Although blood autoantibodies were initially associated with autoimmune diseases, multiple evidence have been accumulated showing their presence in many types of cancer. This has opened their use in clinics, since cancer autoantibodies might be useful for early detection, prognosis, and monitoring of cancer patients. In this review, we discuss the different techniques available for their discovery and validation. Additionally, we discuss here in detail those autoantibody panels verified in at least two different reports that should be more likely to be specific of each of the four most incident cancers. We also report the recent developed kits for breast and lung cancer detection mostly based on autoantibodies and the identification of novel therapeutic targets because of the screening of the cancer humoral immune response. Finally, we discuss unsolved issues that still need to be addressed for the implementation of cancer autoantibodies in clinical routine for cancer diagnosis, prognosis, and/or monitoring.

Neuroendocrine tumors (NETs) of the appendix are rare and are often discovered incidentally during surgery for acute appendicitis or other unrelated conditions (Modlin et al. in Gastroenterology 128:1717-1751, 2005, Alsaad et al. in Oncol Rep 16:1105-1109, 2006, Frilling et al. in Lancet Oncol 15:e8-e21, 2014). These tumors can range from asymptomatic incidental findings to clinically significant tumors with metastases (Alsaad et al. in Oncol Rep 16:1105-1109, 2006, Gomes et al. in World J Emerg Surg 10:60, 2015, Paiva et al. in Eur J Cancer 38:702-705, 2002, Burke et al. in Am J Surg Pathol. 9:661-674, 1985). This case report presents a rare case of a NET of the appendix presenting as acute appendicitis.

A 23-year-old male presented with right lower quadrant abdominal pain, nausea, and vomiting for 2 days. A CT scan revealed a mucocoele of the appendix. The patient underwent laparoscopic appendectomy, and the appendix was sent for histopathological examination. The final pathological report confirmed a NET of the appendix with a Ki-67 index of 1% and no lymphovascular invasion. Due to tumor invasion to the cecum and its large size (3-4 cm), the patient underwent right hemicolectomy. The final histopathology report of the resected specimen confirmed the diagnosis of NET of the appendix.

The clinical diagnosis of NETs of the appendix can be challenging due to their rarity and non-specific presentation. Symptoms of NETs of the appendix can mimic those of acute appendicitis, making it difficult to differentiate between the two conditions. Imaging studies, such as CT scans, can provide valuable information about the size and location of the tumor (Gomes et al. in World J Emerg Surg 10:60, 2015, Maggard et al. in Ann Surg 240:117-122, 2004, Burke et al. in Am J Surg Pathol. 9:661-674, 1985, Frilling et al. in Lancet Oncol 15:e8-e21, 2014). However, the definitive diagnosis is made through histopathological examination of the resected specimen. The treatment of NETs of the appendix depends on factors such as the size, location, and grade of the tumor. Small tumors confined to the appendix with no lymph-vascular invasion can be treated with appendectomy alone, while larger tumors or those that have spread beyond the appendix may require more extensive surgery, such as right hemicolectomy (Gomes et al. in World J Emerg Surg 10:60, 2015, Mestier et al. in Dig Liver Dis 52:899-911, 2020, Maggard et al. in Ann Surg 240:117-122, 2004, Burke et al. in Am J Surg Pathol. 9:661-674, 1985, Frilling et al. in Lancet Oncol 15:e8-e21, 2014, Pavel et al. in Neuroendocrinology 103:172-185, 2016). In some cases, additional treatments such as chemotherapy or radiation therapy may be recommended.

This case report emphasizes the importance of considering NETs of the appendix in the differential diagnosis of acute appendicitis. Imaging studies can provide valuable information, but the definitive diagnosis is made through histopathological examination. The treatment approach for NETs of the appendix depends on various factors and requires a multidisciplinary approach for optimal management.

Hepatocellular carcinoma (HCC) exerts huge effects on the health burden of the world because of its high mortality and poor prognosis. HCC is often clinically detected late in patients. If HCC could be detected and treated earlier, the survival rate of patients will be greatly improved. Therefore, identifying specific biomarkers is urgent and important for HCC. The liver is also recognized as an immune organ. The occurrence of HCC is related to exacerbation of immune tolerance and/or immunosurveillance escape. The host immune system plays an important role in the recognition and targeting of tumor cells in cancer immunotherapy, as can be seen from the clinical success of immune checkpoint inhibitors and chimeric antigen receptor (CAR) T cells. Thus, there is a pressing medical need to discover immunodiagnostic biomarkers specific to HCC for understanding the pathological mechanisms of HCC, especially for immunotherapy targets. We have reviewed the existing literature to summarize the immunodiagnostic markers of HCC, including autoantibodies against tumor-associated antigens (TAAs) and exosomes, to provide new insights into HCC and early detection of this deadly cancer.

Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor of the digestive system worldwide, especially in China. Due to the lack of effective early detection methods, ESCC patients often present at an advanced stage at the time of diagnosis, which seriously affects the prognosis of patients. At present, early detection of ESCC mainly depends on invasive and expensive endoscopy and histopathological biopsy. Therefore, there is an unmet need for a non-invasive method to detect ESCC in the early stages. With the emergence of a large class of non-invasive diagnostic tools, serum tumor markers have attracted much attention because of their potential for detection of early tumors. Therefore, the identification of serum tumor markers for early detection of ESCC is undoubtedly one of the most effective ways to achieve early diagnosis and treatment of ESCC. This article reviews the recent advances in the discovery of blood-based ESCC biomarkers, and discusses the origins, clinical applications, and technical challenges of clinical validation of various types of biomarkers.

Esophageal squamous cell carcinoma (ESCC) and esophagogastric junction adenocarcinoma (EGJA) are the two main types of gastrointestinal cancers that pose a huge threat to human health. ESCC remains one of the most common malignant diseases around the world. In contrast to the decreasing prevalence of ESCC, the incidence of EGJA is rising rapidly. Early detection represents one of the most promising ways to improve the prognosis and reduce the mortality of these cancers. Current approaches for early diagnosis mainly depend on invasive and costly endoscopy. Non-invasive biomarkers are in great need to facilitate earlier detection for better clinical management of patients. Tumor-associated autoantibodies can be detected at an early stage before manifestations of clinical signs of tumorigenesis, making them promising biomarkers for early detection and monitoring of ESCC and EGJA. In this review, we summarize recent insights into the iden-tification and validation of tumor-associated autoantibodies for the early detection of ESCC and EGJA and discuss the challenges remaining for clinical validation.

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide. The survival rate after the onset of symptoms is generally less than one year for the late presentation of HCC, and reliable tools for early diagnosis are lacking. Therefore, novel biomarkers for the early detection of HCC are urgently required. Recent studies show that the abnormal release of proteins by tumor cells can elicit humoral immune responses to self-antigens called tumor-associated antigens (TAAs). The corresponding autoantibodies can be detected before the clinical diagnosis of cancer. Therefore, there is growing interest in using serum autoantibodies as cancer biomarkers. In this review, we focus on the advances in research on autoantibodies against TAAs as serum biomarker for detection of HCC, the mechanism of the production of TAAs, and the association of autoantibodies with patients' clinical characteristics.