, the stiffness area ratio (SAR), strain ratio (SR), and strain rate in lymph nodes were significant, among which SAR had the highest diagnostic value (cut-off value, 0.409). The combination of the four tumour markers had a high diagnostic value (AUC, 0.886). Three types of quantitative elastography indices combined with serum tumour markers for lung cancer showed a higher diagnostic value (AUC, 0.930; sensitivity, 83.5%; specificity, 89.3%; positive predictive value, 88.1%; negative predictive value, 85%) (p < 0.05). In the differential diagnosis of pathological types of lung cancer, different quantitative elastography indicators and serum tumour markers for lung cancer have different diagnostic significance for the differential diagnosis of lung cancer pathological types. Conclusion: The quantitative analysis of endobronchial ultrasound elastography combined with tumour markers can improve the diagnosis rate of benign and malignant mediastinal and hilar lymph nodes, help guide the puncture of false negative lymph nodes, and reduce the misdiagnosis rate.

Development and validation of MMR prediction model based on simplified clinicopathological features and serum tumour markers.

BACKGROUND: Although simplified clinicopathological features and serum tumour markers (STMs) were reported to be associated with the status of mismatch repair (MMR) in colorectal cancer (CRC) patients, their predictive value alone or in combination for MMR status remains unknown. METHODS: A retrospective analysis of 3274 participants with MMR testing and STMs measurements from two institutions was conducted. The prediction model was developed in the primary cohort that consisted of 1964 participants. Best subset regression was applied to select the most useful predictors from the primary dataset. The performance of the nomogram was evaluated with respect to its calibration, discrimination, and clinical usefulness. External validation was performed in an independent validation cohort of 1310 consecutive CRC patients. FINDINGS: Among the ten simplified clinicopathological features, seven variables were selected as the best subset of risk factors to develop pathology-based model, including age, tumour diameters, histology, tumour location, perineural invasion, the number of sampled lymph nodes (LNs) and positive LNs. The model showed good calibration and discrimination, with an AUC of 0.756 (95% CI, 0.722 to 0.789) in the primary cohort and 0.754 (95% CI, 0.715 to 0.793) in the validation cohort. After the addition of CEA and CA 72-4, the performance of pathology-based model was significantly improved in in both the primary cohort (AUC: 0.805 (0.774-0.835) vs. 0.756 (0.722-0.789), P < 0.001) and validation cohort (AUC: 0.796 (0.758-0.835) vs. 0.754 (0.715-0.793), P < 0.001). The results of decision curve analysis revealed that using our models to predict the status of MMR would add more benefit than either the detect-all-patients scheme or the detect-none scheme. INTERPRETATION: The models based on simplified clinicopathological features alone or in combination with STMs can be conveniently used to facilitate the postoperative individualized prediction of MMR status in CRC patients.

Isolated involuntary weight loss: Epidemiology and predictive factors of malignancy. / Pérdida de peso involuntaria aislada: epidemiología y factores predictivos de malignidad.

BACKGROUND AND OBJECTIVES: The aims of the study were to analyse the epidemiology, prognostic and predictive factors of malignant disease on isolated involuntary weight loss (IIWL) and to know the effectiveness of the quick diagnosis unit in the evaluation of the process. MATERIAL AND METHODS: Prospective observational study realised from 2006 to 2015 of all patients who were evaluated with IIWL in the quick diagnosis unit. Demographic, clinical, diagnostic and evolutive variables were analysed. Through the analysis of logistic regression, predictive factors of malignant disease and prognostic factors were identified. RESULTS: Of the 533 registered patients, 55.1% were≥65 years old. The diagnostics were: non-neoplastic organic disorders in 214 patients (40.2%), psychiatric disorders in 144 (27%), cancer in 81 (15.2%) and unknown cause in 94 (17.6%). In 66.7% of the patients with cancer, there was an increase of serum tumour markers (STM). Being over 60 (OR: 2.57; 95% CI: 1.27-5.77; P=.01) %), male (OR: 3.23; 95% CI: 1.52-6.87; P=0.002), increase of an STM (OR: 2.38; 95% CI: 1.17-4.8; P=0.016) and more than one STM (OR: 6.51; 95% CI: 2.62-16.13; P=0.000) were identified as predictive factors of malignancy. Mortality was 14.2%; the diagnosis of cancer (OR: 47.61; 95% CI: 20.76-109.19; P=0.000) was identified as a prognostic factor. CONCLUSIONS: IIWL is a clinical syndrome that requires a study with a sequential protocol and follow-up. STM were identified as predictive factors of malignancy.

Probing Tumour Proteostasis and the UPR with Serum Markers.

Tumour proteostasis and the unfolded protein response (UPR) are emerging drivers of tumour progression and important determinants of clinical efficacy of cancer therapy. Recent findings indicate that they also regulate the production of protein tumour markers. Here, we discuss how this new knowledge opens up new perspectives for cancer therapeutics.