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CN-121978336-A - Application of HER-2 combined tertiary lymphoid structure in diagnosis and treatment of mixed hepatocyte-cholangiocarcinoma

CN121978336ACN 121978336 ACN121978336 ACN 121978336ACN-121978336-A

Abstract

The invention discloses application of HER-2 combined tertiary lymphoid structure in diagnosis and treatment of mixed hepatocellular carcinoma-cholangiocarcinoma. The prognosis evaluation system and the treatment decision mode constructed based on the detection of HER-2 are beneficial to establishing a standard cHCC-CCA prognosis system, and the detection of HER-2 can be directly connected with the existing pathological examination flow by adopting a clinical conventional immunohistochemical method, so that the clinical transformation threshold is effectively reduced, and the clinical practicability and operability are remarkable. At the same time, the expression level of HER-2 can reflect whether a patient can directly benefit from adjuvant chemotherapy, and thus can rapidly generate treatment regimens for different patients after pathological examination. Moreover, the invention also discloses the association of HER-2 and tumor immune microenvironment, and provides a new idea for developing HER-2 and TLS combined prognosis products and targeted drug combined immunotherapy strategies.

Inventors

  • GONG WENCHEN
  • SUN YAN
  • CHEN LU
  • WEI YUKUN

Assignees

  • 天津市肿瘤医院（天津医科大学肿瘤医院）

Dates

Publication Date
20260505
Application Date
20260210

Claims (10)

  1. Application of HER-2 expression level detection reagent in preparing mixed hepatocellular-cholangiocellular carcinoma prognosis evaluation product.
  2. Application of HER-2 expression level detection reagent combined with tertiary lymphoid structure abundance detection reagent in preparing mixed hepatocellular-cholangiocellular carcinoma prognosis evaluation product.
  3. Use of a reagent for detecting HER-2 expression level in the preparation of a product for predicting the benefit of mixed hepatocyte-cholangiocarcinoma adjuvant chemotherapy, wherein a patient negative for HER-2 is suitable for adjuvant chemotherapy and a patient positive for HER-2 is not suitable for adjuvant chemotherapy.
  4. 4. A pharmaceutical composition for treating mixed hepatocellular-cholangiocarcinoma, comprising a HER-2 targeting drug for treating a mixed hepatocellular-cholangiocarcinoma patient whose HER-2 is positive and an adjuvant chemotherapy drug for treating a mixed hepatocellular-cholangiocarcinoma patient whose HER-2 is negative.
  5. 5. The pharmaceutical composition of claim 4, further comprising an immunotherapeutic agent for treating a mixed hepatocyte-cholangiocarcinoma patient positive for HER-2 and having a high tertiary lymphoid structure score.
  6. 6. A hybrid hepatocellular-cholangiocellular carcinoma prognosis device, comprising: the collection unit is used for collecting the expression level of HER-2 in the tumor tissue sample; an analysis unit for determining a prognosis of the mixed hepatocellular-cholangiocarcinoma based on the expression level of HER-2, wherein HER-2 is positive for a better prognosis and HER-2 is negative for a worse prognosis; And the output unit is used for outputting a prognosis result.
  7. 7. The hybrid hepatocellular carcinoma prognostic device according to claim 6, wherein the collection unit is further configured to collect the abundance of tertiary lymphoid structures in the tumor tissue sample, with a better prognosis if HER-2 is positive and has tertiary lymphoid structures.
  8. 8. A hybrid hepatocyte-cholangiocellular carcinoma assisted chemotherapy benefit prediction device, comprising: the collection unit is used for collecting the expression level of HER-2 in the tumor tissue sample; an analysis unit for determining whether the mixed hepatocyte-cholangiocarcinoma is suitable for receiving adjuvant chemotherapy based on the expression level of HER-2, wherein adjuvant chemotherapy is suitable if HER-2 is negative; and the output unit is used for outputting an auxiliary chemotherapy benefit prediction result.
  9. 9. A hybrid hepatocyte-cholangiocellular carcinoma treatment regimen generating device, comprising: the collection unit is used for collecting the expression level of HER-2 in the tumor tissue sample; an analysis unit for generating a treatment regimen based on the expression level of HER-2, suggesting an adjuvant chemotherapy if HER-2 is negative; And the output unit is used for outputting the treatment scheme.
  10. 10. A storage medium comprising a stored computer program, wherein the computer program, when run, controls a device in which the storage medium is located to perform a method of mixed hepatocellular-cholangiocarcinoma prognosis and/or treatment plan generation, the method comprising the steps of: Obtaining HER-2 expression level and tertiary lymphoid structure score of a tumor tissue sample; prognosis is based on the HER-2 expression level and tertiary lymphoid structure score, wherein if HER-2 expression level is positive and has a prognosis with a better tertiary lymphoid structure, a worse prognosis is associated with a negative HER-2 expression level, and/or Generating a treatment scheme based on the HER-2 expression level and the tertiary lymphoid structure score, wherein if the HER-2 expression level is negative, the treatment scheme adopts auxiliary chemotherapy, if the HER-2 expression level is positive and the tertiary lymphoid structure score is 0 point, the treatment scheme adopts only HER-2 targeting drugs, and if the HER-2 expression level is positive and the tertiary lymphoid structure score is 1-3 points, the treatment scheme is combined with HER-2 targeting drugs and immunotherapeutic drugs; Output prognosis results and/or treatment regimens.

Description

Application of HER-2 combined tertiary lymphoid structure in diagnosis and treatment of mixed hepatocyte-cholangiocarcinoma Technical Field The invention relates to the technical field of tumor molecular markers, in particular to application of HER-2 combined tertiary lymphoid structure in diagnosis and treatment of mixed hepatocyte-cholangiocarcinoma. Background Hybrid hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary hepatic malignancy characterized by the histological appearance of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). At present, the treatment strategy of cHCC-CCA is mostly based on clinical experience of hepatocellular carcinoma or intrahepatic cholangiocarcinoma, and surgical excision is the only radical treatment means, but the surgical indication is strict and is only applicable to a few patients. CHCC-CCA has extremely poor prognosis, the median total survival time after surgical excision is only 32 months, the total survival rate in 5 years is between 23.6% and 36.4%, and the postoperative recurrence rate is high. At present, a targeted prognosis evaluation index is lacking, and the traditional tumor prognosis evaluation mode depends on TNM (tumor necrosis factor) stage, vascular invasion, tumor size, lymph node metastasis and other indexes, and the prognosis evaluation accuracy of cHCC-CCA patients is insufficient, so that the postoperative survival condition of the patients can not be accurately predicted. Furthermore, although postoperative adjuvant chemotherapy has been demonstrated to have survival benefits in a variety of tumors such as gastric cancer, breast cancer, intrahepatic cholangiocarcinoma, there is currently no clear consensus on whether or not to employ adjuvant chemotherapy after the operation for cHCC-CCA patients. Some patients may receive additional medical burden and adverse reactions due to blindly receiving chemotherapy, while some potentially benefited patients fail to get effective treatment in time. The inventor team in patent CN120766967A discloses a hybrid liver cancer prognosis model, which combines traditional clinical pathology features and immune microenvironment indexes to construct a nomogram, has good cHCC-CCA prognosis prediction performance, can provide postoperative auxiliary chemotherapy decisions for patients with different risk levels, and proves the key roles of the two tumor immune microenvironment indexes of CD8 and FOXP3 in cHCC-CCA prognosis. However, there is no independent prognostic indicator for cHCC-CCA at this stage and the decision basis for prognosis and adjuvant therapy is very limited. Therefore, the active search for specific cHCC-CCA biomarkers, the establishment and perfection of a standardized prognosis evaluation system and a treatment decision mode aiming at cHCC-CCA, are of great significance. Disclosure of Invention Human epidermal growth factor receptor 2 (HER-2) is a receptor tyrosine kinase located on the cell surface. In healthy cells, after growth factors (ligands) bind to other receptors of the HER family, HER-2 will pair with them (form dimers), signaling into the cell, regulating normal growth, division and repair of the cell. As an Epidermal Growth Factor Receptor (EGFR) family member, HER-2 is currently established as a prognostic factor and a therapeutic target in various solid tumors such as breast cancer, gastric cancer and the like. However, the expression pattern of HER-2 in cHCC-CCA, prognostic significance, and predictive value of adjuvant chemotherapy efficacy are not well known. According to the application, through analysis of 87 cases cHCC-CCA patients clinical samples, it is found that HER-2 expression is an independent protection factor of total postoperative survival (OS) of cHCC-CCA patients, and the total survival of HER-2 positive patients is longer than that of HER-2 negative patients, so that cHCC-CCA patients with different prognosis risks can be effectively distinguished by HER-2. In the present application, it was also demonstrated that HER-2 negative patients could benefit from adjuvant chemotherapy regimens by comparing the effect of adjuvant chemotherapy on total survival to different HER-2 expression sets and validating with PSM, but positive patients did not need to receive adjuvant chemotherapy regimens. Further, the present application analyzed the correlation between HER-2 and Tertiary Lymphoid Structure (TLS) and found that HER-2 positivity was significantly positively correlated with TLS score, i.e., TLS was more enriched in tissues in HER-2 positive patients. Moreover, the accuracy of the HER-2 positive performance as an independent prognostic index is more prominent in patients with higher TLS abundance, so that the HER-2 and tertiary lymphoid structures can be combined to further improve the prognostic capacity of cHCC-CCA, and a treatment strategy combining a HER-2 targeting drug and immunotherapy is constructed based on the correlatio